Welcoming you for any type of article submission for the upcoming issue on/before February 26, 2021.


Research Article
Volume 2 Issue 4 - 2016
Multidrug Resistant Tuberculosis Cure Predictors
Vinod Namana1,2*, and Pankaj Mathur3
1Department of Cardiology, Maimonides Medical Center, Brooklyn, USA
2Department of Public Health, Icahn School of Medicine at Mount Sinai, USA
3University of Arkansas for Medical Sciences, Little Rock, AR, USA
*Corresponding Author: Vinod Namana, Fellow in Cardiovascular Medicine, Maimonides Medical Center, Department of Cardiology, 4802 10th avenue, Brooklyn, NY 11219, USA.
Received: May 19, 2016; Published: May 31, 2016
Citation: Vinod Namana and Pankaj Mathur. “Multidrug Resistant Tuberculosis Cure Predictors”. EC Bacteriology and virology Research 2.4 (2016): 154-164.
Abstract
Many parts of the world face a new challenge to control tuberculosis epidemic with the emergence of Multi Drug Resistant Tuberculosis (MDR-TB) and Extensive Drug Resistant Tuberculosis (XDR-TB). We analyzed the data from a prospective study of patients with MDR-TB & XDR-TB treated in Medicines Sans Frontieres (MSF) hospitals in Armenia to identify patients and treatment characteristics that predict cure of MDRTB and XDR-TB. Of 350 patients, 197 (56.4 %) had a history of alcohol use, 130 (37.1%) history of being in prison and 64 (18.4%) were injecting drug users. Out of 350 patients, 37 (10.6 %) were cured and 313 (89.4) were not cured. In multivariate analysis, success was positively associated with treatment duration (OR = 1.1, p = 0.003), moderate alcohol use (OR= 3.5, p = 0.01) and negatively associated with injection drug use (OR = 0.66, p = 0.02) and trend towards negative association with excessive alcohol use (OR= 6.26x10-9, p = 0.99). The proportion of patients achieved cure is very low. Results suggest that, longer the treatment duration and moderate alcohol use better the treatment outcome. Patients with injection drug use had a poor treatment outcome. Excessive alcohol use showed trend towards poor treatment outcome.
Keywords: Multi Drug Resistant Tuberculosis (MDR-TB); Extensive Drug Resistant Tuberculosis (XDR-TB); Tuberculosis (TB); Treatment outcome; Alcohol; IV drug use
Introduction
The world now faces a new challenge of tuberculosis (TB) epidemic, due to emergence of Multi Drug Resistant Tuberculosis (MDR-TB) and Extensive Drug Resistant Tuberculosis (XDR-TB) [1,2]. MDR-TB is defined as infecting isolates that are resistant in vitro to isoniazid (H) and rifampicin (R), XDR-TB is defined as resistance to any fluoroquinolone, and 1of 3 injectable second-line drugs (capreomycin, kanamycin and amikacin) [1,3]. According to the Global Tuberculosis 2014 report by World Health Organization (WHO) there were an estimated 480,000 (range: 350,000 - 610,000) new cases of MDR-TB worldwide, and approximately 210 000 (range: 130,000 - 290,000) deaths from MDR-TB [1]. In 2013, WHO estimated that 3.5% of all new TB cases and 20.5% of previously treated cases have MDR-TB [1]. By 2013, XDR-TB has been reported in at least 100 countries and 9% of MDR-TB cases have XDR-TB [1]. WHO estimated that, the proportion of MDR-TB diagnosed of new TB cases is 9.4% and previously treated TB cases is 43% in Armenia [1].
The success rate of MDR-TB treatment globally is low; 48% reported in Global tuberculosis 2014 report [1], 54% reported by Ahuja SD., et al. [4], 62% reported by Johnston., et al. [5] and 64% reported by Orenstein., et al. [6]. MDR-TB success is low as there are limited treatment options and several other factors affecting the cure. To cure an MDR-TB patient, it takes 18 - 24 months with second-line drugs (SLDs), which are less efficacious, more toxic, less tolerated and considerably more expensive [1,7,8]. The other factors that affect the MDR-TB cure are co-infection with HIV [9-13], social factors such as alcohol [7,9,12,14,15] and intravenous drug abuse [10]; socioeconomic factors like poverty and unemployment [16,17]; advanced disease, prior treatment, treatment default [18], resistance to fluroquinolones [9,13-15] positive acid-fast bacilli (AFB) smear at the start of treatment, absence of early culture conversion, number of drugs in the regimen [5,6,19-21] and programmatic factors such as poor provider communication and barriers to accessing care [22]. We analyzed the data from a prospective study of patients with MDR-TB & XDR-TB treated in Medicines Sans Frontiers (MSF) hospitals in Armenia who received an individualized treatment regimen (ITR) based on drug sensitivity testing (DST) results to identify patients and treatment characteristics that predict cure of MDR-TB and XDR-TB and to determine if there are specific identifiable groups who are at increased risk of failure to cure.
Materials
Study settings
This was an original study of Medicines Sans Frontieres organization. This is an observational prospective cohort study of 350 patients with MDR-TB & XDR-TB treated in MSF hospitals in Armenia. Tuberculosis database program: Epi Info (Version-6) was used to have universal data registry and ensure to have correct and updated information in all MDR-TB program centers. Data was collected in Armenia Hospitals from 2001 to 2008. This study was conducted by MSF and WHO Green light committee approved it. Informed consent was taken from patients before they were included in the study. Analysis of this study data was also approved by Public Health Department at Icahn School of medicine at Mount Sinai, New York.
Patient selection process
The aim of a MDR-TB treatment program was to make treatment accessible to as many patients who needed treatment. However there were some criteria’s and preliminary steps before they were included into the program. Decision to include or exclude a patient, was a team decision and is discussed by the physician with the other care givers such as nurse, health educator, social worker and the psychiatrist.
Inclusion and exclusion criteria Included only those patients who meet the geographic criteria of living in the region, after undergoing through a preliminary introduction and agreed for the treatment. In preliminary introduction patients were informed about the disease process, length of the treatment, directly observed treatment, need for hospitalization, side effects, expected outcomes and the need of follow-up. Any questions or difficulties experienced by the patient were addressed. Patients are required to commit to adhere to the treatment and complete the course of treatment. Patients who have severe co-existing illnesses and who seemed to not tolerate the second line Anti-TB medications, in terminal clinical conditions were excluded. The patient’s family is also implicated in supporting the patient and should be involved in the preliminary information sessions. Factors that could result in poor or difficult adherence for the patient, such as addictions (drug, alcohol) and with previous history of poor treatment adherence, coping mechanisms and support systems were discussed before inclusion. Female patients should agree together with their partner to use a reliable method of contraception to avoid pregnancy during the full course of treatment. Second line drugs reduce the serum concentration of oral contraceptives therefore injectable contraception is preferred method. Pre-existing and severe co-existing illness such as renal and hepatic insufficiency, uncontrolled seizure disorder, or known allergies to second-line drugs, which could prevent the managing physician from prescribing an effective second-line treatment regimen were excluded. Program ensured prison patients to have continuity of treatment.
General treatment principles All patients received an individualized treatment regimen (ITR) based on DST results. An Empiric Treatment Regimen (ETR) is used on a temporary basis for certain suspect cases until full DST results become available. Treatment is given under direct observation (DOT). Treatment is initiated with small doses of each drug and increased to the planned dose over 3 to 10 days. Maximum doses of second-line drugs are used whenever possible, with immediate and aggressive treatment of side effects. Therapy is given 6-7 days per week and up to twice daily; no intermittent therapy with second-line drugs is given during either intensive or continuation phase except for parenteral agents, which may be given 3 times weekly when side effects such as renal insufficiency arise. When treatment fails or a relapse occurs, the original regimen is continued with addition of 2 new drugs until new susceptibility data are obtained. The minimum treatment duration of MDR-TB treatment is 21-24 months or 18 months after the patient becomes permanently smear and culture negative, whichever is longer.
Criteria for treatment interruption included 1. Impossible to continue proper treatment due to intolerance to second-line drugs 2. The physician may also determine after 6 to 12 months in case of unfavorable evolution, using all clinical and microbiologic evidence available, that further therapy is futile and only supportive care should be offered. 3. The feasibility and the benefit of the surgical option have to be considered before proposing the permanent interruption of treatment. 4. Poor adherence to treatment (frequent treatment interruptions, addictions) Aggressive, disruptive or criminal behavior during treatment could be considered as dismissal criteria.
Case definitions for end of treatment outcomes
Cured: An MDR-TB patient who has completed treatment and has been consistently culture-negative (with at least five results) for the final twelve months of treatment. If only one positive culture is reported during that time and there is no concomitant clinical evidence of deterioration, a patient may still be considered cured, provided that this positive culture is followed by a minimum of three consecutive negative cultures, taken at least 30 days apart.
Completed: An MDR-TB patient who has completed treatment but does not meet the definition for cure due to lack of bacteriological results (i.e., fewer than five cultures were performed in the final twelve months of therapy).
Death: An MDR-TB patient who dies for any reason during the course of MDR-TB treatment.
Treatment failure: Treatment will be considered to have failed if two or more of the five cultures recorded in the final twelve months are positive, or if any one of the final three cultures is positive. Treatment will also be considered to have failed if a clinical decision has been made to terminate treatment early due to poor response or adverse events.
Treatment default: An MDR-TB patient whose MDR-TB treatment was interrupted for two or more consecutive and also includes the patients removed from treatment by physicians.
Transfer out: An MDR-TB patient who has been transferred to another reporting and recording unit and for whom the treatment outcome is unknown.
Still on treatment: Patient still in treatment at the time of the cohort analysis.
Statistics
To look for correlations between the patients and treatment characteristics that predict cure of MDR-TB and XDR-TB, we used univariate student t-test and chi-square tests. An independent-samples t-test was conducted to compare between the success and failure groups with age, treatment duration, days to smear conversion, days to culture conversion, days to end hospitalization, days to end injection phase, Previous DOTS treatment, Previous DOTS Plus treatment, number of people living in the same house, and number of children living in the same house. A chi-square test was conducted to compare between the success and failure groups with risk factors (nominal variables) such as previous TB treatment, drug sensitivity testing, marital status, employment status, ever been in prison, injection drug user, prostitution, homeless, healthcare worker, migrant worker, traveler (out of Armenia), previous contact with MDR-TB case, tobacco use and alcohol use.
Treatment outcome variables were categorized into a dichotomous variable as success and failure. Success included all cured cases and all other treatment outcomes such as treatment completed, failed, default (whose treatment was interrupted for 2 consecutive months or more), transfer out and unknown status were included in failure group. Bivariate analysis using Independent t-test for continuous variables and chi-square for discrete variables was performed taking success and failure as dependent variables and other variables as independent or covariate variables. To check out the hypothesis, we did logistic regression. All values are expressed as mean ± SD or valid percentages (%). All statistical analyses were achieved using the Statistical Package for Social Sciences (SPSS) 21.0 software (SPSS Inc., Chicago, Illinois). Missing data were not replaced or imputed. A P value < .05 was considered significant.
Results
Observation data for 350 patients from 2001 to 2008 were analyzed. There were 282, (80.6%) males and 68 (19.4%) females; mean age was 38 ± 13 years. Most patients were unemployed 255 (73.1%), lived in their own homes 338 (97.7%), lived with 3 or more people(range 1-9) and had one child in their house (range 0-5). Sixty-four (18.4%) have history of intravenous drug use (IDU) and 130 (37.1%) have history of being in prison, 197 (56.0%) had a history of alcohol use -162 (46%) moderate, 35(10%) excessive, and 218 (62.3%) had a history of tobacco use. Of all 350 patients, 78 (22.6%) reported previous contact with MDR-TB patients (Table 1).
Variables Value ± SD or Percentage
Age (years) 38 ± 13
Male (%) 80.6
Female (%) 19.4
Migrant worker (%) 3.5
Health care worker (%) 0.9
Homeless (%) 2.3
Marital status (%)
Married 50.7
Living together 0.9
Single 36
Divorced 6.9
Widowed 4
Separated 1.4
Employment status (%)
Employed 16.3
Pensioner 3.2
Student 2.3
Unemployed 73.1
Household 4
Other 1.1
Tobacco use (%) 62.6
Alcohol use (%) 56.4
Alcohol Severity (%)
None 43.6
Moderate 46.4
Excessive 10
Injection drug user (%) 18.4
Prostitution (%) 0.3
Ever been in prison (%) 37.2
Traveller (out of Armenia) (%) 10.7
Contact with MDR-TB case (%) 22.6
Number of people living in the same house 3 ± 1.8
Number of children less than 15 living in the same house 1 ± 1.02
SD: Standard deviation
Table 1: Patient characteristics.
The mean treatment duration was 12.75 ± 9.1 (1 - 44.9) months. The average number of days to initial smear conversion was 114.1 ± 118.4 days, number of days to initial culture conversion was 112.2 ± 115.03, number of days to end of hospitalization phase was 140.31 ± 133.36 and number of days to end of injection phase was 240.04 ± 118.7. 344 (98.3%) patients reported to previous TB treatment, the average number of times the patient has received DOTS treatment is 2.07 ± 1.6, the average number of times the patient has received DOTS PLUS treatment is 0.12 ± 0.4 and 90.8% have not received DOTS PLUS treatment previously. On Drug Sensitivity Testing, before the start of treatment 284 (93.4%) were resistant to Isoniazid (H), 239 (79.7%) were resistant to Rifampin (R), 243 (80.7%) were resistant to Ethambutol, 73 (47.7%) were resistant to Pyrazinamide (P) and 265 (89.2%) were resistant to Streptomycin (S) (Table 2).
Variables Value ± SD or Percentage
Treatment duration (months) 12.75 ± 9.1
Days to smear conversion 114.1 ± 118.4
Days to culture conversion 112.2 ± 115.03
Days to end hospitalization 140.3 ± 133.4
Days to end injection phase 240.04 ± 118.7
Previous TB treatment (%) 98.3
No. of previous DOTS treatment 2.07 ± 1.6
No. of previous DOTS treatment (%)
0 2
1 43.1
2 28.4
3 13.8
4 7.5
5 2.6
6 1.1
7 0.6
No. of previous DOTS Plus treatment 0.12 ± 0.4
No. of previous DOTS Plus treatment (%)
0 90.8
1 6.9
2 2
3 0.3
Treatment interruption (%) 0.9
Drug Sensitivity Testing (DST) (%)
Isoniazid (H)  
Resistant 93.4
Sensitive 4.9
Rifampin (R)  
Resistant 79.7
Sensitive 19.7
Ethambutol (E)
Resistant 80.7
Sensitive 18.9
Pyrazinamide (Z)
Resistant 47.7
Sensitive 51.6
Streptomycin (S)
Resistant 89.2
Sensitive 10.8
SD: Standard deviation
Table 2: Patient management characteristics.
Assessment of treatment outcomes showed that 37(10.6 %) patients were cured, 36 (10.3 %) completed therapy, 31 (8.9%) died, 13 (3.7 %) treatment failed, 64 (18.3 %) defaulted and 29 (8.3 %) were transferred out (Table 3).
Treatment outcome Percentage
Cured 10.6
Completed 10.3
Death 8.9
Failure 3.7
Default 18.3
Transfer out 8.3
Unknown 39.7
Table 3: Treatment outcomes.
In bivariate analysis followed by logistic regression, success was positively associated with treatment duration (OR = 1.1, 95% CI (1.03 - 1.18), p = 0.003), moderate alcohol use (OR= 3.5, 95% CI (1.34 - 9.15), p = 0.01 and negatively associated with injection drug use (OR = 0.66, 95% CI (0.006 - 0.7), p = 0.02) and trend towards negative association with excessive alcohol use (OR= 6.26x10-9, 95% CI (0.0 - ∞), p = 0.99 (Table 4 and 5).
  Success Failure    
  n Mean SD n Mean SD P - Value 95% CI
Age 37 38.16 12.04 313 38.27 13.01 0.96 -4.5 - 4.3
Treatment duration (months) 37 22.35 6.83 313 11.61 8.68 <0.001 7.8 -13.6
Days to smear conversion 32 121.3 89.57 143 107.87 119.6 0.55 -30.8 -57.7
Days to culture conversion 35 104.4 69.20 129 108.95 119.4 0.83 -46.2- 37.2
Days to end hospitalization 33 231.2 168.50 232 121.25 128.5 <0.001 60.9 - 159.1
Days to end injection phase 36 236.3 104.47 145 241.03 121.0 0.83 -48.1- 38.6
Previous DOTS treatment 37 2.00 1.22 311 2.07 1.710 0.80 -0.64 - 0.5
Previous DOTS Plus treatment 36 .03 0.16 311 0.13 0.421 0.15 -0.24 - 0.04
Number of people living in the same house 37 2.73 1.75 311 3.21 1.82 0.13 -1.1 - 0.15
Number of children living in the same house 37 0.76 1.09 312 0.72 1.01 0.85 -0.31- 0.38
  Success Failure Total p–value  
Isoniazid Resistant (36) 100.0% (248) 92.5% 284 93.4% .41
Sensitive (0) 0% (15) 5.6% (15) 4.9%
Rifampin Resistant (25) 69.4% (214) 81.1% (239) 79.7% .19
Sensitive (11) 30.6% (48) 18.2% (59) 19.7%
Ethambutol Resistant (30) 83.3% (213) 80.4% (243) 80.7% .87
Sensitive (6) 16.7% (51) 19.2% (57) 18.9%
Pyrazinamide Resistant (3) 50.0% (70) 47.6% (73) 47.7% .97
Sensitive (3) 50.0% (76) 51.7% (79) 51.6%
Streptomycin Resistant (34) 94.4% (231) 88.5% (265) 89.2% .28
Sensitive (2) 5.6% (30) 11.5% (32) 10.8%
Previous TB treatment Yes (37) 100.0% (307) 98.1% (344) 98.3% .39
No (0) 0% (6) 1.9% (6) 1.7%
Marital status Married (21) 56.8% (155) 50.0% (176) 50.7% .50
Living Together (0) 0% (3) 1.0% (3) 0.9%
Single (14) 37.8% (111) 35.8% (125) 36.0%q
Divorced (0) 0% (24) 7.7% (24) 6.9%
Widowed (2) 5.4% (12) 3.9% (14) 4.0%
Separated (0) 0% (5) 1.6% (5) 1.4%
Employment status Employed (7) 18.9% (50) 16.0% (57) 16.3% .63
Pensioner (1) 2.7% (10) 3.2% (11) 3.2%
Student (0) 0% (8) 2.6% (8) 2.3%
Unemployed (29) 78.4% (226) 72.4% (255) 73.1%
Housework (0) 0% (14) 4.5% (14) 4.0%
Ever been in prison Yes (17) 45.9% (113) 36.2% (130) 37.2% .24
No (20) 54.1% (199) 63.8% (219) 62.8%
Injection drug user Yes (2) 5.7% (62) 19.9% (64)18.4% .04
No (33) 94.3% (250) 80.1% (283) 81.6%
Prostitution Yes (0) 0% (1) 0.3% (1) 0.3% .74
No (34) 100.0% (304) 99.7% (338) 99.7%
Homeless Yes (1) 2.8% (7) 2.3% (8) 2.3% .84
No (35) 97.2% (303) 97.7% (338) 97.7%
Health Worker Yes (0) 0% (3) 1.0% (3) 0.9% .55
No (36) 100.0% (307) 99.0% (343) 99.1%
Migrant worker Yes (1) 2.8% (11) 3.5% (12) 3.5% .81
No (35) 97.2% (299) 96.5% (334) 96.5%
Traveler (out of Armenia) Yes (2) 5.6% (35) 11.3% (37) 10.7% .29
No (34) 94.4% (275) 88.7% (309) 89.3%
Contact with MDR-TB case Yes (3) 8.3% (75) 24.3% (78) 22.6% .03
No (33) 91.7% (234) 75.7% (267) 77.4%
Tobacco use Yes (27) 73.0% (191) 61.4% (218) 62.6% .16
No (10) 27.0% (120) 38.6% (130) 37.4%
Alcohol use Yes (27) 73.0% (170) 54.5% (197) 56.4% .03
No (10) 27.0% (142) 45.5% (152) 43.6%
n: Sample size, SD: Standard deviation, CI: Confidence interval
Table 4: Association between treatment successes to failure.
Variables OR (95% CI) P - value
Treatment duration 1.1 (1.03 - 1.18) 0.003
Days to end hospitalization phase 1.0 (0.99 - 1.01) 0.26
Previous Contact with MDR-TB 0.32 (0.07 - 1.49) 0.15
Alcohol Severity    
Moderate 3.5 (1.34 - 9.15) 0.01
Excessive 6.26x10-9 (0.0 - ∞) 0.99
Injection drug users 0.66(0.006 - 0.7) 0.02
OR: Odds Ratio, CI: Confidence interval
Table 5: Final multivariate model.
Discussion
MDR TB treatment is a challenge as there are limited treatment options. MDR-TB treatment is left with fewer treatment options due to the emergence of resistant strains. To cure an MDR-TB patient, it takes 18 - 24 months with second-line drugs (SLDs) as reported in Global tuberculosis 2014 report [1]. Second line drugs are less efficacious, more toxic, less tolerated and considerably more expensive [1,7,8] which could result in more serious adverse effects, treatment defaults, extending the treatment duration. Our study showed longer the treatment duration better the treatment outcome, which was consistent with study done by Ahuja., et al. [4] and global tuberculosis 2014 report [1]. Our patient received empiric treatment initially and then tailored based on drug sensitivity testing and adverse effects to achieve success resulting in lengthy treatment.
Literature showed alcohol and illicit drug use to be the important risk factors for contracting the disease and poor treatment outcome and also they have been implicated as the cause of TB epidemics in many countries. Few studies suggested that low to moderate alcohol intake is not associated with increased risk of TB disease [15]. However, there seem to be a substantial risk increase among people who drink more than 40g alcohol per day, and or have an alcohol use disorder. This was clearly demonstrated by many studies and systematic reviews [7,14,15,23]. The role of heavy alcohol consumption and illicit drug use as a risk factor for contracting tuberculosis can be explained by specific social mixing patterns in settings such as bars, shelters for homeless, prisons, and social institutions as well as by direct toxicity to the immune system [5]. The effects of alcohol and drug use on the immune system include impairment of cell mediated immunity and macrophage function that reduce the ability to clear the infection and result in less favorable outcome [5,24,25]. Our data showed correlation between moderate alcohol use with treatment success and excessive alcohol use showed trend towards treatment failure. This trend was probably secondary to very low number of patients with excess alcohol use (35, 10%) compared to moderate alcohol use 162 (46.4). Many studies have demonstrated the beneficial effects of moderate alcohol use in lowering myocardial infarction, heart failure and ischemic stroke rates and reduced risk of dementia, diabetes and osteoporosis [26-28], however there were no studies looking at treatment success of TB or MDR-TB with moderate alcohol use. Our data showed correlation between injection drug use with treatment failure and is consistent with studies done by Bendayan., et al. [7] and Deiss., et al. [29].
Key to prevent the spread and achieve the cure of MDR-TB and XDR-TB is implementation of proven strategies to control alcoholism and intravenous drug use. Some of the proven strategies are: 1. a. Limiting alcohol consumption by increasing the taxes [30,31,] b. Imposing limits on days of sale for off-premises settings (e.g., grocery, convenience or liquor stores) [32,33] c. Regulation of Alcohol Outlet Density [34]. 2. Screening individuals for excessive drinking, drug use and delivering a brief intervention, which provides personalized feedback about the risks and consequences of excessive drinking and drug use [35]. 3. Raising awareness through community activities and participation [35]. 4. Political commitment in implementing strict policies in controlling alcohol and drug use at national and municipal level [35].
Limitations
This study has several limitations like small sample size, limited to a region, only the patients with MDR-TB & XDR-TB who could tolerate the treatment and willing to complete the treatment were included in the study. Individualized treatment was given based on patient profile instead of randomization of treatment, there were no consistent follow-ups and some have left without treatment completion. HIV disease is an important risk factor for acquiring the disease and achieving cure of either susceptible or resistant tuberculosis or their status on HIV is unknown. Finally there was large amount of patients with unknown treatment status who were included in failure group resulting lower percentage of cure.
This study highlights the need for randomized studies with large sample size evaluating the individualized treatment regimens, moderate alcohol consumption and TB or MDR-TB treatment outcomes and urgent need for more efficacious, well tolerated, drug regimens to cure MDR-TB.
Conclusion
Analysis of data showed that, longer the treatment duration and moderate alcohol use (a daily intake of any kind of alcohol beverage less than 3 glasses or 40 grams), better the treatment outcome and higher the injection drug use, lower the success. Excessive alcohol use (a daily intake of any kind of alcohol beverage more than 3 glasses), showed trend towards negative correlation with success, suggesting excessive alcohol use had poor treatment outcome.
The key for success in prevention and cure of MDR-TB and XDR-TB is implementation of public health strategies to control alcoholism and intravenous drug use.
Acknowledgements
My sincere thanks to my mentors Dr. Stephanie Factor and Dr. Keith Sigel for providing me the data and guiding me to write the manuscript and Dr. Godbold James, who helped me with SPSS statistics.
Grants: None
Conflict of Interest: None
Bibliography
  1. World Health Organization. “Global tuberculosis report 2014”. Switzerland, Geneva. (2014).
  2. Sharma SK and Mohan A. “Multidrug-resistant tuberculosis: a menace that threatens to destabilize tuberculosis control”. Chest 130.1 (2006): 261-272.
  3. World Health Organization. “Guidelines for the programmatic management of drug resistant tuberculosis”. Switzerland, Geneva (2008).
  4. Ahuja SD., et al. “Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients”. PLoS Medicine 9.8 (2012): e1001300.
  5. Johnston JC., et al. “Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis”. PLoS One 4.9 (2009): e6914.
  6. Orenstein EW., et al. “Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis”. Lancet Infectious Disease 9.3 (2009): 153-161.
  7. Bendayan D., et al. “Outcome of hospitalized MDR-TB patients: Israel 2000-2005”. European Journal of Clinical Microbiology Infectious Disease 30.3 (2011): 375-379.
  8. Laserson KF., et al. “Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis”. International Journal of Tuberculosis and Lung Disease 9.6 (2005): 640-645.
  9. Kliiman K and Altraja A. “Predictors of poor treatment outcome in multi- and extensively drug-resistant pulmonary TB”. European respiratory journal 33.5 (2009): 1085-1094.
  10. Gandhi NR., et al. “Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa”. Lancet 368.9547 (2006): 1575-1580.
  11. World Health Organization. “Anti-tuberculosis drug resistance in the world report 2008”. Switzerland, Geneva. (2008).
  12. Caminero JA. “Multidrug-resistant tuberculosis: epidemiology, risk factors and case finding”. International Journal of Tuberculosis and Lung Disease 14.4 (2010): 382-390.
  13. Caminero JA. “Extensively drug-resistant tuberculosis: is its definition correct?”. European Respiratory Journal 32.5 (2008): 1413-1415.
  14. Kiwuwa MS., et al. “Patient and health service delay in pulmonary tuberculosis patients attending a referral hospital: a cross-sectional study”. BMC Public Health 5 (2005): 122.
  15. Lonnroth K., et al. “Alcohol use as a risk factor for tuberculosis - a systematic review”. BMC Public Health 8 (2008): 289.
  16. Mishra P., et al. “Adherence is associated with the quality of professional-patient interaction in Directly Observed Treatment Short-course, DOTS”. Patient Education and Counseling 63.1-2 (2006): 29-37.
  17. Jakubowiak WM., et al. “Risk factors associated with default among new pulmonary TB patients and social support in six Russian regions”. International Journal of Tuberculosis and Lung Disease 11.1 (2007): 46-53.
  18. Holtz TH., et al. “Risk factors associated with default from multidrug-resistant tuberculosis treatment, South Africa, 1999-2001”. International Journal of Tuberculosis and Lung Disease 10.6 (2006): 649-655.
  19. Cox HS., et al. “Emergence of extensive drug resistance during treatment for multidrug-resistant tuberculosis”. New England Journal of Medicine 359.22 (2008): 2398-2400.
  20. Kurbatova EV., et al. “Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects”. Tuberculosis 92.5 (2012): 397-403.
  21. Falzon D., et al. “Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes” European Respiratory Journal 42.1 (2013): 156-168.
  22. Mishra P., et al. “Adherence is associated with the quality of professional-patient interaction in Directly Observed Treatment Short-course, DOTS”. Patient Education and Counseling 63.1-2 (2006): 29-37.
  23. Rehm J., et al. “The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review”. BMC Public Health 9 (2009): 450.
  24. Friedman H., et al. “Microbial infections, immunomodulation, and drugs of abuse”. Clinical Microbiology Reviews 16.2 (2003): 209-219.
  25. Wei G., et al. “Opioid-induced immunosuppression: is it centrally mediated or peripherally mediated?”. Biochemical Pharmacology 65.11 (2003): 1761-1766.
  26. Baum-Baicker C. “The health benefits of moderate alcohol consumption: a review of the literature”. Drug and Alcohol Dependence 15.3 (1985): 207-227.
  27. Standridge JB., et al. “Alcohol consumption: an overview of benefits and risks”. The Southern Medical Journal 97.7 (2004): 664-672.
  28. Thakker KD. “An overview of health risks and benefits of alcohol consumption”. Alcoholism: Clinical and Experimental Research 22.7S (1998): 285S-298S.
  29. Deiss RG., et al. “Tuberculosis and illicit drug use: review and update”. Clinical Infectious Diseases 48.1 (2009): 72-82.
  30. Elder RW., et al. “The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms”. American Journal of Preventive Medicine 38.2 (2010): 217-229.
  31. Task Force on Community Preventive Service. “Increasing alcoholic beverage taxes is recommended to reduce excessive alcohol consumption and related harms”. American Journal of Preventive Medicine 38.2 (2010): 230-232.
  32. Middleton JC., et al. “Effectiveness of policies maintaining or restricting days of alcohol sales on excessive alcohol consumption and related harms”. American Journal of Preventive Medicine 39.6 (2010): 575-589.
  33. Task Force on Community Preventive Service. “Recommendations on maintaining limits on days and hours of sale of alcoholic beverages to prevent excessive alcohol consumption and related harms”. American Journal of Preventive Medicine39.6 (2010): 605-606.
  34. Campbell CA., et al. “The effectiveness of limiting alcohol outlet density as a means of reducing excessive alcohol consumption and alcohol-related harms”. American Journal of Preventive Medicine 37.6 (2009): 556-569.
  35. World Health Organization. “Strategies to reduce the harmful use of alcohol”. Switzerland, Geneva. (2008).
Copyright: © 2016 Vinod Namana and Pankaj Mathur. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events

December Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the November issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before December 19, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.