Science.gov

Sample records for smear-positive tuberculosis treatment

  1. Treatment outcome of new smear positive pulmonary tuberculosis patients in Penang, Malaysia

    PubMed Central

    2014-01-01

    Background According to the World Health Organization’s recent report, in Malaysia, tuberculosis (TB) treatment success rate for new smear positive pulmonary tuberculosis (PTB) patients is still below the global success target of 85%. In this study, we evaluated TB treatment outcome among new smear positive PTB patients, and identified the predictors of unsuccessful treatment outcome and longer duration of treatment (i.e., > 6 months). Methods The population in this study consisted of all new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. During the study period, a standardized data collection form was used to obtain socio-demographic, clinical and treatment related data of the patients from their medical charts and TB notification forms (Tuberculosis Information System; TBIS). These data sources were reviewed at the time of the diagnosis of the patients and then at the subsequent follow-up visits until their final treatment outcomes were available. The treatment outcomes of the patients were reported in line with six outcome categories recommended by World Health Organization. Multiple logistic regression analysis was used to find the independent risk factors for unsuccessful treatment outcome and longer treatment duration. Data were analyzed using the PASW (Predictive Analysis SoftWare, version 19.0. Armonk, NY: IBM Corp). Results Among the 336 PTB patients (236 male and 100 female) notified during the study period, the treatment success rate was 67.26% (n = 226). Out of 110 patients in unsuccessful outcome category, 30 defaulted from the treatment, 59 died and 21 were transferred to other health care facilities. The mean duration of TB treatment was 8.19 (SD 1.65) months. In multiple logistic regression analysis, risk factors for unsuccessful treatment outcome were foreign nationality, male gender and being illiterate. Similarly, risk factors for mortality due to TB

  2. Clinical significance of smear positivity for acid-fast bacilli after ≥5 months of treatment in patients with drug-susceptible pulmonary tuberculosis

    PubMed Central

    Kang, Hyung Koo; Jeong, Byeong-Ho; Lee, Hyun; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Koh, Won-Jung

    2016-01-01

    Abstract Patients with pulmonary tuberculosis (TB) with acid-fast bacilli (AFB)-positive sputum smear at 5 months or later during treatment are considered to be cases of treatment failure according to World Health Organization guidelines. This study evaluated the proportion, clinical characteristics, and significance of positive sputum smears after ≥5 months of standard treatment in patients with drug-susceptible pulmonary TB. This was a retrospective cohort study of 1611 patients with culture-confirmed drug-susceptible pulmonary TB who received standard anti-TB treatment from January 2009 to February 2014. Forty-one patients (2.5%) who were smear-positive after ≥5 months of treatment and 123 age- and sex-matched control patients were evaluated. Among the 41 smear-positive patients, culture of the sputum specimens yielded Mycobacterium tuberculosis (MTB) in 1 patient (2.4%), nontuberculous mycobacteria (NTM) in 7 (17.1%), and no growth in the remaining 33 patients (80.5%). Treatment was successfully completed in 40 patients (97.6%) with prolongation of the continuation phase regimens without change to second-line anti-TB treatment. In patients with smear positivity after ≥5 months of treatment compared with controls, cavitation on chest radiographs (53.7% vs. 25.2%, P = 0.001), bilateral involvement (51.2% vs. 30.1%, P = 0.01) and combined pleural effusion (26.8% vs. 10.6%, P = 0.01) were found more frequently at the time of treatment initiation, and paradoxical response occurred more commonly (19.5% vs. 3.3%, P = 0.002) during treatment. Smear-positive sputum after ≥5 months of standard anti-TB treatment was mainly because of nonviable MTB bacilli or NTM in patients with drug-susceptible pulmonary TB. AFB smear alone should not be used to assess treatment failure and careful examination of microbiologic status, including culture and drug susceptibility testing, is needed before making changes to retreatment regimens or empirical second

  3. Clinical significance of smear positivity for acid-fast bacilli after ≥5 months of treatment in patients with drug-susceptible pulmonary tuberculosis.

    PubMed

    Kang, Hyung Koo; Jeong, Byeong-Ho; Lee, Hyun; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Koh, Won-Jung

    2016-08-01

    Patients with pulmonary tuberculosis (TB) with acid-fast bacilli (AFB)-positive sputum smear at 5 months or later during treatment are considered to be cases of treatment failure according to World Health Organization guidelines. This study evaluated the proportion, clinical characteristics, and significance of positive sputum smears after ≥5 months of standard treatment in patients with drug-susceptible pulmonary TB.This was a retrospective cohort study of 1611 patients with culture-confirmed drug-susceptible pulmonary TB who received standard anti-TB treatment from January 2009 to February 2014. Forty-one patients (2.5%) who were smear-positive after ≥5 months of treatment and 123 age- and sex-matched control patients were evaluated.Among the 41 smear-positive patients, culture of the sputum specimens yielded Mycobacterium tuberculosis (MTB) in 1 patient (2.4%), nontuberculous mycobacteria (NTM) in 7 (17.1%), and no growth in the remaining 33 patients (80.5%). Treatment was successfully completed in 40 patients (97.6%) with prolongation of the continuation phase regimens without change to second-line anti-TB treatment. In patients with smear positivity after ≥5 months of treatment compared with controls, cavitation on chest radiographs (53.7% vs. 25.2%, P = 0.001), bilateral involvement (51.2% vs. 30.1%, P = 0.01) and combined pleural effusion (26.8% vs. 10.6%, P = 0.01) were found more frequently at the time of treatment initiation, and paradoxical response occurred more commonly (19.5% vs. 3.3%, P = 0.002) during treatment.Smear-positive sputum after ≥5 months of standard anti-TB treatment was mainly because of nonviable MTB bacilli or NTM in patients with drug-susceptible pulmonary TB. AFB smear alone should not be used to assess treatment failure and careful examination of microbiologic status, including culture and drug susceptibility testing, is needed before making changes to retreatment regimens or empirical second-line anti

  4. Impact of changing diagnostic criteria for smear-positive tuberculosis: a cohort study in Malawi.

    PubMed

    Koole, O; Munthali, L; Mhango, B; Mpunga, J; Glynn, J R; Crampin, A C

    2014-07-01

    We assessed the impact on measured burden and outcomes of the revised World Health Organization and Malawi guidelines reclassifying people with single (including 'scanty') positive smears as smear-positive pulmonary tuberculosis cases. In a retrospective cohort in rural Malawi, 567 (34%) of 1670 smear-positive episodes were based on single positive smears (including 176 with scanty smears). Mortality rates and the proportion starting treatment were similar in those with two positive smears or single, non-scanty smears. Those with single scanty smears had higher mortality and a lower proportion starting treatment. The reclassification will increase the reported burden substantially, but should improve treatment access.

  5. Predicting the Incidence of Smear Positive Tuberculosis Cases in Iran Using Time Series Analysis

    PubMed Central

    MOOSAZADEH, Mahmood; KHANJANI, Narges; NASEHI, Mahshid; BAHRAMPOUR, Abbas

    2015-01-01

    Background: Determining the temporal variation and forecasting the incidence of smear positive tuberculosis (TB) can play an important role in promoting the TB control program. Its results may be used as a decision-supportive tool for planning and allocating resources. The present study forecasts the incidence of smear positive TB in Iran. Methods: This a longitudinal study using monthly tuberculosis incidence data recorded in the Iranian National Tuberculosis Control Program. The sum of registered cases in each month created 84 time points. Time series methods were used for analysis. Based on the residual chart of ACF, PACF, Ljung-Box tests and the lowest levels of AIC and BIC, the most suitable model was selected. Results: From April 2005 until March 2012, 34012 smear positive TB cases were recorded. The mean of TB monthly incidence was 404.9 (SD=54.7). The highest number of cases was registered in May and the difference in monthly incidence of smear positive TB was significant (P<0.001). SARIMA (0,1,1)(0,1,1)12 was selected as the most adequate model for prediction. It was predicted that the incidence of smear positive TB for 2015 will be about 9.8 per 100,000 people. Conclusion: Based on the seasonal pattern of smear positive TB recorded cases, seasonal ARIMA model was suitable for predicting its incidence. Meanwhile, prediction results show an increasing trend of smear positive TB cases in Iran. PMID:26744711

  6. True status of smear-positive pulmonary tuberculosis defaulters in Malawi.

    PubMed Central

    Kruyt, M. L.; Kruyt, N. D.; Boeree, M. J.; Harries, A. D.; Salaniponi, F. M.; van Noord, P. A.

    1999-01-01

    The article reports the results of a study to determine the true outcome of 8 months of treatment received by smear-positive pulmonary tuberculosis (PTB) patients who had been registered as defaulters in the Queen Elizabeth Central Hospital (QECH) and Mlambe Mission Hospital (MMH), Blantyre, Malawi. The treatment outcomes were documented from the tuberculosis registers of all patients registered between 1 October 1994 and 30 September 1995. The true treatment outcome for patients who had been registered as defaulters was determined by making personal inquiries at the treatment units and the residences of patients or relatives and, in a few cases, by writing to the appropriate postal address. Interviews were carried out with patients who had defaulted and were still alive and with matched, fully compliant PTB patients who had successfully completed the treatment to determine the factors associated with defaulter status. Of the 1099 patients, 126 (11.5%) had been registered as defaulters, and the true treatment outcome was determined for 101 (80%) of the latter; only 22 were true defaulters, 31 had completed the treatment, 31 had died during the treatment period, and 17 had left the area. A total of 8 of the 22 true defaulters were still alive and were compared with the compliant patients. Two significant characteristics were associated with the defaulters; they were unmarried; and they did not know the correct duration of antituberculosis treatment. Many of the smear-positive tuberculosis patients who had been registered as defaulters in the Blantyre district were found to have different treatment outcomes, without defaulting. The quality of reporting in the health facilities must therefore be improved in order to exclude individuals who are not true defaulters. PMID:10361755

  7. True status of smear-positive pulmonary tuberculosis defaulters in Malawi.

    PubMed

    Kruyt, M L; Kruyt, N D; Boeree, M J; Harries, A D; Salaniponi, F M; van Noord, P A

    1999-01-01

    The article reports the results of a study to determine the true outcome of 8 months of treatment received by smear-positive pulmonary tuberculosis (PTB) patients who had been registered as defaulters in the Queen Elizabeth Central Hospital (QECH) and Mlambe Mission Hospital (MMH), Blantyre, Malawi. The treatment outcomes were documented from the tuberculosis registers of all patients registered between 1 October 1994 and 30 September 1995. The true treatment outcome for patients who had been registered as defaulters was determined by making personal inquiries at the treatment units and the residences of patients or relatives and, in a few cases, by writing to the appropriate postal address. Interviews were carried out with patients who had defaulted and were still alive and with matched, fully compliant PTB patients who had successfully completed the treatment to determine the factors associated with defaulter status. Of the 1099 patients, 126 (11.5%) had been registered as defaulters, and the true treatment outcome was determined for 101 (80%) of the latter; only 22 were true defaulters, 31 had completed the treatment, 31 had died during the treatment period, and 17 had left the area. A total of 8 of the 22 true defaulters were still alive and were compared with the compliant patients. Two significant characteristics were associated with the defaulters; they were unmarried; and they did not know the correct duration of antituberculosis treatment. Many of the smear-positive tuberculosis patients who had been registered as defaulters in the Blantyre district were found to have different treatment outcomes, without defaulting. The quality of reporting in the health facilities must therefore be improved in order to exclude individuals who are not true defaulters.

  8. Determinants of consultation, diagnosis and treatment delays among new smear-positive pulmonary tuberculosis patients in Morocco: a cross-sectional study.

    PubMed

    Akrim, M; Bennani, K; Essolbi, A; Sghiar, M; Likos, A; Benmamoun, A; Menzhi, O El; Maaroufi, A

    2014-12-17

    We conducted a cross-sectional survey in 2012 in 12 selected provinces and prefectures in Morocco to determine consultation delay (patient delay), diagnosis delay and treatment delay (health system delays), and factors relating to these delays. The sample included 250 eligible and consenting newly diagnosed smearpositive pulmonary tuberculosis patients who were interviewed at the time of their registration within Diagnosis of Tuberculosis and Respiratory Diseases Reference Centers (CDTMR) or Integrated Health Centers (CSI) using a pretested and structured questionnaire. The median total delay was 46 days [inter-quartile interval (IQI) = 29-84 days]. Patient delay (median = 20; IQI = 8-47 days) was higher than health system delay (median=15; IIQ = 7-35 days). Being illiterate, thinking symptoms will disappear by themselves; having financial constraints and feeling fear of diagnosis or social isolation were associated with patient delay. Consulting first in the private sector or having 3 or more consultations before diagnosis was associated with health system delay.

  9. Adverse Events in Treating Smear-Positive Tuberculosis Patients in China.

    PubMed

    Zhang, Tao; Du, Jian; Yin, Xiaoyan; Xue, Fuzhong; Liu, Yanxun; Li, Runzi; Luo, Cheng; Li, Liang; Li, Xiujun

    2016-01-01

    This study aimed to estimate the adverse events (AE) rate during anti-tuberculosis treatment and to explore AE-related risk factors. New and previously treated smear-positive tuberculosis (TB) cases were enrolled from eight regions in China between April 2009 and October 2010. The AE rate was estimated, and AE risk factors during anti-TB treatment were assessed using Cox proportional models. Among 2091 Chinese subjects with anti-TB treatment, 462 (22.1%, 95% confidence interval (CI), 20.3-23.9) patients developed AE, with liver injury and gastrointestinal reactions constituting the most common AE. Specifically, 9.8% (95% CI, 8.5-11.1) and 6.3% (95% CI, 5.3-7.4) developed liver injuries and gastrointestinal reactions, respectively. We found that AE rate differed by regions, TB knowledge score, symptoms score and smoking status. Liver injuries were associated with age, sex and smoking status; gastrointestinal reactions were associated with education level and symptom score. Improving patients' knowledge on TB could reduce AE rate.

  10. Prevalence of smear-positive pulmonary tuberculosis among prisoners in Malawi: a national survey.

    PubMed

    Banda, H T; Gausi, F; Harries, A D; Salaniponi, F M

    2009-12-01

    A cross-sectional cell-to-cell survey was conducted in 18 of 22 prisons in Malawi to determine the period prevalence of smear-positive pulmonary tuberculosis (PTB). In each prison, prisoners were interviewed using a structured questionnaire. Prisoners with cough of >1 week's duration were investigated by sputum smear examination. Of 7661 prisoners, 3887 had cough of > or =1 week, of whom 3794 submitted three sputum specimens: 54 (0.7%) had smear-positive PTB. The prevalence of PTB was higher in large urban prisons (1.1%) than in district prisons (0.3%, P < 0.001). More needs to be done to improve TB control in urban prisons.

  11. Spatio-Temporal Analysis of Smear-Positive Tuberculosis in the Sidama Zone, Southern Ethiopia

    PubMed Central

    Dangisso, Mesay Hailu; Datiko, Daniel Gemechu; Lindtjørn, Bernt

    2015-01-01

    Background Tuberculosis (TB) is a disease of public health concern, with a varying distribution across settings depending on socio-economic status, HIV burden, availability and performance of the health system. Ethiopia is a country with a high burden of TB, with regional variations in TB case notification rates (CNRs). However, TB program reports are often compiled and reported at higher administrative units that do not show the burden at lower units, so there is limited information about the spatial distribution of the disease. We therefore aim to assess the spatial distribution and presence of the spatio-temporal clustering of the disease in different geographic settings over 10 years in the Sidama Zone in southern Ethiopia. Methods A retrospective space–time and spatial analysis were carried out at the kebele level (the lowest administrative unit within a district) to identify spatial and space-time clusters of smear-positive pulmonary TB (PTB). Scan statistics, Global Moran’s I, and Getis and Ordi (Gi*) statistics were all used to help analyze the spatial distribution and clusters of the disease across settings. Results A total of 22,545 smear-positive PTB cases notified over 10 years were used for spatial analysis. In a purely spatial analysis, we identified the most likely cluster of smear-positive PTB in 192 kebeles in eight districts (RR= 2, p<0.001), with 12,155 observed and 8,668 expected cases. The Gi* statistic also identified the clusters in the same areas, and the spatial clusters showed stability in most areas in each year during the study period. The space-time analysis also detected the most likely cluster in 193 kebeles in the same eight districts (RR= 1.92, p<0.001), with 7,584 observed and 4,738 expected cases in 2003-2012. Conclusion The study found variations in CNRs and significant spatio-temporal clusters of smear-positive PTB in the Sidama Zone. The findings can be used to guide TB control programs to devise effective TB control

  12. LED fluorescence microscopy increases the detection of smear-positive pulmonary tuberculosis in medical colleges of India.

    PubMed

    Reza, L W; Satyanarayana, S; Pandey, A; Kumar, S; Devendrappa, N M; Anand, L; Singh, G; Kumar, A M V; Chadha, S S; Wilson, N; Sachdeva, K S; Nair, S A

    2013-09-21

    In July 2012, light-emitting diode fluorescence microscopy (LED-FM) replaced conventional light microscopy using Ziehl-Neelsen stain in the detection of sputum-positive pulmonary tuberculosis in 190 microscopy centres of medical colleges operating under India's Revised National Tuberculosis Control Programme. We compared the performance of LED-FM (July-December 2012) to that of conventional microscopy (July-December 2011) across 190 sites. Of 222 658 patients examined using conventional microscopy, 28 042 (12.6%) were smear-positive, while of 224 714 examined using LED-FM, 33 552 (14.9%) were smear-positive, an additional yield of 5251 cases after adjusting for the increase in patients examined. We recommend replacing conventional microscopy with LED-FM in high workload microscopy centres in India.

  13. Impact of Educational Intervention on Patients Behavior with Smear-positive Pulmonary Tuberculosis: A Study Using the Health Belief Model

    PubMed Central

    Jadgal, Khair Mohammad; Nakhaei-Moghadam, Tayebeh; Alizadeh-Seiouki, Hadi; Zareban, Iraj; Sharifi-Rad, Javad

    2015-01-01

    Introduction: Tuberculosis is a single-agent infectious disease, which is the major cause of death around the world. Approximately one third of the world’s population is infected with tuberculosis (TB) bacilli and at risk of developing active TB. The purpose of this study was determined the impact of education based on health belief model in promoting behavior of smear-positive pulmonary TB among patients in Chabahar city, Iran. Material and methods: Of the 80 smear-positive pulmonary TB who referred to health centers in Chabahar voluntarily participated in this interventional study. The data collected using questionnaire based on health belief model. The data were analyzed by using paired t-test, independent t-test, pearson correlation and chi-square test with SPSS 16. Results: The cognitive skills were increased significantly from 6.10 to 6.88 after intervention. All behavioral skills were increased significantly from 2.08 to 2.88 after implementing the intervention. Perceived severity was increased from11.08to12.19 significantly. Percepted benefits were enhanced significantly from 11.48 to 12.23. Mean percepted barrier was decreased significantly from 17.52 to 16.68. Conclusion: Findings demonstrated that implementing educational intervention programs can increase the level of knowledge and behavior of patients regarding smear- positive pulmonary TB initiatives. PMID:26543411

  14. Primary Multidrug Resistant Tuberculosis and Utility of Line Probe Assay for Its Detection in Smear-Positive Sputum Samples in a Tertiary Care Hospital in South India

    PubMed Central

    Yacoob, Fahmiya Leena; Philomina Jose, Beena; Karunakaran Lelitha, Sarada Devi; Sreenivasan, Sreelatha

    2016-01-01

    In a high tuberculosis burdened country like India, rapid, cost-effective, and reliable diagnostic tools for tuberculosis are an urgent need of the hour to prevent inappropriate treatment strategies and further spread of resistance. This study aimed to estimate the proportion of new smear-positive tuberculosis cases with primary resistance to rifampicin and/or isoniazid as well as identify the common mutations associated with it. Sputum of 200 newly diagnosed smear-positive cases of 1+ score and above was directly subjected to Line Probe Assay using the GenoType MTBDRplus assay kit. All samples were inoculated onto solid media and 61 samples were inoculated in automated liquid culture also. The Line Probe Assay gave hundred percent interpretable results with 2.5% of the study population showing resistant pattern. Only 1% of the cases were primary multidrug resistant tuberculosis and 1.5% showed isoniazid monoresistance. S531L and C15T were the most common genetic mutations seen for rifampicin and isoniazid resistance, respectively. 40% had absent rpoB wild type 8 band indicating probable silent mutation after clinical correlation. The average turnaround time for Line Probe Assay was far less (3.8 days) as compared to solid and liquid cultures (35.6 days and 13.5 days, resp.). PMID:27099794

  15. Cost-effectiveness of chemotherapy for sputum smear-positive pulmonary tuberculosis in Malawi, Mozambique and Tanzania.

    PubMed

    de Jonghe, E; Murray, C J; Chum, H J; Nyangulu, D S; Salomao, A; Styblo, K

    1994-01-01

    The cost-effectiveness of chemotherapy for pulmonary sputum smear-positive tuberculosis was examined in the national tuberculosis control programmes of Malawi, Mozambique and Tanzania. In these three programmes, routine cure rates have exceeded 80 per cent. Average, average incremental and marginal unit costs for standard, short-course and retreatment regimens with and without hospitalization have been measured. The average incremental cost per year of life saved through chemotherapy ranged from US $0.90-3.10. In all conditions, short-course chemotherapy is preferable to standard 12-month chemotherapy. When hospitalization during the intensive phase of chemotherapy increases the cure rate by 10-15 percentage points, it can be relatively cost-effective. Analysing the cost-effectiveness of short-course and standard chemotherapy, where the depth of the margin of benefit is different, illustrates some of the dangers of simplistic use of cost-effectiveness ratios.

  16. Did FIDELIS projects contribute to the detection of new smear-positive pulmonary tuberculosis cases in China?

    PubMed Central

    Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.

    2016-01-01

    Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low. PMID:27695680

  17. Did FIDELIS projects contribute to the detection of new smear-positive pulmonary tuberculosis cases in China?

    PubMed Central

    Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.

    2016-01-01

    Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low.

  18. Trend of Smear-positive Pulmonary Tuberculosis in Iran during 1995–2012: A Segmented Regression Model

    PubMed Central

    Khazaei, Salman; Soheilyzad, Mokhtar; Molaeipoor, Leila; Khazaei, Zaher; Rezaeian, Shahab; Khazaei, Somayeh

    2016-01-01

    Background: Describing trend in tuberculosis (TB) over time can play an important role to assess the disease control strategies and predict the future morbidity and mortality. This study aimed to determine the incidence trend of smear-positive pulmonary tuberculosis (SPPT) in sub-age and sex groups during the years of 1995–2012. Methods: This retrospective cohort study was performed in 2015 by using the dataset regarding National Statistics of SPPT reported by World Health Organization during 1995–2012. Annual percent changes (APCs) and average annual percent changes (AAPCs) were estimated to determine the summery statistics of trend using segmented regression model. Results: During 1995–2012, there were 96,579 SPPT case notifications in Iran (male to female ratio: 0.99). There was only one change point in 1997 for SPPT incidence in subgroups of age and sex during 1995–2012. The AAPCs for both genders and also all three age groups had a significant descending trend during the time period (P < 0.05). Conclusions: Our results showed a downward trend in the SPPT incidence. It seems that to achieve the set goals and high successful in TB control program especially reduction in SPPT, pay more attention to old age and males should be considered. In addition, improvement of clinical and medical care services and notification processes would be imperative. PMID:27413517

  19. Frequency of Latent and Smear Positive Tuberculosis in Chronic Psychotic Disorders

    PubMed Central

    Ebrahimi, Hannan; Mohammadi, Alieh; Jahromi, Sina Khajeh; Naghdipour, Misa; Ebrahimi, Hossein

    2013-01-01

    Objective Screening is one of the ways to combat Tuberculosis (TB) and should be mostly concentrated on groups showing some symptoms of the disease. Tuberculosis can be transferred from person to person in laboratories, prisons and psychiatry hospitals. The purpose of this study was to survey pulmonary TB in patients with schizophrenia in Rasht. Methods In this descriptive-cross sectional, Two hundred fifty seven consecutive patients with chronic psychotic disorder hospitalized in psychotic hospitals underwent purified protein derivative (PPD) test. PPD test was done with the unit 5T which was injected subcutaneously on anterior surface and at the top of left forearm. The results of the test were interpreted by the pen technique method and based on transverse diameter of induration of about 48-72 hrs. Induration size due to hypersensitivity to PPD more than 10mm was considered positive. Patients with positive PPD test underwent complementary sputum smear. Data were analyzed using chi- square and T test. Results The mean age of patients was 45±10 years; 75.5% were male, 74.7% were single, 10.5% married, 7.8% divorced, and 68.1% were smokers. These patients suffered from chronic psychotic disorder at the mean time of 15±7.9 years. In 74 patients (28%) positive PPD test were recorded, but active pulmonary TB was not found in complementary experiments of PPD sample. Based on data analysis, only age and gender showed a significant relationship with the results of the PPD test (P < 0.05). Conclusions This study showed that patients with positive PPD test are much more than the normal population, but active pulmonary TB was not observed in our samples. Since these patients are in clinical and closed places, more programs for screening are required. PMID:23682252

  20. Rate of recovery of Mycobacterium tuberculosis from frozen acid-fast-bacillus smear-positive sputum samples subjected to long-term storage in Northwest Ethiopia.

    PubMed

    Tessema, Belay; Beer, Joerg; Emmrich, Frank; Sack, Ulrich; Rodloff, Arne C

    2011-07-01

    Tuberculosis is a major public health problem in Ethiopia. The diagnosis and treatment of drug-resistant tuberculosis remain a challenge in the country. This study aimed to assess whether single morning sputum samples could be stored at -20 °C for extended periods of time at remote settings and then transported and successfully cultured for Mycobacterium tuberculosis. Single morning sputum samples were collected from all smear-positive tuberculosis patients diagnosed at Gondar Hospital, Gondar Health Center, Metemma Hospital, Bahir Dar Hospital, and Debre Markos Hospital in Northwest Ethiopia between March and July 2009. Specimens were stored at the study sites and sent to the mycobacteriology laboratory at the University Hospital, Leipzig, Germany, where specimens were processed and inoculated into the BacT/Alert 3D system and Lowenstein-Jensen and Gottsacker media. Ice packs were added in the package of the specimens during transport. A total of 319 patients were enrolled in this study. The median specimen storage time was 132 days (range, 16 to 180 days). Of all specimens, 283 (88.7%) were culture positive by any of the three culturing systems. M. tuberculosis isolates from four contaminated specimens in all culturing systems were successfully isolated on Middlebrook 7H10 agar; thereby, the recovery rate increased to 287 (90.0%). The length of time of sputum storage had no significant effect on the rate of recovery of M. tuberculosis in all culturing systems. In conclusion, single morning sputum specimens collected at remote settings stored at -20 °C for long periods of time without the addition of preservatives can yield a high recovery rate. These findings suggest a simple and cost-effective alternative method of sputum storage for epidemiological and drug resistance studies in low-resource countries. PMID:21562105

  1. Rate of Recovery of Mycobacterium tuberculosis from Frozen Acid-Fast-Bacillus Smear-Positive Sputum Samples Subjected to Long-Term Storage in Northwest Ethiopia ▿

    PubMed Central

    Tessema, Belay; Beer, Joerg; Emmrich, Frank; Sack, Ulrich; Rodloff, Arne C.

    2011-01-01

    Tuberculosis is a major public health problem in Ethiopia. The diagnosis and treatment of drug-resistant tuberculosis remain a challenge in the country. This study aimed to assess whether single morning sputum samples could be stored at −20°C for extended periods of time at remote settings and then transported and successfully cultured for Mycobacterium tuberculosis. Single morning sputum samples were collected from all smear-positive tuberculosis patients diagnosed at Gondar Hospital, Gondar Health Center, Metemma Hospital, Bahir Dar Hospital, and Debre Markos Hospital in Northwest Ethiopia between March and July 2009. Specimens were stored at the study sites and sent to the mycobacteriology laboratory at the University Hospital, Leipzig, Germany, where specimens were processed and inoculated into the BacT/Alert 3D system and Lowenstein-Jensen and Gottsacker media. Ice packs were added in the package of the specimens during transport. A total of 319 patients were enrolled in this study. The median specimen storage time was 132 days (range, 16 to 180 days). Of all specimens, 283 (88.7%) were culture positive by any of the three culturing systems. M. tuberculosis isolates from four contaminated specimens in all culturing systems were successfully isolated on Middlebrook 7H10 agar; thereby, the recovery rate increased to 287 (90.0%). The length of time of sputum storage had no significant effect on the rate of recovery of M. tuberculosis in all culturing systems. In conclusion, single morning sputum specimens collected at remote settings stored at −20°C for long periods of time without the addition of preservatives can yield a high recovery rate. These findings suggest a simple and cost-effective alternative method of sputum storage for epidemiological and drug resistance studies in low-resource countries. PMID:21562105

  2. Randomized dose-ranging study of the 14-day early bactericidal activity of bedaquiline (TMC207) in patients with sputum microscopy smear-positive pulmonary tuberculosis.

    PubMed

    Diacon, Andreas H; Dawson, Rodney; Von Groote-Bidlingmaier, Florian; Symons, Gregory; Venter, Amour; Donald, Peter R; Conradie, Almari; Erondu, Ngozi; Ginsberg, Ann M; Egizi, Erica; Winter, Helen; Becker, Piet; Mendel, Carl M

    2013-05-01

    Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies. PMID:23459487

  3. Randomized Dose-Ranging Study of the 14-Day Early Bactericidal Activity of Bedaquiline (TMC207) in Patients with Sputum Microscopy Smear-Positive Pulmonary Tuberculosis

    PubMed Central

    Dawson, Rodney; Von Groote-Bidlingmaier, Florian; Symons, Gregory; Venter, Amour; Donald, Peter R.; Conradie, Almari; Erondu, Ngozi; Ginsberg, Ann M.; Egizi, Erica; Winter, Helen; Becker, Piet; Mendel, Carl M.

    2013-01-01

    Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies. PMID:23459487

  4. Randomized dose-ranging study of the 14-day early bactericidal activity of bedaquiline (TMC207) in patients with sputum microscopy smear-positive pulmonary tuberculosis.

    PubMed

    Diacon, Andreas H; Dawson, Rodney; Von Groote-Bidlingmaier, Florian; Symons, Gregory; Venter, Amour; Donald, Peter R; Conradie, Almari; Erondu, Ngozi; Ginsberg, Ann M; Egizi, Erica; Winter, Helen; Becker, Piet; Mendel, Carl M

    2013-05-01

    Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies.

  5. Comparative proteomic analysis of serum diagnosis patterns of sputum smear-positive pulmonary tuberculosis based on magnetic bead separation and mass spectrometry analysis.

    PubMed

    Liu, Jiyan; Jiang, Tingting; Jiang, Feng; Xu, Dandan; Wei, Liliang; Wang, Chong; Chen, Zhongliang; Zhang, Xing; Li, Jicheng

    2015-01-01

    A major challenge in pulmonary tuberculosis (TB) control is early and accurate diagnosis of sputum smear negative pulmonary TB (SSN-PTB). The patients with SSN-PTB have to wait for a longer period of time before receiving proper treatment than sputum smear positive pulmonary TB (SSP-PTB) patients due to delay in diagnosis. The purpose of this study is to discover potential serum protein biomarkers for SSN-PTB. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from SSN-PTB patients (N = 66), SSP-PTB patients (N = 49), and healthy volunteers (N = 80). The serum protein profiles were analyzed with Biomarker Wizard system. A classification model was established using Biomarker Pattern Software (BPS). Fifty-eight protein peaks were identified to exhibit significant differences between SSN-PTB, SSP-PTB and healthy control groups (P < 0.05), among which 6 peaks were found to be down-regulated, while 10 peaks were up-regulated gradually in the healthy control, SSN-PTB, and SSP-PTB groups. Twenty-three discriminating m/z peaks were detected between SSN-PTB patients and healthy controls (P < 0.01, Fold ≥ 1.5). The classification tree combined with three protein peaks (2747.0, 4480.0, and 9410.1 Da) could distinguish SSN-PTB patients from healthy controls with a sensitivity of 83.33% and a specificity of 82.50%. Early diagnosis of SSN-PTB disease is critical in order to reduce morbidity and mortality associated with TB. The study will help to clarify the role of differential proteins in the pathogenesis of TB.

  6. Correlation between tuberculin skin test and IGRAs with risk factors for the spread of infection in close contacts with sputum smear positive in pulmonary tuberculosis

    PubMed Central

    2014-01-01

    Background The aim of the study was to assess the correlation between the tuberculin skin test (TST) and in vitro interferon-gamma released assays (IGRAs) with risk factors for the spread of infection in smear positive pulmonary tuberculosis (TB) contacts. Methods We recruited prospective contacts with smear positive pulmonary TB cases. We looked at human immunodeficiency virus (HIV) infection and other conditions of immunosuppression, presence of BCG vaccination and the degree of exposure to the index case. Patients underwent the TST, chest radiography, sputum analysis when necessary, and IGRA assays (QFN-G-IT and T-SPOT.TB). Presence of cough, diagnostic delay (days between first symptoms and TB diagnostic), contact conditions: room size (square meters) and index of overcrowding (square meters per person) were investigated in the index case. Results 156 contacts (119 adults, 37 children) of 66 TB patients were enrolled, 2.4 (1-14) contacts per TB case. The positivity of the TST did not correlate with the risk factors studied: presence of cough (p = 0.929); delayed diagnosis (p = 0.244); room size (p = 0.462); overcrowding (p = 0.800). Both QFN-G-IT and T-SPOT.TB, showed significant association with cough (p = 0.001, and p = 0.007) and room size (p = 0.020, and p = 0.023), respectively. Conclusions Both IGRA associated better than TST with certain host-related risk factors involved in the transmission of disease, such as the presence of cough. PMID:24885850

  7. Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB): a cluster-randomised trial

    PubMed Central

    Corbett, Elizabeth L; Bandason, Tsitsi; Duong, Trinh; Dauya, Ethel; Makamure, Beauty; Churchyard, Gavin J; Williams, Brian G; Munyati, Shungu S; Butterworth, Anthony E; Mason, Peter R; Mungofa, Stanley; Hayes, Richard J

    2010-01-01

    Summary Background Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission. Methods Clusters of neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits. Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to represent every cluster, and one colour allocated to each intervention group before selection began. In both groups, adult (≥16 years) residents volunteering chronic cough (≥2 weeks) had two sputum specimens collected for fluorescence microscopy. Community health workers and cluster residents were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups; analysis was by intention to treat. The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12% of randomly selected households from the two intervention groups combined; analysis was based on participants who provided sputum in the two prevalence surveys. This trial is registered, number ISRCTN84352452. Findings 46 study clusters were identified and randomly allocated equally between intervention groups, with 55 741 adults in the mobile van group and 54 691 in the door-to-door group at baseline. HIV prevalence was 21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was 2·8 per 1000 adults per year. The trial was completed as planned with no adverse events

  8. A Novel Reading Scheme for Assessing the Extent of Radiographic Abnormalities and Its Association with Disease Severity in Sputum Smear-Positive Tuberculosis: An Observational Study in Hyderabad/India

    PubMed Central

    Goyal, Surabhi; Hussain, Abid; Klassert, Tilman E.; Driesch, Dominik; Tokaryeva, Viktoriya; Löschmann, Yvonne Yi-Na; Sumanlatha, Gadamm; Ahmed, Niyaz; Valluri, Vijayalakshmi; Schumann, Ralf R.; Lala, Birgit; Slevogt, Hortense

    2015-01-01

    Background Existing reading schemes for chest X-ray (CXR) used to grade the extent of disease severity at diagnosis in patients with pulmonary tuberculosis (PTB) are often based on numerical scores that summate specific radiographic features. However, since PTB is known to exhibit a wide heterogeneity in pathology, certain features might be differentially associated with clinical parameters of disease severity. Objective We aimed to grade disease severity in PTB patients at diagnosis and after completion of DOTS treatment by developing a reading scheme based on five different radiographic manifestations and analyze their association with the clinical parameters of systemic involvement and infectivity. Methods 141 HIV-negative adults with newly diagnosed sputum smear-positive PTB were enrolled in a prospective observational study in Hyderabad, India. The presence and extent on CXRs of five radiographic manifestations, i.e., lung involvement, alveolar infiltration, cavitation, lymphadenopathy and pleural effusion, were classified using the new reading scheme by using a four-quadrant approach. We evaluated the inter-reader reliability of each manifestation, and its association with BMI and sputum smear positivity at diagnosis. The presence and extent of these radiographic manifestations were further compared with CXRs on completion of DOTS treatment. Results At diagnosis, an average lung area of 51.7% +/- 23.3% was affected by radiographic abnormalities. 94% of the patients had alveolar infiltrates, with 89.4% located in the upper quadrants, suggesting post primary PTB and in 34.8% of patients cavities were found. We further showed that the extent of affected lung area was a negative predictor of BMI (β value -0.035, p 0.019). No significant association of BMI with any of the other CXR features was found. The extent of alveolar infiltrates, along with the presence of cavitation, were strongly associated with sputum smear positivity. The microbiological cure rate in

  9. Tuberculosis (TB): Treatment

    MedlinePlus

    ... Departments & Divisions Home Conditions Tuberculosis Treating Tuberculosis Treating Tuberculosis Make an Appointment Refer a Patient Ask a ... bones is treated longer. NEXT: Preventive Treatment Diagnosing Tuberculosis History of TB Our Specialists Charles L. Daley, ...

  10. [Treatment of tuberculosis].

    PubMed

    Ben Amar, J; Dhahri, B; Aouina, H; Azzabi, S; Baccar, M A; El Gharbi, L; Bouacha, H

    2015-01-01

    The aim of this article is to give practicing physicians a practical approach to the treatment of latent and active tuberculosis. Most patients follow TB standard treatment recommended by WHO that depend on category of patient. It is a combination of four essential tuberculosis drugs of the first group: isoniazid, rifampicin, pyrazinamid and ethambutol; in some cases streptomycin can replace ethambutol. This initial phase of intensive treatment is followed by a consolidation phase. Drugs should be administered in the morning on an empty stomach one hour before meals. Treatment of latent tuberculosis (TB) infection is an important component of TB control programs. Preventive treatment can reduce the risk of developing active TB.

  11. Patient delay in the diagnosis and treatment of tuberculosis in China: findings of case detection projects

    PubMed Central

    Enarson, D. A.; Chiang, C-Y.; Rusen, I. D.; Qiu, L-X.; Kan, X-H.; Yuan, Y-L.; Du, J.; Zhang, T-H.; Li, Y.; Li, X-F.; Du, C-T.; Zhang, L-X.

    2015-01-01

    Objective: 1) To assess patient delay among new smear-positive pulmonary tuberculosis (PTB) patients in accessing health services in seven FIDELIS (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) projects from 2003 to 2008 in China; 2) to compare treatment delay by province; and 3) to assess factors associated with delay. Method: Records of new smear-positive PTB patients were reviewed. Data sources were the consultation book, laboratory register, patient record, treatment card and the PWLAHS (people with limited access to health services) evaluation form. Data were collected using a standard questionnaire, cross-checked by staff from the sites and by the International Union Against Tuberculosis and Lung Disease (The Union) and analysed by The Union. Results: Of the 75 401 new smear-positive PTB patients included in the study, 63–89% were PWLAHS. The average gross domestic product of the project sites and at national level were respectively US$557 and US$998. The median patient delay was 93 days (range 68–128). Delays were longer among females, older patients, rural residents and PWLAHS. Delayed access to health services was significantly associated with a greater number of symptoms. Conclusion: Patient delay in accessing health care in China was lengthy; TB care and control needs to be improved. PMID:26400603

  12. Treatment outcome of tuberculosis patients at Gondar University Teaching Hospital, Northwest Ethiopia. A five - year retrospective study

    PubMed Central

    Tessema, Belay; Muche, Abebe; Bekele, Assegedech; Reissig, Dieter; Emmrich, Frank; Sack, Ulrich

    2009-01-01

    Background In Gondar University Teaching Hospital standardized tuberculosis prevention and control programme, incorporating Directly Observed Treatment, Short Course (DOTS) started in 2000. According to the proposal of World Health Organization (WHO), treatment outcome is an important indicator of tuberculosis control programs. This study investigated the outcome of tuberculosis treatment at Gondar University Teaching Hospital in Northwest Ethiopia. Methods We analyzed the records of 4000 tuberculosis patients registered at Gondar University Teaching Hospital from September 2003 to May 2008. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control program guideline. Multivariate analysis using logistic regression model was used to analyse the association between treatment outcome and potential predictor variables. Results From the total of 4000 patients, tuberculosis type was categorized as extrapulmonary in 1133 (28.3%), smear negative pulmonary tuberculosis in 2196 (54.9%) and smear positive pulmonary tuberculosis in 671 (16.8%) cases. Of all patients, treatment outcome was classified as successfully treated in 1181(29.5%), defaulted in 730 (18.3%), died in 403 (10.1%), treatment failed in six (0.2%) and transferred out in 1680 (42.0%) patients. Males had the trend to be more likely to experience death or default than females, and the elderly were more likely to die than younger. The proportion of default rate was increased across the years from 97(9.2%) to 228(42.9%). Being female, age group 15-24 years, smear positive pulmonary tuberculosis and being urban resident were associated with higher treatment success rate. Conclusion The treatment success rate of tuberculosis patients was unsatisfactorily low (29.5%). A high proportion of patients died (10.1%) or defaulted (18.3%), which is a serious public health concern that needs to be addressed urgently. PMID:19799801

  13. COBAS® TaqMan® MTB, smear positivity grade and MGIT culture; correlation analyses of three methods for bacillary quantification.

    PubMed

    Chikamatsu, Kinuyo; Aono, Akio; Kato, Tomoko; Takaki, Akiko; Yamada, Hiroyuki; Sasaki, Yuka; Izumi, Kiyohiko; Yi, Lina; Mitarai, Satoshi

    2016-01-01

    We investigated the correlation between the cycle threshold (Ct) value of the COBAS(®) TaqMan(®) MTB (TaqMan MTB), the mycobacterial smear positivity grade, and the time to detection (TTD) in the Mycobacteria Growth Indicator Tube (MGIT) for quantification of Mycobacterium tuberculosis (MTB). For 57 sputum samples, significant correlations were observed between the Ct value, the smear positivity grade, and the MGIT TTD (Spearman's rank correlation coefficient: r(s) = -0.940, P < 0.001 and Pearson's correlation coefficient: r(p) = 0.737, P < 0.001). In addition, a correlation was observed between the number of bacteria estimated based on the smear positivity grade and the number of MTB bacilli calculated by the Ct value (r(s) = 0.930, P < 0.001). This study has demonstrated the possible estimation of the smear positivity grade and MGIT TTD using the Ct value of TaqMan MTB, which is based on a real-time PCR system, for diagnostic samples.

  14. Sublineages of Mycobacterium tuberculosis Beijing genotype strains and unfavorable outcomes of anti-tuberculosis treatment.

    PubMed

    Hang, Nguyen T L; Maeda, Shinji; Keicho, Naoto; Thuong, Pham H; Endo, Hiroyoshi

    2015-05-01

    The influence of Mycobacterium tuberculosis (MTB) lineages/sublineages on unfavorable tuberculosis (TB) treatment outcomes is poorly understood. We investigated the effects of Beijing genotype sublineages and other factors contributing to treatment outcome. Patients newly diagnosed with sputum smear-positive and culture-positive TB in Hanoi, Vietnam, participated in the study. After receiving anti-TB treatment, they were intensively followed up for the next 16 months. MTB isolates collected before treatment were subjected to drug susceptibility testing, and further analyzed to determine MTB (sub) lineages and their clonal similarities. Of 430 patients, 17 had treatment failure and 30 had TB recurrence. Rifampicin resistance was associated with treatment failure {adjusted odds ratio = 6.64 [95% confidence interval (CI), 1.48-29.73]}. The modern Beijing genotype was significantly associated with recurrent TB within 16 months [adjusted hazard ratio = 3.29 (95% CI, 1.17-9.27)], particularly after adjustment for the relevant antibiotic resistance. Human immunodeficiency virus coinfection and severity on chest radiographs were not significantly associated with unfavorable outcomes. Our findings provide further understanding of the influence of MTB strains on unfavorable treatment outcomes. Multiple risk factors should be considered for the optimal management of TB. PMID:25732626

  15. Directly Observed Treatment Short-course (DOTS) for tuberculosis control program in Gambella Regional State, Ethiopia: ten years experience

    PubMed Central

    2014-01-01

    Background Tuberculosis is still the leading cause of illness in the world which accounted for 2.5% of the global burden of disease, and 25% of all avoidable deaths in developing countries. The aim of study was to assess impact of DOTS strategy on tuberculosis case finding and treatment outcome in Gambella Regional State, Ethiopia from 2003 up to 2012 and from 2002 up to 2011, respectively. Methods Health facility-based retrospective study was conducted. Data were collected and reported in quarterly basis using WHO reporting format for TB case finding and treatment outcome from all DOTS implementing health facilities in all zones of the region to Federal Ministry of Health. Results A total of 10024 all form of TB cases had been registered between the periods from 2003 up to 2012. Of them, 4100 (40.9%) were smear-positive pulmonary TB, 3164 (31.6%) were smear-negative pulmonary TB and 2760(27.5%) had extra-pulmonary TB. Case detection rate of smear-positive pulmonary TB had increased from 31.7% to 46.5% from the total TB cases and treatment success rate increased from 13% to 92% with average mean value of being 40.9% (SD = 0.1) and 55.7% (SD = 0.28), respectively for the specified year periods. Moreover, the average values of treatment defaulter and treatment failure rates were 4.2% and 0.3%, respectively. Conclusion It is possible to achieve the recommended WHO target which is 70% of CDR for smear-positive pulmonary TB, and 85% of TSR as it was already been fulfilled the targets for treatments more than 85% from 2009 up to 2011 in the region. However, it requires strong efforts to enhance case detection rate of 40.9% for smear-positive pulmonary TB through implementing alternative case finding strategies. PMID:24444379

  16. Adherence to anti-tuberculosis treatment in Tigray, Northern Ethiopia

    PubMed Central

    Teklu, T.; Desalegn, F.; Tesfay, M.; Klinkenberg, E.; Mulugeta, A.

    2014-01-01

    Setting: Tuberculosis (TB) patients in Mekelle Zone, Tigray Region, in Ethiopia. Objective: To investigate adherence to anti-tuberculosis treatment. Design: A cross-sectional study in health facilities providing anti-tuberculosis treatment was conducted. Adherence was measured in three ways: through self-reported missed doses, by visual analogue scale whereby patients rate their own adherence and by record review. A patient was considered to be adherent if 90% or more of the prescribed medication was taken. Result: Of 278 TB patients included, 101 were in the intensive and 177 in the continuation phase. Respectively 67 (24.1%), 130 (46.8%) and 80 (28.8%) patients had smear-positive, smear-negative and extra-pulmonary TB. Self-report of missed doses and record review indicated adherence of respectively 273 (97.3%) and 271 (97.5%) patients. By visual analogue scale, 250 (91.6%) patients rated themselves as adherent. History of drug side effects (aOR 0.25, 95%CI 0.08–0.77) and knowledge about TB prevention (aOR 0.19, 95%CI 0.05–0.8) were independently associated with being adherent in this setting. Conclusion: Adherence to anti-tuberculosis treatment was high in our study. Adherence support should be given to the poor, the elderly, patients co-infected with the human immunodeficiency virus, alcohol abusers and smokers. Health education on TB prevention should be given to all TB patients regularly. PMID:26478511

  17. HIV testing and tuberculosis treatment outcome in a rural district in Malawi.

    PubMed

    Banerjee, A; Moyo, S; Salaniponi, F; Harries, A

    1997-01-01

    Unusually high mortality rates have been recorded among HIV-infected tuberculosis patients in urban Africa 6 and 12 months after initiation of tuberculosis treatment--a trend that impedes efforts to achieve the 85% cure rate target set by the World Health Organization. This study investigated tuberculosis treatment outcomes in relation to HIV serostatus in a rural district of Malawi (Ntcheu). All 205 smear-positive pulmonary tuberculosis patients newly diagnosed in the district in 1995 received 2 months of daily supervised streptomycin, rifampicin, isoniazid, and pyrazinamide in the hospital followed by 6 months of isoniazid and thiacetazone at home. HIV testing, offered to all tuberculosis patients, was accepted by 110 (54%), 73 (66%) of whom were HIV-positive. By the end of treatment, 126 patients (61%) had been cured and 56 (27%) had died. Significantly fewer HIV-positive patients or patients who declined HIV testing were cured (59% and 55%, respectively) than those who agreed to testing and were HIV-negative (84%). The mortality rate was 29% among patients who tested HIV-positive, 8% among those with a negative test result, and 34% among patients who declined HIV testing. Acceptance of HIV testing improved over the course of the study period in response to changes in counseling techniques, especially clarification that blood taken for HIV testing would not be used for transfusions. Overall, these findings suggest that, in areas where HIV infection is prevalent, an 85% tuberculosis cure rate may be unrealistic.

  18. Treatment of multidrug-resistant tuberculosis in China.

    PubMed

    Zhang, L X

    1996-01-01

    During the past decade the number and gravity of tuberculosis (TB) cases has continued to increase, both in developing and industrialized nations. Coupled with the recent emergence of multidrug-resistant tuberculosis (MDR-TB), the possibility that untreatable forms of the disease may become widespread has arisen. In China, the prevalence rate of smear-positive cases from three national surveys in 1979, 1984-1985 and 1990 was 187, 156 and 134/100,000, respectively, thus giving an annual average reduction rate of only 3.0%. This may be due to the accumulation of chronic cases, which is not surprising given that as many as 84.3% of new smear-positive cases received non-organized chemotherapy. To counteract this situation, a strategy was developed in Beijing to practice fully supervised chemotherapy for all new smear-positive cases. This is now 90% with a cure rate also of 90%. As a result, the prevalence rate of smear-positive cases has dropped, with an average annual reduction of 17%. Building upon this success, the World Bank Loan TB Control Project in China has been carried out in 12 provinces with 550 million people since 1992. The main objective of this project is to provide fully supervised, 6-month short-course chemotherapy for all newly detected smear-positive cases. The cure rate based on cohort analysis was 88% in 1993. Complete data are not available on resistance although the initial and acquired resistance rates were 28.1 and 41.1%, respectively. MDR-TB treated with ofloxacin has been increasing since 1992, with 317 cases reported during the period 1992-1995, of which 77% showed sputum conversion.

  19. Effectiveness of a community-based observation of anti-tuberculosis treatment in Bangalore City, India, 2010-2011

    PubMed Central

    Kumar, P.; Sagili, K. D.; Enarson, D. A.

    2013-01-01

    Setting: The Revised National Tuberculosis Control Programme in an urban setting of Bangalore City, India. Objectives: To compare treatment outcomes and smear conversion rates among new smear-positive tuberculosis (TB) patients undergoing treatment administered by community directly observed treatment (DOT) providers with those undergoing treatment administered by institutional DOT providers in Bangalore City in 2010-2011. Method: Cohort study of routine data recorded from treatment cards of TB patients undergoing treatment under the public health services from 1 October 2010 to 30 September 2011. Result: Treatment records of 1864 new smear-positive TB patients registered during this period were evaluated. Among those evaluated, 604 (32%) had been administered treatment by community DOT providers and the remainder by institutional DOT providers. The treatment success rate in those undergoing community DOT was 93% (n = 564) and that of those undergoing institutional DOT was 75% (n = 951; RR 1.23, 95%CI 1.19-1.28). The sputum smear conversion rate of patients who underwent community DOT was 92% and that of those who underwent institutional DOT was 71% at the end of 2 months. Conclusion: We conclude that community DOT for treatment supervision of TB patients is more effective than institutional DOT and that it should be reinforced. PMID:26393035

  20. Epidemiology of tuberculosis and evaluation of treatment outcomes in the national tuberculosis control programme, River Nile state, Sudan, 2011-2013.

    PubMed

    Elmadhoun, W M; Noor, S K; Bushara, S O; Ahmed, E O; Mustafa, H; Sulaiman, A A; Almobarak, A O; Ahmed, M H

    2016-04-28

    Tuberculosis is a major health problem in Sudan, a country that carries 11-15% of the tuberculosis burden in the Eastern Mediterranean Region. This study aimed to describe the epidemiology of tuberculosis in River Nile State and to compare treatment outcomes with WHO recommended indicators. A descriptive study was conducted on data collected from records of 1221 patients registered at tuberculosis management units over the 3 years 2011-2013. The mean age of cases was 37.7 (SD 21.5) years and 65.9% were males; 76.3% were pulmonary tuberculosis and 36.9% were sputum smear-positive cases. Average values for all outcome indicators were suboptimal, notably rates of case notification (30.8 per 100 000), case detection (10.3%), treatment success (79.6%), treatment failure (3.0%), default (8.1%) and death (8.0%). Of the 264 patients tested for HIV, 3.8% were positive. Outcome indicators for the national tuberculosis control programme are lagging behind the required targets.

  1. Treatment outcomes of various types of tuberculosis in Pakistan, 2006 and 2007.

    PubMed

    Chughtai, A A; MacIntyre, C R; Wang, Y A; Gao, Z; Khan, W

    2013-06-01

    Measuring treatment outcome is important for successful tuberculosis (TB) control programmes. The purpose of this study was to examine the outcomes of various types of TB cases registered in Pakistan over a 2-year period and compare those outcomes among the different provinces and regions of the country. A retrospective, cohort study was conducted in which TB treatment outcome reports were reviewed. Of the 349 694 pulmonary TB cases registered in Pakistan during 2006 and 2007, 309154 (88.4%) were treated successfully. Treatment success was significantly higher in new smear-positive cases and lower in retreatment cases. Among the provinces and regions, treatment success was significantly higher in 4 out of 8 provinces. Treatment success needs to be improved, particularly in retreatment cases. The national TB control programme should review the provincial and regional programmes and learn lessons from well-performing programmes. Patient factors that may affect the treatment outcome should be also studied.

  2. Impact of Community-Based DOT on Tuberculosis Treatment Outcomes: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, HaiYang; Ehiri, John; Yang, Huan; Tang, Shenglan; Li, Ying

    2016-01-01

    Background Poor adherence to tuberculosis (TB) treatment can lead to prolonged infectivity and poor treatment outcomes. Directly observed treatment (DOT) seeks to improve adherence to TB treatment by observing patients while they take their anti-TB medication. Although community-based DOT (CB-DOT) programs have been widely studied and promoted, their effectiveness has been inconsistent. The aim of this study was to critical appraise and summarize evidence of the effects of CB-DOT on TB treatment outcomes. Methods Studies published up to the end of February 2015 were identified from three major international literature databases: Medline/PubMed, EBSCO, and EMBASE. Unpublished data from the grey literature were identified through Google and Google Scholar searches. Results Seventeen studies involving 12,839 pulmonary TB patients (PTB) in eight randomized controlled trials (RCTs) and nine cohort studies from 12 countries met the criteria for inclusion in this review and 14 studies were included in meta-analysis. Compared with clinic-based DOT, pooled results of RCTs for all PTB cases (including smear-negative or -positive, new or retreated TB cases) and smear-positive PTB cases indicated that CB-DOT promoted successful treatment [pooled RRs (95%CIs): 1.11 (1.02–1.19) for all PTB cases and 1.11 (1.02–1.19) for smear-positive PTB cases], and completed treatment [pooled RRs (95%CIs): 1.74(1.05, 2.90) for all PTB cases and 2.22(1.16, 4.23) for smear-positive PTB cases], reduced death [pooled RRs (95%CIs): 0.44 (0.26–0.72) for all PTB cases and 0.39 (0.23–0.66) for smear-positive PTB cases], and transfer out [pooled RRs (95%CIs): 0.37 (0.23–0.61) for all PTB cases and 0.42 (0.25–0.70) for smear-positive PTB cases]. Pooled results of all studies (RCTs and cohort studies) with all PTB cases demonstrated that CB-DOT promoted successful treatment [pooled RR (95%CI): 1.13 (1.03–1.24)] and curative treatment [pooled RR (95%CI): 1.24 (1.04–1.48)] compared with

  3. Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

    PubMed Central

    Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.

    2011-01-01

    Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732

  4. Delays to treatment and out-of-pocket medical expenditure for tuberculosis patients, in an urban area of South America.

    PubMed

    Lambert, M-L; Delgado, R; Michaux, G; Volz, A; Speybroeck, N; Van Der Stuyft, P

    2005-12-01

    Short delays to treatment are important for the control of tuberculosis (TB). National Tuberculosis Programmes provide free diagnosis and treatment for smear-positive patients, so that the patients' out-of-pocket medical expenditure could be almost nil. The factors associated with delays in starting treatment, and the pre-treatment out-of-pocket medical expenditure for TB patients, have now been investigated in the Bolivian city of Cochabamba. Bolivia is the Latin American country with the highest incidence of TB. It is covered by a national TB programme that provides free diagnosis and free treatment for smear-positive patients. Structured interviews with 144 smear-positive patients enrolled in this programme revealed median patient, provider and total delays of 3.6, 6.2 and 12.9 weeks, respectively. The total delays were longer for the female patients than for the male, and for patients who consulted private doctors than for the other patients. When the first healthcare provider was a doctor, the median provider delay was 4.9 weeks in the public sector but 7.2 weeks in the private. The median out-of-pocket medical expenditure per patient, which was U.S.$13.2 overall, was much higher for those who consulted a private doctor than for those who did not (U.S.$21.9 v. U.S.$5.4, respectively; P<0.001). It appears that interventions targeting doctors (in both the private and public sectors) are likely to have a larger impact on the shortening of delays in TB treatment than interventions targeting patients. They could also reduce unnecessary out-of-pocket expenditure.

  5. Burden of tuberculosis in Kampala, Uganda.

    PubMed Central

    Guwatudde, David; Zalwango, Sarah; Kamya, Moses R.; Debanne, Sara M.; Diaz, Mireya I.; Okwera, Alphonse; Mugerwa, Roy D.; King, Charles; Whalen, Christopher C.

    2003-01-01

    OBJECTIVE: To determine the prevalence and incidence of tuberculosis in one of Uganda's poor peri-urban areas. METHODS: Multi-stage sampling was used to select a sample of households whose members were evaluated for presence of signs and/or symptoms of active tuberculosis; history of tuberculosis treatment; and relevant demographic, socioeconomic, and household environment characteristics. Patients with suspected tuberculosis underwent standardized evaluation for active disease. FINDINGS: A sample of 263 households with 1142 individuals was evaluated. Nineteen people were classified as having had tuberculosis during the one-year reference period (May 2001-April 2002): nine (47%) cases already had been diagnosed through the health care system, while 10 cases (53%) were diagnosed through the survey. The prevalences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 14.0 (95% confidence interval (CI) 7.8-20.3) and 4.4 (CI = 0.83-7.89) per thousand, respectively. The incidences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 9.2 (CI = 3.97-14.4) and 3.7 (CI = 0.39-6.95) per thousand per year, respectively. CONCLUSION: The rate of tuberculosis in this peri-urban community was exceptionally high and may be underestimated by current surveillance systems. The need for interventions aimed at reducing tuberculosis transmission in this, and other similar communities with high case rates, is urgent. PMID:14758406

  6. The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis.

    PubMed Central

    Blomberg, B.; Spinaci, S.; Fourie, B.; Laing, R.

    2001-01-01

    There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a result of inappropriate drug selection and monotherapy. Only FDCs of proven quality and proven rifampicin bioavailability should be purchased and used. In most situations, blood levels of the drugs are inadequate because of poor drug quality rather than poor absorption. This is true irrespective of the human immunodeficiency virus (HIV) infection status of the tuberculosis patients (other than those with overt acquired immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently, WHO, IUATLD and their partners are developing strategies for ensuring that only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs). PMID:11217670

  7. Directly-Observed and Self-Administered Tuberculosis Treatment in a Chronic, Low-Intensity Conflict Setting in India

    PubMed Central

    Das, Mrinalini; Isaakidis, Petros; Armstrong, Edward; Gundipudi, Nirmala Rani; Babu, Ramesh B.; Qureshi, Ihtesham A.; Claes, Andrea; Mudimanchi, Anil Kumar; Prasad, Nagendra; Mansoor, Homa; Abraham, Sunita

    2014-01-01

    Background Limited data are available about tuberculosis treatment models of care for internally displaced populations in chronic, low-intensity conflict zones. This study aimed to detail experiences of a Médecins Sans Frontières tuberculosis programme in Andhra Pradesh-Chhattisgarh border area, India, from January to December 2012. Methods The study was a description of two retrospective, observational cohorts receiving category I tuberculosis treatment, either intermittent directly observed treatment (DOT) or daily self-administered therapy (SAT) depending on the security of the area and access to health care services. Results A total of 55 and 17 new tuberculosis patients under DOT and SAT respectively, with complete outcomes were included in the study. Most patients registered were new cases suffering from pulmonary, smear-positive tuberculosis. More than half of the patients in both cohorts were cured or completed treatment: 38/55 (69%) patients were successfully treated under DOT compared to 9/17 (53%) under SAT. Of the patients with adverse outcomes, the ratios of loss to follow up: failure: died were 10∶4:3 under DOT and 7∶0:1 under SAT. A much smaller proportion of patients under DOT (18%) were lost to follow up than under SAT (41%). Discussion Maximum efforts are required to implement successful tuberculosis control programmes for internally displaced populations in conflict zones. Our study suggests that complete tuberculosis treatment can be given to patients using either intermittent DOT or daily SAT, depending on security and access to health services. National TB programmes should include SAT strategies for tuberculosis treatment as these may be an alternative feasible option in conflict settings. PMID:24651176

  8. Treatment default and death among tuberculosis patients in Hunan, China.

    PubMed

    Abuaku, Benjamin; Tan, Hongzhuan; Li, Xingli; Chen, Mengshi; Huang, Xin

    2010-04-01

    We used the 2005 and 2006 national surveillance data to elucidate some of the risk factors for treatment default and death among tuberculosis (TB) patients in Hunan, China. Risk of default was higher in males (odds ratio (OR) 1.25; 95% confidence interval (CI) 1.08, 1.44); lowest in patients aged 15-24 y (OR 0.60; 95% CI 0.49, 0.75), and generally increased with increasing age; lower in patients living in cities with per capita gross domestic product (GDP) of less than 1000 US$ (OR 0.60, 95% CI 0.49, 0.72), and increased with increasing per capita GDP of city of residence; and higher in patients with previously treated smear-positive pulmonary TB (diagnostic category II according to the World Health Organization definition; OR 1.99; 95% CI 1.22, 3.23). Risk of death was lowest in patients aged 15-24 y (OR 0.07; 95% CI 0.05, 0.10), and increased with increasing age; lower in new cases (OR 0.50; 95% CI 0.33, 0.76); and highest in patients who treated themselves (OR 3.47; 95% CI 1.27, 9.46). We conclude that male TB patients, elderly TB patients, patients resident in cities with higher per capita GDP, and patients receiving category II treatment need special attention to reduce TB treatment default in the province. Furthermore, elderly TB patients and patients with a long history of TB need special attention to reduce mortality. Self-treatment also needs to be discouraged to reduce mortality.

  9. Short-term and long-term outcomes following DOTS-based treatment for tuberculosis patients in Burkina Faso

    PubMed Central

    Kouanda, S.; Nikiéma, L.; Ouédraogo, G.; Tiendrébeogo, S.; Sondo, B.; Greenwell, F.; Salomon, J. A.

    2012-01-01

    A cross-sectional study was initiated in Burkina Faso’s National Tuberculosis Programme to confirm successful treatment results within 3 months of completing treatment and to characterise longer-term outcomes 12–24 months after completion. The sample (n = 278) included 91 patients who had completed treatment 0–3 months earlier (‘short-term’ sample) and 187 patients who had completed treatment 12–24 months earlier (‘long-term’ sample). All sputum specimens from the short-term sample were confirmed as negative. In the long-term sample, among 154 patients with available information, 13 (8%) had died, 24 were not traced, and 117 (76%) were interviewed and had sputum examinations, of which 2 (2%) were smear-positive. Recording of successful treatment outcomes shows good validity. PMID:26392942

  10. DOTS-based tuberculosis treatment and control during civil conflict and an HIV epidemic, Churachandpur District, India.

    PubMed Central

    Rodger, Alison J.; Toole, Mike; Lalnuntluangi, Baby; Muana, V.; Deutschmann, Peter

    2002-01-01

    OBJECTIVE: To pilot the WHO guidelines on DOTS for tuberculosis (TB) among displaced people affected by conflict in Churachandpur District, Manipur State, north-east India, which has endured an HIV epidemic, injecting drug use, civil unrest, high levels of TB, and poor TB treatment and prevention services for many years. METHODS: Prerequisites for TB control programmes were established. WHO guidelines and protocols were adapted for local use. Outreach workers were appointed from each ethnic group involved in the conflict, and training was conducted. Quality control and evaluation processes were introduced. FINDINGS: TB was diagnosed in 178 people between June and December 1998. Of the 170 with pulmonary disease, 85 were smear-positive. Successful outcomes were recorded in 91% of all patients and in 86% of smear-positive cases of pulmonary TB. The default rate and the mortality rate were low at 3% each. HIV positive serostatus was the only factor associated with a poor treatment outcome. CONCLUSION: TB treatment and control were possible in a conflict setting and WHO targets for cure were attainable. The factors associated with the success of the programme were strong local community support, the selection of outreach workers from each ethnic group to allow access to all areas and patients, the use of directly observed therapy three times a week instead of daily in the interest of increased safety, and the limiting of distances travelled by both outreach workers and patients. PMID:12132001

  11. Treatment delay among pulmonary tuberculosis patients in pastoralist communities in Bale Zone, Southeast Ethiopia

    PubMed Central

    2012-01-01

    Background Tuberculosis (TB) is a major public health problem in Africa with Ethiopia being the most affected. Treatment delay is an important indicator of access to TB diagnosis and treatment. However, little is known about factors associated with treatment delay of pulmonary TB among pastoralists. Health facility based cross sectional study was conducted on 129 pulmonary TB patients in pastoralist community. The study was conducted in three health centers and a hospital. Time between onset of TB symptoms and first visit to a professional health care provider (patient delay), and the time between first visits to the professional health care provider to the date of diagnosis (provider's delay) were analyzed using SPSS 16.0 statistical software. Findings A total of 129 new smear positive pulmonary TB patients participated in the study. The median total delay was 97 days. The median patient and health provider delays were 63 and 34 days, respectively. Ninety six percent of the patients were delayed for more than the twenty one days cutoff point. Patient delay was positively associated with first visit to traditional healer/private clinic/drug shop, rural residence, being illiterate, living in more than 10 kilometers from health facility; severity of illness at first presentation to health facility. Provider delay was positively associated with rural residence, being illiterate, patient with good functional status, patients in contact with more than two health providers, and place of first visit being traditional healer/private clinic/drug shop. Conclusions This study showed that majority of smear positive patients delayed either for diagnosis or treatment, thus continue to serve as reservoirs of infection. This indicates that there is a need for intervention to decrease patient and provider delays. Effort to reduce delays in pastoralist communities should focus on improving access to services in rural communities, engaging traditional and private health providers and

  12. [Treatment of extrapulmonary tuberculosis and complicated forms of pulmonary tuberculosis].

    PubMed

    2008-09-01

    Tuberculosis is one of the most important health problems worldwide. In developed countries there is an increased number of cases due to different reasons. The most likely determinant cause is from immigrants coming from high endemic areas. This phenomenon is a direct cause of the increase in extrapulmonary and complicated pulmonary forms of tuberculosis. There are only a few controlled clinical trials evaluating therapies for extrapulmonary tuberculosis. Consequently, documented evidence is scarce, particularly in paediatrics. The majority of therapeutic recommendations are based on series of cases or expert opinions, with a lack of uniformity provided by the different consensus of the main scientific societies. The main objective of this fourth consensus by the Tuberculosis Study Group of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediátrica, SEIP) is to perform a thorough revision of the data obtained from scientific literature, in order to establish recommendations for the treatment of extrapulmonary tuberculosis and complicated forms of pulmonary tuberculosis, adapted to the characteristics and drugs available in Spain.

  13. Tuberculosis case--finding and treatment in the central prison of Qazvin province, Islamic Republic of Iran.

    PubMed

    Assefzadeh, M; Barghi, R Gh; Shahidi, Sh S

    2009-01-01

    As a part of a comprehensive programme of tuberculosis (TB) control in the central prison in Qazvin, Islamic Republic of Iran, a programme of active case-finding was carried out from February 2004 to July 2005. From the 768 prisoners examined, 41 (5.3%) were suspected of TB and gave sputum samples. A total of 7 smear-positive TB cases were found, giving a TB prevalence in the prison of 910 per 100,000, 113 times the total TB prevalence in Qazvin province in the same year. From 7 diagnosed and treated patients, 4 were cured with the category 1 standard regimen, 1 completed treatment and 2 failed to complete treatment. Improvements are needed in TB case recognition of prisoners, especially newcomers.

  14. Can Follow-Up Examination of Tuberculosis Patients Be Simplified? A Study in Chhattisgarh, India

    PubMed Central

    Kundu, Debashish; M. V. Kumar, Ajay; Satyanarayana, Srinath; Dewan, Puneet Kumar; Achuthan Nair, Sreenivas; Khaparde, Kshitij; Nayak, Priyakanta; Van den Bergh, Rafael; Manzi, Marcel; Enarson, Donald A.; Deshpande, Madhav Rao; Chandraker, Sachin

    2012-01-01

    Background Each follow-up during the course of tuberculosis treatment currently requires two sputum examinations. However, the incremental yield of the second sputum sample during follow-up of different types of tuberculosis patients has never been determined precisely. Objectives To assess the incremental yield of the second sputum sample in the follow-up of tuberculosis patients under the Revised National Tuberculosis Control Programme (RNTCP) in Chhattisgarh, India. Methodology A record review of tuberculosis (TB) patients registered in 2009 using a structured proforma from two sources, Tuberculosis and Laboratory Register, was undertaken in the six districts of Chhattisgarh, India. Results In smear positive cases, of 10,048 follow-up examinations, 45 (0.5%) were found to be smear positive only on the second sputum when the result of the first sample was negative. In smear negative pulmonary and extra pulmonary TB patients, of 6,206 follow-up smear examinations, 11(0.2%) were found to be smear positive. Conclusions The incremental yield of a second smear examination was very low, indicating that examination of one sputum sample is enough during follow-up among TB patients. There is insufficient yield to support sputum smear microscopy for monitoring smear negative pulmonary TB and extra pulmonary TB patients. These results indicate that the follow-up smear microscopy can be substantially simplified with favourable resource implications. PMID:23227230

  15. Drug-resistant tuberculosis: emerging treatment options

    PubMed Central

    Adhvaryu, Meghna; Vakharia, Bhasker

    2011-01-01

    Multidrug-resistant tuberculosis has emerged worldwide, with an increasing incidence due to failure of implementation of apparently effective first-line antituberculous therapy as well as primary infection with drug-resistant strains. Failure of current therapy is attributed to a long duration of treatment leading to nonadherence and irregular therapy, lack of patient education about the disease, poverty, irregular supply by care providers, drug–drug interactions in patients coinfected with human immunodeficiency virus (HIV), inadequate regulations causing market overlap and irresponsible drug usage in the private sector, and lack of research, with no addition of new drugs in the last four decades. Present standards of care for the treatment of drugsusceptible tuberculosis, multidrug-resistant tuberculosis, tuberculosis-HIV coinfection, and latent tuberculosis infection are all unsatisfactory. Since 2000, the World Health Organization (WHO) has focused on drug development for tuberculosis, as well as research in all relevant aspects to discover new regimens by 2015 and to eliminate tuberculosis as a public health concern by 2050. As a result, some 20 promising compounds from 14 groups of drugs have been discovered. Twelve candidates from eight classes are currently being evaluated in clinical trials. Ongoing research should prioritize identification of novel targets and newer application of existing drugs, discovery of multitargeted drugs from natural compounds, strengthening host factors by immunopotentiation with herbal immunomodulators, as well as protective vaccines before and after exposure, consideration of surgical measures when indicated, development of tools for rapid diagnosis, early identification of resistant strains, and markers for adequacy of treatment and an integrative approach to fulfill WHO goals. However, regulatory control over the drug market, as well as public-private partnership to use health program facilities to track patients and ensure

  16. High tuberculosis treatment success in Kabul, Afghanistan despite high patient transfers out.

    PubMed

    Zhuben, M; Delawer, F M; Andar, A H; Salimi, F; Ngamvithayapong-Yanai, J

    2013-08-01

    The National Tuberculosis (TB) Institute has the highest patient transfer-out rate in Afghanistan, but the result and treatment outcome of transferred patients were unknown in 2009. This operational research investigated the characteristics and treatment outcome of all transferred-out patients living in Kabul province. We analysed the 1-year TB register of the Institute (n = 1180 cases) and visited 24 health centres to review their TB registers. The results show the transfer-out rate was 52.6%. Of the transferred cases, 58.6% were women and 61.8% pulmonary TB cases (smear-positive 70.6%). The arrival rates of transfer-out patients at health centres in Kabul province were 87.6% for both men and women. Males aged 21-40 years were the most likely to be nonarrivals (OR = 8.91; 95% CI: 1.55-66.7). Treatment success rates in female and male patients were 84.4% and 77.5% respectively and default rates were 7.8% and 18.3%. Strategies to reduce the non-arrival to health centres and treatment interruption in male patients aged 20-40 years are warranted.

  17. Clinical Features and Treatment Outcomes of Patients with Drug-Resistant and Drug-Sensitive Tuberculosis: A Historical Cohort Study in Porto Alegre, Brazil

    PubMed Central

    Micheletti, Vania Celina Dezoti; Kritski, Afrânio Lineu; Braga, José Ueleres

    2016-01-01

    Purpose To evaluate the clinical features and treatment outcomes of patients with pulmonary tuberculosis, stratified by level of drug resistance. Methods This was a historical cohort study based on data from the II National Anti-Tuberculosis Drug Resistance Survey (2006–2007) collected at eight participating health care facilities in Porto Alegre, southern Brazil. The cohort was followed for 3 years after the start of treatment. Results Of 299 cases of smear-positive pulmonary tuberculosis included in the study, 216 (72.2%) were diagnosed at five public primary health care units and 83 (27.8%) at three public hospitals. Among these cases, the prevalence of drug-resistant tuberculosis was 14.4%, and that of multidrug-resistant tuberculosis was 4.7%. Overall, 32.0% of drug-resistant and 2.0% of multidrug-resistant cases occurred in previously treated patients. The most common comorbidity in the sample was HIV infection (26.2%). There was no association between drug-resistant or multidrug-resistant tuberculosis and sociodemographic variables. Cure was achieved in 66.7% of patients, and the default rate was 21.2%. The 2-month sputum conversion rate was 34.2%, and the relapse rate was 16.9%. Patients with drug-resistant tuberculosis had lower rates of cure (45.2%) and 2-month sputum conversion (25%), as well as a higher relapse rate (30.7%). Conclusion These results highlight the urgent need for a more effective TB control program in this geographical setting, with a major emphasis on treatment of drug-resistant and multidrug-resistant tuberculosis. PMID:27505633

  18. Treatment of Tuberculosis. A Historical Perspective.

    PubMed

    Murray, John F; Schraufnagel, Dean E; Hopewell, Philip C

    2015-12-01

    Of all achievements in medicine, the successful treatment of tuberculosis has had one of the greatest impacts on society. Tuberculosis was a leading cause of disease and a mortal enemy of humanity for millennia. The first step in finding a cure was the discovery of the cause of tuberculosis by Robert Koch in 1882. The sanatorium movement that began shortly afterward in Europe, and soon spread to the United States, brought attention to the plight of afflicted persons, and catalyzed public health action. The antituberculosis benefit of streptomycin was announced in 1945, although application was limited by the rapid development of resistance. para-Aminosalicylic acid, also discovered in 1945, when combined with streptomycin was found to greatly reduce the occurrence of drug resistance. In 1952, isoniazid opened the modern era of treatment; it was inexpensive, well tolerated, and safe. In the early 1960s, ethambutol was shown to be effective and better tolerated than para-aminosalicylic acid, which it replaced. In the 1970s, rifampin found its place as a keystone in the therapy of tuberculosis. The use of rifampin enabled the course of treatment to be reduced to nine months. Incorporation of pyrazinamide into the first-line regimen led to a further reduction of treatment duration to six months. Treatment of multiple drug-resistant tuberculosis remains a difficult problem requiring lengthy treatment with toxic drugs. However, shortened regimens show promise, and two new drugs, bedaquiline and delamanid, have demonstrated effectiveness in preliminary studies and are being used for extensively drug-resistant tuberculosis.

  19. [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment].

    PubMed

    Baquero-Artigao, F; Mellado Peña, M J; del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

    2015-10-01

    In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended.

  20. [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment].

    PubMed

    Baquero-Artigao, F; Mellado Peña, M J; del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

    2015-10-01

    In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended. PMID:25754314

  1. [Tuberculosis in Asia].

    PubMed

    2002-10-01

    populations. These factors pose particular problems for implementing DOTS in various ways. Socio-cultural and environmental factors are particularly important in Nepal, and several measures have been developed to overcome these difficulties. One is active community participation through the DOTS committee. The committee consists of a group of motivated people, including social workers, political leaders, health services providers, journalists, teachers, students, representatives of local organizations, medical schools and colleges, industries, private practitioners, and TB patients. One DOTS committee is formed in every treatment center. A key role of the DOTS committee is to identify local problems and their solutions. It increases public awareness about TB and DOTS; supports people with TB in the community by providing treatment observers and tracing late patients; and encourages cooperation among health institutions, health workers, NGOs, and political leaders. The case finding rate is now 69%, and nearly 95% of diagnosed TB cases are being treated under DOTS. The treatment success rate of new smear-positive cases is nearly 90%. Thus, DOTS increases the case finding and treatment success. 3. Cambodia: HIV/TB and the health sector reform: Tan Eang Mao (National Center for Tuberculosis and Leprosy Control, Cambodia) Cambodia is one of the 23 high burden countries of tuberculosis in the world. Moreover, HIV/AIDS has been spreading rapidly since 1990s, which is worsening the tuberculosis epidemics. To cope with the burden, Cambodia has started implementation of DOTS in 1994 and has expanded it to most of public hospitals across the country by 1998. NTP of Cambodia is now enjoying high cure rate of more than 90%. However, due to the constraints such as weak infrastructure and the poverty, it is proved that many of TB sufferers do not have access to the TB services, resulting in still low case detection rate. It is for this reason that the NTP has decided to expand DOTS to

  2. The outcome of tuberculosis treatment at a rural hospital in southern Ethiopia.

    PubMed

    Lindtjørn, B; Madebo, T

    2001-07-01

    We evaluated the treatment results of 239 patients with sputum positive pulmonary tuberculosis (TB) and describe potential factors associated with reduced programme performance in aTB treatment programme in Ethiopia.The TB registry was incomplete and 64 (26.8%) patients were not recorded in the control programme. Of the 239 patients, 34.3% received short-course chemotherapy (SCC) as a first treatment, 5.9% received SCC having previously been treated with standard long-course chemotherapy (LCC), and 54.4% were initially put on LCC. After excluding the 75 patients (31.4%) who were transferred to other health institutions outside the control area, 100 (61.0%; 95% CI 53.0-68.4) were cured (22.6%) or completed the treatment (38.4%) falling short of the target of 85%. Five months or later during treatment 1.8% remained smear-positive, 7.3% died and 29.9% interrupted their treatment. Sputum tests were done in 78% of the eligible patients at 2 months, in 20% at 5 months and in 60.2% at the expected time of treatment completion. By July 1998, 5.4% of the patients initially on LCC had relapsed and were retreated with SCC. None of those initially cured with SCC needed to be retreated. Compared with patients in theTB registry, non-registered patients had lower treatment completed and cure rates (42.3% versus 65.2%; P = 0.047), more patients were transferred out of the TB programme (59.4% versus 21.1%; P<0.001) and the defaulter rate was higher (57.7% versus 24.6%; P=0.002). Weaknesses in the programme performance include organizational issues such as the under use of theTB registry, deficient follow-up procedures, the common usage of LCC and unsatisfactory rates of defaulting.

  3. Epidemiology and Treatment of Multidrug Resistant Tuberculosis

    PubMed Central

    Mitnick, Carole D.; Appleton, Sasha C.; Shin, Sonya S.

    2010-01-01

    Multidrug resistant tuberculosis is now thought to afflict between 1 and 2 million patients annually. Although significant regional variability in the distribution of disease has been recorded, surveillance data are limited by several factors. The true burden of disease is likely underestimated. Nevertheless, the estimated burden is substantial enough to warrant concerted action. A range of approaches is possible, but all appropriate interventions require scale-up of laboratories and early treatment with regimens containing a sufficient number of second-line drugs. Ambulatory treatment for most patients, and improved infection control, can facilitate scale-up with decreased risk of nosocomial transmission. Several obstacles have been considered to preclude worldwide scale-up of treatment, mostly attributable to inadequate human, drug, and financial resources. Further delays in scale-up, however, risk continued generation and transmission of resistant tuberculosis, as well as associated morbidity and mortality. PMID:18810684

  4. Interventions to reduce tuberculosis mortality and transmission in low- and middle-income countries.

    PubMed Central

    Borgdorff, Martien W.; Floyd, Katherine; Broekmans, Jaap F.

    2002-01-01

    Tuberculosis is among the top ten causes of global mortality and affects low-income countries in particular. This paper examines, through a literature review, the impact of tuberculosis control measures on tuberculosis mortality and transmission, and constraints to scaling-up. It also provides estimates of the effectiveness of various interventions using a model proposed by Styblo. It concludes that treatment of smear-positive tuberculosis using the WHO directly observed treatment, short-course (DOTS) strategy has by far the highest impact. While BCG immunization reduces childhood tuberculosis mortality, its impact on tuberculosis transmission is probably minimal. Under specific conditions, an additional impact on mortality and transmission can be expected through treatment of smear-negative cases, intensification of case-finding for smear-positive tuberculosis, and preventive therapy among individuals with dual tuberculosis-HIV infection. Of these interventions, DOTS is the most cost-effective at around US$ 5-40 per disability-adjusted life year (DALY) gained. The cost for BCG immunization is likely to be under US$ 50 per DALY gained. Treatment of smear-negative patients has a cost per DALY gained of up to US$ 100 in low-income countries, and up to US$ 400 in middle-income settings. Other interventions, such as preventive therapy for HIV-positive individuals, appear to be less cost-effective. The major constraint to scaling up DOTS is lack of political commitment, resulting in shortages of funding and human resources for tuberculosis control. However, in recent years there have been encouraging signs of increasing political commitment. Other constraints are related to involvement of the private sector, health sector reform, management capacity of tuberculosis programmes, treatment delivery, and drug supply. Global tuberculosis control could benefit strongly from technical innovation, including the development of a vaccine giving good protection against smear-positive

  5. Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis Treatment

    PubMed Central

    Casals, M.; Caminero, J. A.; García-García, J. M.; Jiménez-Fuentes, M. A.; Medina, J. F.; Millet, J. P.; Ruiz-Manzano, J.; Caylá, J.

    2016-01-01

    Objective To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. Methods TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8–283.4); being retired (HR = 2.4;CI:1.1–5.1); having visited the emergency department (HR = 3.1;CI:1.2–7.7); HIV infection (HR = 3.4;CI:1.6–7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2–3.3) or non-standard treatments (HR = 2.68;CI:1.36–5.25); comprehension difficulties (HR = 2.8;CI:1.3–6.1); and smear-positive sputum (HR = 2.3-CI:1.0–4.8). Conclusion There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs. PMID:27487189

  6. [Tuberculosis annual report 2012--(4) Tuberculosis treatment and outcomes].

    PubMed

    2014-12-01

    Re-treatment frequency among patients newly diagnosed with tuberculosis (TB) might indicate inadequate prior treatment. Of 21,283 patients diagnosed with TB in 2012, 1,336 had received prior TB treatment. Among patients requiring re-treatment, more than half (n = 749) had received treatment after 2000. The initial recommended TB treatment regimen in Japan consisted of a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol or streptomycin. This regimen was used to treat approximately 90% of patients aged 15-49 years with all forms of TB. However, the proportion of patients substantially declined among patients ≥ 80 years of age. Of 13,650 patients who started a pyrazinamide TB treatment regimen in 2011, approximately 10% were unable to complete the 2-month-long pyrazinamide regimen by the end of 2012. In 2012, 16,432 patients were newly diagnosed with pulmonary TB (PTB). The proportion of patients hospitalized at the beginning of TB treatment increased among those ≥ 30 years of age. The median hospitalization duration among newly diagnosed patients with all forms of TB in 2011 was 64 days. The durations for those who had a new positive sputum smear result, were undergoing re-treatment, had a positive sputum result in other bacteriological tests, and had bacteriologically negative sputum PTB were 70, 72, 44, and 39 days, respectively. The median hospitalization duration was 43 days among patients with extrapulmonary TB. At the end of 2012, the median treatment duration in patients diagnosed in 2011 with all forms of TB was 273 days. The treatment success rates for patients who had a new positive sputum smear result (n = 7,736), were undergoing re-treatment (n = 747), had a positive sputum result in other bacteriological tests (n = 6,049), and had a bacteriologically negative sputum result (including other PTB patients) (n = 2,917) registered in 2011 were 50.6%, 41.2%, 58.0%, and 62.5%, respectively. The rate of loss to follow-up among patients who

  7. Rapid Whole-Genome Sequencing of Mycobacterium tuberculosis Isolates Directly from Clinical Samples

    PubMed Central

    Brown, Amanda C.; Einer-Jensen, Katja; Holdstock, Jolyon; Houniet, Darren T.; Chan, Jacqueline Z. M.; Depledge, Daniel P.; Nikolayevskyy, Vladyslav; Broda, Agnieszka; Stone, Madeline J.; Christiansen, Mette T.; Williams, Rachel; McAndrew, Michael B.; Tutill, Helena; Brown, Julianne; Melzer, Mark; Rosmarin, Caryn; McHugh, Timothy D.; Shorten, Robert J.; Drobniewski, Francis; Speight, Graham; Breuer, Judith

    2015-01-01

    The rapid identification of antimicrobial resistance is essential for effective treatment of highly resistant Mycobacterium tuberculosis. Whole-genome sequencing provides comprehensive data on resistance mutations and strain typing for monitoring transmission, but unlike for conventional molecular tests, this has previously been achievable only from cultures of M. tuberculosis. Here we describe a method utilizing biotinylated RNA baits designed specifically for M. tuberculosis DNA to capture full M. tuberculosis genomes directly from infected sputum samples, allowing whole-genome sequencing without the requirement of culture. This was carried out on 24 smear-positive sputum samples, collected from the United Kingdom and Lithuania where a matched culture sample was available, and 2 samples that had failed to grow in culture. M. tuberculosis sequencing data were obtained directly from all 24 smear-positive culture-positive sputa, of which 20 were of high quality (>20× depth and >90% of the genome covered). Results were compared with those of conventional molecular and culture-based methods, and high levels of concordance between phenotypical resistance and predicted resistance based on genotype were observed. High-quality sequence data were obtained from one smear-positive culture-negative case. This study demonstrated for the first time the successful and accurate sequencing of M. tuberculosis genomes directly from uncultured sputa. Identification of known resistance mutations within a week of sample receipt offers the prospect for personalized rather than empirical treatment of drug-resistant tuberculosis, including the use of antimicrobial-sparing regimens, leading to improved outcomes. PMID:25972414

  8. Prevalence of extended treatment in pulmonary tuberculosis patients receiving first-line therapy and its association with recurrent tuberculosis in Beijing, China

    PubMed Central

    Xia, YinYin; Goel, Sonu; Harries, Anthony D.; Zhang, ZhiGuo; Gao, TieJie; Wang, LiXia; Cheng, ShiMing; Lin, Yan; Du, Xin

    2014-01-01

    Background In China, it is known that extended treatment is given to patients with pulmonary TB after they have successfully completed 6 months of first-line treatment. This practice is not officially reported to the National Tuberculosis Control Programme, so there are no data on its prevalence, its possible benefits in terms of preventing recurrent disease or the costs. This study aimed to provide information, from a single TB dispensary in Beijing, China, on the prevalence of extended anti-TB treatment and its relationship with recurrent TB. Methods Retrospective cohort study using the electronic national TB information system and dispensary medical records. Results Of 935 patients with pulmonary TB who completed 6–7 months of first-line drug treatment, 399 (43%) were given extended treatment. This was more common in patients with smear-positive disease, and those with lung cavities and more extensive radiographic lobar involvement at the time of diagnosis. Over 3–4 years' follow-up, recurrent disease was not significantly different in patients who received extended treatment (2.8%, 11/399) as compared to those who received the standard 6-month treatment (3.7%, 20/534). The median length of extended treatment was 89 days at a median cost of US$111 for drugs and US$32 for laboratory examinations. Conclusions This study shows that extended treatment is common in one TB dispensary in Beijing. Further studies are needed to determine the countrywide prevalence of this practice and ascertain more conclusively the apparent lack of benefit. PMID:24864048

  9. Clinical Evaluation of Tuberculosis Viability Microscopy for Assessing Treatment Response

    PubMed Central

    Datta, Sumona; Sherman, Jonathan M.; Bravard, Marjory A.; Valencia, Teresa; Gilman, Robert H.; Evans, Carlton A.

    2015-01-01

    Background. It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. Methods. To assess treatment response, sputum samples (n = 124) from unselected patients (n = 35) with sputum microscopy–positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Results. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS = 0.85; P < .0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P < .001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P = .4) or quantitative culture (P = .6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P < .001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P = .6). Conclusions. Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy

  10. Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis.

    PubMed Central

    Bothamley, G H; Rudd, R; Festenstein, F; Ivanyi, J

    1992-01-01

    BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis. PMID:1585290

  11. To control and beyond: moving towards eliminating the global tuberculosis threat

    PubMed Central

    Brewer, T.; Heymann, S

    2004-01-01

    For 10 years the World Health Organisation has had a single answer to the deadly threat of tuberculosis (TB)—provide treatment to smear positive patients and watch them take it. In contrast with confident statements about how global TB would be brought under control when directly observed therapy, short course (DOTS) was introduced, TB continues to rise worldwide. The introduction of selected multiple drug resistant TB treatment programmes, "DOTS-Plus", although important, also focuses on therapy for active TB. HIV endemic countries in particular have experienced tremendous increases in TB despite having DOTS programmes. A critical review of recent epidemiological data and computer models shows that the present international strategy of concentrating on providing treatment for smear positive TB, DOTS and DOTS-Plus, is likely to have only a modest impact on population based TB control. Effective global TB control will require strategies that go beyond relying on treatment of people with active disease. PMID:15365106

  12. Childhood Tuberculosis in a Sub-Saharan Tertiary Facility: Epidemiology and Factors Associated with Treatment Outcome.

    PubMed

    Aketi, Loukia; Kashongwe, Zacharie; Kinsiona, Christian; Fueza, Serge Bisuta; Kokolomami, Jack; Bolie, Grace; Lumbala, Paul; Diayisu, Joseph Shiku

    2016-01-01

    Childhood tuberculosis (TB) is a diagnostic challenge in developing countries, and patient outcome can be influenced by certain factors. We report the disease course, clinical profile and factors associated with treatment outcome in a tertiary facility of Kinshasa. Documentary and analytical studies were conducted using clinical and exploratory data for children aged up to 15 years who were admitted to the University Clinics of Kinshasa for TB. Data are presented as frequencies and averages, and binary and logistic regression analyses were performed. Of 283 children with TB, 82 (29.0%) had smear-negative TB, 40 (14.1%) had smear-positive TB, 159 (56.1%) had extra-pulmonary TB (EPTB), 2 (0.7%) had multidrug-resistant TB (MDR-TB), 167 (59.0%) completed treatment, 30 (10.6%) were cured, 7 (2.5%) failed treatment, 4 (1.4%) died, 55 (19.4%) were transferred to health centers nearest their home, and 20 (7.0%) were defaulters. In the binary analysis, reported TB contacts (p = 0.048), type of TB (p = 0.000), HIV status (p = 0.050), Ziehl-Nielsen test result (p = 0.000), Lowenstein culture (p = 0.004) and chest X-ray (p = 0.057) were associated with outcome. In the logistic regression, none of these factors was a significant predictor of outcome. Tertiary level care facilities must improve the diagnosis and care of patients with childhood TB, which justifies the development of alternative diagnostic techniques and the assessment of other factors that potentially affect outcome. PMID:27101146

  13. Childhood Tuberculosis in a Sub-Saharan Tertiary Facility: Epidemiology and Factors Associated with Treatment Outcome

    PubMed Central

    Kinsiona, Christian; Fueza, Serge Bisuta; Kokolomami, Jack; Bolie, Grace; Lumbala, Paul

    2016-01-01

    Childhood tuberculosis (TB) is a diagnostic challenge in developing countries, and patient outcome can be influenced by certain factors. We report the disease course, clinical profile and factors associated with treatment outcome in a tertiary facility of Kinshasa. Documentary and analytical studies were conducted using clinical and exploratory data for children aged up to 15 years who were admitted to the University Clinics of Kinshasa for TB. Data are presented as frequencies and averages, and binary and logistic regression analyses were performed. Of 283 children with TB, 82 (29.0%) had smear-negative TB, 40 (14.1%) had smear-positive TB, 159 (56.1%) had extra-pulmonary TB (EPTB), 2 (0.7%) had multidrug-resistant TB (MDR-TB), 167 (59.0%) completed treatment, 30 (10.6%) were cured, 7 (2.5%) failed treatment, 4 (1.4%) died, 55 (19.4%) were transferred to health centers nearest their home, and 20 (7.0%) were defaulters. In the binary analysis, reported TB contacts (p = 0.048), type of TB (p = 0.000), HIV status (p = 0.050), Ziehl-Nielsen test result (p = 0.000), Lowenstein culture (p = 0.004) and chest X-ray (p = 0.057) were associated with outcome. In the logistic regression, none of these factors was a significant predictor of outcome. Tertiary level care facilities must improve the diagnosis and care of patients with childhood TB, which justifies the development of alternative diagnostic techniques and the assessment of other factors that potentially affect outcome. PMID:27101146

  14. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis

    PubMed Central

    Conde, Marcus B.; Mello, Fernanda C. Q.; Duarte, Rafael Silva; Cavalcante, Solange C.; Rolla, Valeria; Dalcolmo, Margareth; Loredo, Carla; Durovni, Betina; Armstrong, Derek T.; Efron, Anne; Barnes, Grace L.; Marzinke, Mark A.; Savic, Radojka M.; Dooley, Kelly E.; Cohn, Silvia; Moulton, Lawrence H.; Chaisson, Richard E.; Dorman, Susan E.

    2016-01-01

    Background The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment. Methods Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment. Results 121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450–600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were

  15. Diagnosis and Treatment of Extrapulmonary Tuberculosis

    PubMed Central

    2015-01-01

    Extrapulmonary tuberculosis (EPTB) constitutes about 20% of all cases of tuberculosis (TB) in Korea. Diagnosing EPTB remains challenging because clinical samples obtained from relatively inaccessible sites may be paucibacillary, thus decreasing the sensitivity of diagnostic tests. Whenever practical, every effort should be made to obtain appropriate specimens for both mycobacteriologic and histopathologic examinations. The measurement of biochemical markers in TB-affected serosal fluids (adenosine deaminase or gamma interferon) and molecular biology techniques such as polymerase chain reaction may be useful adjuncts in the diagnosis of EPTB. Although the disease usually responds to standard anti-TB drug therapy, the ideal regimen and duration of treatment have not yet been established. A paradoxical response frequently occurs during anti-TB therapy. It should be distinguished from other causes of clinical deterioration. Surgery is required mainly to obtain valid diagnostic specimens and to manage complications. Because smear microscopy or culture is not available to monitor patients with EPTB, clinical monitoring is the usual way to assess the response to treatment. PMID:25861336

  16. [The role of pharmacogenomics in the tuberculosis treatment regime].

    PubMed

    Guio, Heinner; Levano, Kelly S; Sánchez, Cesar; Tarazona, David

    2015-10-01

    Tuberculosis is a health problem worldwide with one-third of the population infected with the Mycobacterium tuberculosis bacilli. The first-line of treatment for tuberculosis includes the drugs Isoniazid (INH) and Rifampicin (RIF) metabolized in the liver. Drug metabolism is directly related to the genetic variation of NAT2 and CYP2E1 (associated with INH metabolism) and AADAC (associated with RIF metabolism), and the effects produced in an individual may be a fast, intermediate or slow metobolizer. Polymorphisms in genes of people in standard tuberculosis treatment can cause effects on drug metabolism with consequences of hepatotoxicity and even drug resistance. Countries have began clinical trials focused on personalization of tuberculosis treatment to reduce the consequences for patients in treatment. In countries like Peru, where high rates of tuberculosis are recorded and therefore more people in treatment, the pharmacogenomic of individuals becomes a crucial tool for an optimum tuberculosis treatment. This review highlights the importance of having pharmacogenomic studies and having the identification of polymorphisms associated to the metabolism of the anti-tuberculosis drugs in our Peruvian population. PMID:26732931

  17. [Progress report on a World Bank loan to China for a tuberculosis control project].

    PubMed

    Zhao, F; Chi, Y; Wang, K

    1995-02-01

    The progress of the World Bank loaned TB control project implemented from the second quarter of 1991 to the fourth quarter of 1993 was described in this paper. In the past three years, 737 counties of the 12 provinces with the population of 360 million has been covered by the project. Among 95176 new smear positive cases discovered, 93909 patients received free treatment of TB. The treatment coverage is 98.7%, of which 95% were treated under full course supervision. The smear conversion rate at two, three months of new smear positive TB patients are 83.4% and 90.6% respectively. The cohort analysis showed that the cure rate is 89.8%, which has reached the advanced level of the modern national tuberculosis control programme in the world.

  18. Saudi guidelines for testing and treatment of latent tuberculosis infection

    PubMed Central

    Al Jahdali, Hamdan H.; Baharoon, Salim; Abba, Abdullah A.; Memish, Ziad A.; Alrajhi, Abdulrahman A.; AlBarrak, Ali; Haddad, Qais A.; Al Hajjaj, Mohammad; Pai, Madhukar; Menzies, Dick

    2010-01-01

    Pulmonary tuberculosis is a common disease in Saudi Arabia. As most cases of tuberculosis are due to reactivation of latent infection, identification of individuals with latent tuberculosis infection (LTBI) who are at increased risk of progression to active disease, is a key element of tuberculosis control programs. Whereas general screening of individuals for LTBI is not cost-effective, targeted testing of individuals at high risk of disease progression is the right approach. Treatment of those patients with LTBI can diminish the risk of progression to active tuberculosis disease in the majority of treated patients. This statement is the first Saudi guideline for testing and treatment of LTBI and is a result of the cooperative efforts of four local Saudi scientific societies. This Guideline is intended to provide physicians and allied health workers in Saudi Arabia with the standard of care for testing and treatment of LTBI. PMID:20103957

  19. Adherence to Tuberculosis Treatment, Sputum Smear Conversion and Mortality: A Retrospective Cohort Study in 48 Rwandan Clinics

    PubMed Central

    Kayigamba, Felix R.; Bakker, Mirjam I.; Mugisha, Veronicah; De Naeyer, Ludwig; Gasana, Michel; Cobelens, Frank; van der Loeff, Maarten Schim

    2013-01-01

    Background Adherence to treatment and sputum smear conversion after 2 months of treatment are thought to be important for successful outcome of tuberculosis (TB) treatment. Methods Retrospective cohort study of new adult TB patients diagnosed in the first quarter of 2007 at 48 clinics in Rwanda. Data were abstracted from TB registers and individual treatment charts. Logistic regression analysis was done to examine associations between baseline demographic and clinical factors and three outcomes adherence, sputum smear conversion at two months, and death. Results Out of 725 eligible patients the treatment chart was retrieved for 581 (80%). Fifty-six (10%) of these patients took <90% of doses (defined as poor adherence). Baseline demographic characteristics were not associated with adherence to TB treatment, but adherence was lower among HIV patients not taking antiretroviral therapy (ART); p = 0.03). Sputum smear results around 2 months after start of treatment were available for 220 of 311 initially sputum-smear-positive pulmonary TB (PTB+) patients (71%); 175 (80%) had achieved sputum smear conversion. In multivariable analysis, baseline sputum smear grade (odds ratio [OR] = 2.7, 95% Confidence interval [CI] 1.1–6.6 comparing smear 3+ against 1+) and HIV infection (OR 3.0, 95%CI 1.3–6.7) were independent predictors for non-conversion at 2 months. Sixty-nine of 574 patients (12%) with known TB treatment outcomes had died. Besides other known determinants, poor adherence had an independent, strong effect on mortality (OR 3.4, 95%CI 1.4–7.8). Conclusion HIV infection is an important independent predictor of failure of sputum smear conversion at 2 months among PTB+ patients. Poor adherence to TB treatment is an important independent determinant of mortality. PMID:24066053

  20. Pulmonary langerhans cell histiocytosis masquerading as tuberculosis in an infant.

    PubMed

    Senanayake, M P; Mettananda, S; De Silva, M V C

    2011-01-01

    A 4-month-old infant presented with continued fever, unresolving bronchopneumonia and household contact with sputum-smear-positive tuberculosis (TB) and showed marginal improvement on anti-TB chemotherapy. Recurrent pneumothorax prompted the clinical diagnosis of TB to be revised. High-resolution CT scan of the chest and open lung biopsy confirmed the diagnosis of pulmonary Langerhans cell histiocytosis. Treatment with prednisolone and vinblastin resulted in settling of fever and resolution of respiratory symptoms and signs. In communities where the prevalence of TB is high, unusual presentations should prompt consideration of alternative diagnoses. PMID:22041471

  1. Chest Radiographic Patterns and the Transmission of Tuberculosis: Implications for Automated Systems

    PubMed Central

    Lau, Angela; Barrie, James; Winter, Christopher; Elamy, Abdel-Halim; Tyrrell, Gregory; Long, Richard

    2016-01-01

    Background Computer-aided detection to identify and diagnose pulmonary tuberculosis is being explored. While both cavitation on chest radiograph and smear-positivity on microscopy are independent risk factors for the infectiousness of pulmonary tuberculosis it is unknown which radiographic pattern, were it detectable, would provide the greatest public health benefit; i.e. reduced transmission. Herein we provide that evidence. Objectives 1) to determine whether pulmonary tuberculosis in a high income, low incidence country is more likely to present with “typical” adult-type pulmonary tuberculosis radiographic features and 2) to determine whether those with “typical” radiographic features are more likely than those without such features to transmit the organism and/or cause secondary cases. Methods Over a three-year period beginning January 1, 2006 consecutive adults with smear-positive pulmonary tuberculosis in the Province of Alberta, Canada, were identified and their pre-treatment radiographs scored by three independent readers as “typical” (having an upper lung zone predominant infiltrate, with or without cavitation but no discernable adenopathy) or “atypical” (all others). Each patient’s pre-treatment bacillary burden was carefully documented and, during a 30-month transmission window, each patient’s transmission events were recorded. Mycobacteriology, radiology and transmission were compared in those with “typical” versus “atypical” radiographs. Findings A total of 97 smear-positive pulmonary tuberculosis cases were identified, 69 (71.1%) with and 28 (28.9%) without “typical” chest radiographs. “Typical” cases were more likely to have high bacillary burdens and cavitation (Odds Ratios and 95% Confidence Intervals: 2.75 [1.04–7.31] and 9.10 [2.51–32.94], respectively). Typical cases were also responsible for most transmission events—78% of tuberculin skin test conversions (p<0.002) and 95% of secondary cases in reported

  2. Cutaneous tuberculosis: diagnosis, histopathology and treatment - Part II*

    PubMed Central

    dos Santos, Josemir Belo; Figueiredo, Ana Roberta; Ferraz, Cláudia Elise; de Oliveira, Márcia Helena; da Silva, Perla Gomes; de Medeiros, Vanessa Lucília Sileira

    2014-01-01

    The evolution in the knowledge of tuberculosis' physiopathology allowed not only a better understanding of the immunological factors involved in the disease process, but also the development of new laboratory tests, as well as the establishment of a histological classification that reflects the host's ability to contain the infectious agent. At the same time, the increasing bacilli resistance led to alterations in the basic tuberculosis treatment scheme in 2009. This article critically examines laboratory and histological investigations, treatment regimens for tuberculosis and possible adverse reactions to the most frequently used drugs. PMID:25054739

  3. Patient Characteristics Associated with Tuberculosis Treatment Default: A Cohort Study in a High-Incidence Area of Lima, Peru

    PubMed Central

    Lackey, Brian; Seas, Carlos; Van der Stuyft, Patrick; Otero, Larissa

    2015-01-01

    Background Although tuberculosis (TB) is usually curable with antibiotics, poor adherence to medication can lead to increased transmission, drug resistance, and death. Prior research has shown several factors to be associated with poor adherence, but this problem remains a substantial barrier to global TB control. We studied patients in a high-incidence district of Lima, Peru to identify factors associated with premature termination of treatment (treatment default). Methods We conducted a prospective cohort study of adult smear-positive TB patients enrolled between January 2010 and December 2011 with no history of TB disease. Descriptive statistics and multivariable logistic regression analyses were performed to determine risk factors associated with treatment default. Results Of the 1233 patients studied, 127 (10%) defaulted from treatment. Patients who defaulted were more likely to have used illegal drugs (OR = 4.78, 95% CI: 3.05-7.49), have multidrug-resistant TB (OR = 3.04, 95% CI: 1.58-5.85), not have been tested for HIV (OR = 2.30, 95% CI: 1.50-3.54), drink alcohol at least weekly (OR = 2.22, 95% CI: 1.40-3.52), be underweight (OR = 2.08, 95% CI: 1.21-3.56), or not have completed secondary education (OR = 1.55, 95% CI: 1.03-2.33). Conclusions Our study identified several factors associated with defaulting from treatment, suggesting a complex set of causes that might lead to default. Addressing these factors individually would be difficult, but they might help to identify certain high-risk patients for supplemental intervention prior to treatment interruption. Treatment adherence remains a barrier to successful TB care and reducing the frequency of default is important for both the patients’ health and the health of the community. PMID:26046766

  4. Ethical issues in tuberculosis diagnosis and treatment.

    PubMed

    Selgelid, M J; Reichman, L B

    2011-06-01

    Drug-resistant tuberculosis (TB) has highlighted the need for discussion of ethical questions about TB diagnosis and treatment. Drug resistance is a human-made phenomenon. It is caused by lack of patient adherence in drug taking and/or physician failure in prescription making. The global burden of TB is also partly explained by the lack of industry motivation to develop new TB drugs and diagnostics. This article explores the primary ethical issues associated with TB diagnosis and treatment: the human rights requirements regarding universal access to care and universal standards of care, treatment exclusion and cessation, privacy and stigmatisation in the context of directly observed therapy, and diagnostic challenges posed by limited laboratory capacity. Inter alia, it argues that: 1) the ethical imperative to improve individual patient care is partly based on the need to prevent the spread of infection and the exacerbation of the problem of drug resistance; 2) human rights and the imperative to protect the greater good of public health may call for increased regulation of the private sector; and 3) industry should be given further incentives to develop new tools for TB control.

  5. [Hospital detention in tuberculosis control].

    PubMed

    Villalbí, Joan R; Rodríguez-Campos, Mònica; Orcau, Àngels; Espachs, M Àngels; Salamero, Marta; Maldonado, José; Caylà, Joan A

    2016-01-01

    This article describes the actions of public health services of the city of Barcelona to prevent tuberculosis transmission by noncompliant smear-positive patients by using the possibilities of Spanish Law 3/1986. The actions were based on a resolution of the health authorities on the need to locate such patients and to detain them in hospitals to provide treatment. This involved police cooperation, informing noncompliant patients, and requesting ratification from the Administrative Court. The article describes the process and the characteristics of the cases involved. Over nine years, from July 2006 to June 2015, the law was used in only twelve cases. The authors conclude that the criteria of prudence and proportionality were used in the application of the law, which resulted in the treatment of patients who posed a risk to their environment, reducing the transmission of infection. PMID:26832855

  6. [Hospital detention in tuberculosis control].

    PubMed

    Villalbí, Joan R; Rodríguez-Campos, Mònica; Orcau, Àngels; Espachs, M Àngels; Salamero, Marta; Maldonado, José; Caylà, Joan A

    2016-01-01

    This article describes the actions of public health services of the city of Barcelona to prevent tuberculosis transmission by noncompliant smear-positive patients by using the possibilities of Spanish Law 3/1986. The actions were based on a resolution of the health authorities on the need to locate such patients and to detain them in hospitals to provide treatment. This involved police cooperation, informing noncompliant patients, and requesting ratification from the Administrative Court. The article describes the process and the characteristics of the cases involved. Over nine years, from July 2006 to June 2015, the law was used in only twelve cases. The authors conclude that the criteria of prudence and proportionality were used in the application of the law, which resulted in the treatment of patients who posed a risk to their environment, reducing the transmission of infection.

  7. Smoking increases the risk of relapse after successful tuberculosis treatment

    PubMed Central

    d’Arc Lyra Batista, Joanna; de Fátima Pessoa Militão de Albuquerque, Maria; de Alencar Ximenes, Ricardo Arraes; Rodrigues, Laura Cunha

    2008-01-01

    Background Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking. Methods A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001–2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up. Results Smoking (OR 2.53, 95% CI 1.23–5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46–8.93) were found to be independently associated with relapse of tuberculosis. Conclusions Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. PMID:18556729

  8. Reciprocity and Ethical Tuberculosis Treatment and Control.

    PubMed

    Silva, Diego S; Dawson, Angus; Upshur, Ross E G

    2016-03-01

    This paper explores the notion of reciprocity in the context of active pulmonary and laryngeal tuberculosis (TB) treatment and related control policies and practices. We seek to do three things: First, we sketch the background to contemporary global TB care and suggest that poverty is a key feature when considering the treatment of TB patients. We use two examples from TB care to explore the role of reciprocity: isolation and the use of novel TB drugs. Second, we explore alternative means of justifying the use of reciprocity through appeal to different moral and political theoretical traditions (i.e., virtue ethics, deontology, and consequentialism). We suggest that each theory can be used to provide reasons to take reciprocity seriously as an independent moral concept, despite any other differences. Third, we explore general meanings and uses of the concept of reciprocity, with the primary intention of demonstrating that it cannot be simply reduced to other more frequently invoked moral concepts such as beneficence or justice. We argue that reciprocity can function as a mid-level principle in public health, and generally, captures a core social obligation arising once an individual or group is burdened as a result of acting for the benefit of others (even if they derive a benefit themselves). We conclude that while more needs to be explored in relation to the theoretical justification and application of reciprocity, sufficient arguments can be made for it to be taken more seriously as a key principle within public health ethics and bioethics more generally. PMID:26797512

  9. Reciprocity and Ethical Tuberculosis Treatment and Control.

    PubMed

    Silva, Diego S; Dawson, Angus; Upshur, Ross E G

    2016-03-01

    This paper explores the notion of reciprocity in the context of active pulmonary and laryngeal tuberculosis (TB) treatment and related control policies and practices. We seek to do three things: First, we sketch the background to contemporary global TB care and suggest that poverty is a key feature when considering the treatment of TB patients. We use two examples from TB care to explore the role of reciprocity: isolation and the use of novel TB drugs. Second, we explore alternative means of justifying the use of reciprocity through appeal to different moral and political theoretical traditions (i.e., virtue ethics, deontology, and consequentialism). We suggest that each theory can be used to provide reasons to take reciprocity seriously as an independent moral concept, despite any other differences. Third, we explore general meanings and uses of the concept of reciprocity, with the primary intention of demonstrating that it cannot be simply reduced to other more frequently invoked moral concepts such as beneficence or justice. We argue that reciprocity can function as a mid-level principle in public health, and generally, captures a core social obligation arising once an individual or group is burdened as a result of acting for the benefit of others (even if they derive a benefit themselves). We conclude that while more needs to be explored in relation to the theoretical justification and application of reciprocity, sufficient arguments can be made for it to be taken more seriously as a key principle within public health ethics and bioethics more generally.

  10. [Tuberculosis: actual problems with diagnosis and treatment].

    PubMed

    Korzeniewska-Koseła, Maria

    2016-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex. It remains health problem also in developed countries. Most common form of tuberculosis is pulmonary disease but other sites of the body can be affected (extrapulmonary TB). As TB incidence falls, the probability of developing active diseases in people infected with M. tuberculosis is higher among imunocompromised people and in people from risk groups. People who present with unexplained cough lasting two or more weeks or with findings suggestive of tuberculosis on chest radiographs should be evaluated for tuberculosis. For patients suspected of having pulmonary or extrapulmonary tuberculosis specimens from the sites of involvement should be obtained for microbiological tests. Bronchoscopy and BAL should be performed in patients that do not produce sputum and with negative sputum smears. Ct scan may also play an important role in the evaluation of patients suspected of having TB but with negative sputum smears. The standard therapy for TB should consist of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol in the initial phase and of isoniazid and rifampicin given for 4 months (the continuation phase). PMID:27421129

  11. Diagnosis and Treatment of Latent Tuberculosis Infection in Healthcare Workers

    PubMed Central

    2016-01-01

    Tuberculosis (TB) is one of the most important occupational risks for healthcare workers (HCWs) in South Korea. Many policies regarding the control and prevention of TB in healthcare settings recommend that HCWs are tested for latent tuberculosis infection (LTBI) in addition to active TB. Moreover, the Korean Tuberculosis Prevention Act also recommends that HCWs receive regular testing for LTBI. However, there are no specific or detailed guidelines for dealing with LTBI in HCWs. Herein, we discuss the diagnosis and treatment of LTBI in HCWs and focus particularly on the baseline screening of hired HCWs, routine follow-up, and contact investigation. PMID:27433172

  12. STUDY OF THE STATUS OF TUBERCULOSIS CONTROL PROGRAM BASED ON THE IMPLEMENTATION OF THE DIRECTLY OBSERVED TREATMENT SHORT-COURSE STRATEGY (DOTS)

    PubMed Central

    Farzianpour, Fereshteh; Kooshad, Mahdokht Afarin

    2016-01-01

    Introduction: Ascendant trend of tuberculosis in the world introduces this disease to be one of the most important infectious diseases in the world. So that every year, 9 million people are afflicted to active TB and about 5.1 million people die of the disease. As the HIV contaminated cases are increased, emergence and spread field of Multidrug-resistant tuberculosis (MDR-TB) bacilli has been provided. Objective: This study aimed to assess the Tuberculosis Control Program from 2005 to 2012 to determine the overall situation of disease epidemiology and prioritized strategies in disease control program within the south of Tehran. Materials and Methods: This cross-sectional study was extracted and analyzed retrospectively on the basis of records of all TB patients in TB health center and TB software in south Tehran in 2005-2012 years. Results: From the total population under protection of health center of south Tehran, 99% are urban and 1% are rural. During 2005-2012, 1242 TB cases have been registered and they were treated by DOTS method. There were 553 cases of new smear-positive pulmonary TB (44%), 222 cases of smear-negative pulmonary TB (18%) and 336 cases of extra-pulmonary tuberculosis (27%), 26 cases of recurrence (2%) and 11 cases of MDR (0.9%). Smear-positive pulmonary tuberculosis has included 67.4% of all tuberculosis patients. Conclusions: The results showed that, in accordance with TB worldwide statistics, at the health center of south Tehran, pulmonary TB is the most common form of the disease (67.4%). The incidence of smear-positive tuberculosis and all forms of TB cases has been an ascending trend over the period between 2005 and 2012. PMID:27698595

  13. STUDY OF THE STATUS OF TUBERCULOSIS CONTROL PROGRAM BASED ON THE IMPLEMENTATION OF THE DIRECTLY OBSERVED TREATMENT SHORT-COURSE STRATEGY (DOTS)

    PubMed Central

    Farzianpour, Fereshteh; Kooshad, Mahdokht Afarin

    2016-01-01

    Introduction: Ascendant trend of tuberculosis in the world introduces this disease to be one of the most important infectious diseases in the world. So that every year, 9 million people are afflicted to active TB and about 5.1 million people die of the disease. As the HIV contaminated cases are increased, emergence and spread field of Multidrug-resistant tuberculosis (MDR-TB) bacilli has been provided. Objective: This study aimed to assess the Tuberculosis Control Program from 2005 to 2012 to determine the overall situation of disease epidemiology and prioritized strategies in disease control program within the south of Tehran. Materials and Methods: This cross-sectional study was extracted and analyzed retrospectively on the basis of records of all TB patients in TB health center and TB software in south Tehran in 2005-2012 years. Results: From the total population under protection of health center of south Tehran, 99% are urban and 1% are rural. During 2005-2012, 1242 TB cases have been registered and they were treated by DOTS method. There were 553 cases of new smear-positive pulmonary TB (44%), 222 cases of smear-negative pulmonary TB (18%) and 336 cases of extra-pulmonary tuberculosis (27%), 26 cases of recurrence (2%) and 11 cases of MDR (0.9%). Smear-positive pulmonary tuberculosis has included 67.4% of all tuberculosis patients. Conclusions: The results showed that, in accordance with TB worldwide statistics, at the health center of south Tehran, pulmonary TB is the most common form of the disease (67.4%). The incidence of smear-positive tuberculosis and all forms of TB cases has been an ascending trend over the period between 2005 and 2012.

  14. Hematological and liver toxicity of anti-tuberculosis drugs

    PubMed Central

    Mirlohi, Maryam-Sadat; Ekrami, Alireza; Shirali, Saeed; Ghobeishavi, Mehdi; Pourmotahari, Fatemeh

    2016-01-01

    Introduction Tuberculosis (TB) is a major global health problem, and anti-tuberculosis drugs can cause severe adverse reactions. The aim of this study was to determine hematological and biochemical changes and associated risk factors in smear positive pulmonary tuberculosis patients undergoing treatment with standard protocols. Methods In a descriptive study, a total of 40 tuberculosis patients aged between 15–60 years were collected from hospitals in Khuzestan Province (Iran) from March 2013 to March 2014. The patients were treated with drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) during the initial two months, followed by isoniazid and rifampicin for the next four to six months. Activities of liver enzymes (ALT, AST, and ALP) and hematological parameters were recorded before and after treatment. Data were analyzed using paired samples t-test and Wilcoxon test by SPSS 16. Results After using drug treatments, hematological parameters (RBC, Hb, HCT, MCV, MCH, and MCHC), except platelet count, were changed significantly (p ≤ 0.001). Liver enzyme activities (ALT, AST, and ALP) were decreased significantly (p ≤ 0.001) after treatment. Conclusion In this study, changes of hematological and biochemical parameters have been observed in patients with pulmonary tuberculosis. It can be concluded that the anti-tuberculosis treatment is associated with changes of hematological parameters and liver enzymes. PMID:27790357

  15. Diagnosis and treatment of latent infection with Mycobacterium tuberculosis.

    PubMed

    Chee, Cynthia Bin-Eng; Sester, Martina; Zhang, Wenhong; Lange, Christoph

    2013-02-01

    In clinical practice, latent infection with Mycobacterium tuberculosis is defined by the presence of an M. tuberculosis-specific immune response in the absence of active tuberculosis. Targeted testing of individuals from risk groups with the tuberculin skin test or an interferon-γ release assay is currently the best method to identify those with the highest risk for progression to tuberculosis. Positive predictive values of the immunodiagnostic tests are substantially influenced by the type of test, the age of the person who is tested, the prevalence of tuberculosis in the society and the risk group to which the person belongs. As a general rule, testing should only be offered when preventive chemotherapy will be accepted in the case of a positive test result. Preventive chemotherapy can effectively protect individuals at risk from the development of tuberculosis, although at least 3 months of combination therapy or up to 9 months of monotherapy are required, and overall acceptance rate is low. Improvements of the current generation of immunodiagnostic tests could substantially lower the number of individuals that need to be treated to prevent a case of tuberculosis. If shorter treatment regimens were equally effective than those currently recommended, acceptance of preventive chemotherapy could be much improved.

  16. Impact of awareness drives and community-based active tuberculosis case finding in Odisha, India.

    PubMed

    Parija, D; Patra, T K; Kumar, A M V; Swain, B K; Satyanarayana, S; Sreenivas, A; Chadha, V K; Moonan, P K; Oeltmann, J E

    2014-09-01

    India's Revised National Tuberculosis Control programme employs passive case detection. The new sputum smear-positive case detection rate is less than 70% in Odisha State. During April-June 2012, active case finding (ACF) was conducted through awareness drives and field-based tuberculosis (TB) screening in select communities with the lowest case detection rates. During the campaign, 240 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 11% relative to April-June 2011 in intervention communities compared to an 0.8% increase in non-intervention communities. ACF brought TB services closer to the community and increased TB case detection.

  17. Rapid Improvement in Passive Tuberculosis Case Detection and Tuberculosis Treatment Outcomes After Implementation of a Bundled Laboratory Diagnostic and On-Site Training Intervention Targeting Mid-Level Providers

    PubMed Central

    Manabe, Yukari C.; Zawedde-Muyanja, Stella; Burnett, Sarah M.; Mugabe, Frank; Naikoba, Sarah; Coutinho, Alex

    2015-01-01

    Background. Tuberculosis (TB) control is a public health priority with 3 million cases unrecognized by the public health system each year. We assessed the impact of improved TB diagnostics and on-site training on TB case detection and treatment outcomes in rural healthcare facilities. Methods. Fluorescence microscopy, Xpert MTB/RIF, and on-site training were introduced at 10 healthcare facilities. Using quasi-experimental methods, these 10 intervention healthcare facilities were compared with 2 controls and their own performance the previous year. Results. From January to October 2012, 186 357 and 32 886 outpatients were seen in the 10 intervention and 2 control facilities, respectively. The intervention facilities had a 52.04% higher proportion of presumptive TB cases with a sputum examination (odds ratio [OR] = 12.65; 95% confidence interval [CI], 5.60–28.55). After adjusting for age group and gender, the proportion of smear-positive patients initiated on treatment was 37.76% higher in the intervention than in the control facilities (adjusted OR [AOR], 7.59; 95% CI, 2.19–26.33). After adjusting for the factors above, as well as human immunodeficiency virus and TB retreatment status, the proportion of TB cases who completed treatment was 29.16% higher (AOR, 4.89; 95% CI, 2.24–10.67) and the proportion of TB cases who were lost to follow-up was 66.98% lower (AOR, 0.04; 95% CI, 0.01–0.09). When compared with baseline performance, the intervention facilities had a significantly higher proportion of presumptive TB cases with a sputum examination (64.70% vs 3.44%; OR, 23.95; 95% CI, 12.96–44.25), and these facilities started 56.25% more smear-positive TB cases on treatment during the project period (AOR, 15.36; 95% CI, 6.57–35.91). Conclusions. Optimizing the existing healthcare workforce through a bundled diagnostics and on-site training intervention for nonphysician healthcare workers will rapidly improve TB case detection and outcomes towards

  18. Tuberculosis

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Tuberculosis KidsHealth > For Teens > Tuberculosis Print A A A Text Size What's in ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...

  19. Evaluation of the semiautomated Abbott LCx Mycobacterium tuberculosis assay for direct detection of Mycobacterium tuberculosis in respiratory specimens.

    PubMed Central

    Ausina, V; Gamboa, F; Gazapo, E; Manterola, J M; Lonca, J; Matas, L; Manzano, J R; Rodrigo, C; Cardona, P J; Padilla, E

    1997-01-01

    Five hundred twenty processed respiratory specimens from 326 patients received for the diagnosis of tuberculosis or other mycobacterial infections were tested by means of the LCx Mycobacterium tuberculosis Assay from Abbott Laboratories, which uses ligase chain reaction technology for the direct detection of M. tuberculosis complex in respiratory specimens. The results of the LCx M. tuberculosis Assay were compared with the results of culture and staining techniques. After a combination of culture results and the patient's clinical data, a total of 195 specimens were collected from 110 patients who were positively diagnosed as having pulmonary tuberculosis. Twenty-three of these 195 specimens which corresponded to 10 patients with a history of pulmonary tuberculosis (TB) and anti-TB treatment ranging from 1 to 6 months were culture negative. The other 172 specimens were culture positive for M. tuberculosis. With an overall positivity rate of 37.5% (195 of 520 specimens), the sensitivity, specificity, and positive and negative predictive values were 90.8, 100, 100, and 94.7%, respectively, for the LCx M. tuberculosis Assay; 88.2, 100, 100, and 93.4%, respectively, for culture; and 82.6, 92, 72.9, and 97.6%, respectively, for acid-fast staining. For 161 specimens (82.6%) from patients smear positive for the disease and 34 specimens (17.4%) from patients smear negative for the disease, the sensitivity values for the LCx M. tuberculosis Assay were 98.8 and 53%, respectively. There were no statistically significant differences in the sensitivities and specificities between the LCx M. tuberculosis Assay and culture (P > 0.05). Conclusively, the LCx M. tuberculosis Assay has proved to have an acceptable sensitivity and a high specificity in detecting M. tuberculosis and has the potential of reducing the diagnosis time to an 8-h working day. PMID:9230369

  20. Characteristics and Treatment Outcomes of Retreatment Tuberculosis Patients in Benin.

    PubMed

    Ade, Serge; Adjibodé, Omer; Wachinou, Prudence; Toundoh, Narcisse; Awanou, Bérénice; Agodokpessi, Gildas; Affolabi, Dissou; Adè, Gabriel; Harries, Anthony D; Anagonou, Séverin

    2016-01-01

    Objective. To determine among retreatment tuberculosis patients in Benin baseline characteristics, culture, and drug sensitivity testing (DST) results and treatment outcomes. Materials and Methods. A retrospective national cohort study of all retreatment tuberculosis patients in Benin in 2013 using registers and treatment cards. Results. Of 3957 patients with tuberculosis, 241 (6%) were retreatment cases. Compared to new pulmonary bacteriologically confirmed tuberculosis (NPBCT) patients, there were significantly higher numbers of males (P = 0.04), patients from "Atlantique-Littoral" (P = 0.006), patients aged 45-64 years (P = 0.007), and HIV-positive patients (P = 0.04) among those retreated. Overall, 171 (71%) patients submitted sputum for DST, of whom (163) 95% were positive for Mycobacterium tuberculosis on Xpert MTB/RIF and/or culture and 17 (10%) were rifampicin resistant (9 with MDR-TB and 8 monoresistant to rifampicin). For those without MDR-TB (n = 224), treatment success was 93%. Worse outcomes occurred in those with unknown HIV status (RR: 0.27; 0.05-1.45; P < 0.01) while better outcomes occurred in those who relapsed (RR: 1.06, 95 CI: 1.02-1.10, P = 0.04). Conclusion. In 2013, a high proportion of retreatment patients received DST. Treatment success was good although more needs to be done to systematically increase the final follow-up smear examination. Reasons of high losses to follow-up from "Oueme-Plateau" should be investigated. PMID:27110400

  1. First-Line Treatment for Tuberculosis (TB), Drug Resistant TB -- A Visual Tour

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Drugs First-Line Treatment of TB for Drug- ... ago. See how these drugs work . Multidrug-Resistant Tuberculosis (MDR TB) and Second-Line Treatments MDR TB ...

  2. Transcriptional Adaptation of Drug-tolerant Mycobacterium tuberculosis During Treatment of Human Tuberculosis

    PubMed Central

    Walter, Nicholas D.; Dolganov, Gregory M.; Garcia, Benjamin J.; Worodria, William; Andama, Alfred; Musisi, Emmanuel; Ayakaka, Irene; Van, Tran T.; Voskuil, Martin I.; de Jong, Bouke C.; Davidson, Rebecca M.; Fingerlin, Tasha E.; Kechris, Katerina; Palmer, Claire; Nahid, Payam; Daley, Charles L.; Geraci, Mark; Huang, Laurence; Cattamanchi, Adithya; Strong, Michael; Schoolnik, Gary K.; Davis, John Lucian

    2015-01-01

    Background. Treatment initiation rapidly kills most drug-susceptible Mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged drug exposure. We evaluated drug-tolerant bacilli in human sputum by comparing messenger RNA (mRNA) expression of drug-tolerant bacilli that survive the early bactericidal phase with treatment-naive bacilli. Methods. M. tuberculosis gene expression was quantified via reverse-transcription polymerase chain reaction in serial sputa from 17 Ugandans treated for drug-susceptible pulmonary tuberculosis. Results. Within 4 days, bacterial mRNA abundance declined >98%, indicating rapid killing. Thereafter, the rate of decline slowed >94%, indicating drug tolerance. After 14 days, 16S ribosomal RNA transcripts/genome declined 96%, indicating slow growth. Drug-tolerant bacilli displayed marked downregulation of genes associated with growth, metabolism, and lipid synthesis and upregulation in stress responses and key regulatory categories—including stress-associated sigma factors, transcription factors, and toxin-antitoxin genes. Drug efflux pumps were upregulated. The isoniazid stress signature was induced by initial drug exposure, then disappeared after 4 days. Conclusions. Transcriptional patterns suggest that drug-tolerant bacilli in sputum are in a slow-growing, metabolically and synthetically downregulated state. Absence of the isoniazid stress signature in drug-tolerant bacilli indicates that physiological state influences drug responsiveness in vivo. These results identify novel drug targets that should aid in development of novel shorter tuberculosis treatment regimens. PMID:25762787

  3. Implementing intensified tuberculosis case-finding among street-connected youth and young adults in Kenya

    PubMed Central

    Mercer, T.; Kimani, S.; Braitstein, P.; Buziba, N.; Carter, E. J.

    2016-01-01

    Background: Street-connected youth and young adults (SCY) suffer a myriad of health problems. In Kenya, SCY are at high risk for tuberculosis (TB) due to their congregate living situations. TB screening is not routinely implemented in SCY and there has been no published literature on the burden of TB in SCY in western Kenya. Program description: In 2011, the AMPATH TB Program, an experienced TB screening program, partnered with the Tumaini Center, a trusted street youth organization, to conduct intensified case finding (ICF) for pulmonary TB among SCY. Our program aimed to investigate the numbers of SCY who reported symptoms and those diagnosed with smear-positive pulmonary TB, and link SCY with TB to treatment. Results: Of 116 SCY who were screened, 114 (98%) had a positive questionnaire; 104 (90%) provided a spot sputum sample, 39 (34%) provided a morning sputum sample, and 111 (97%) reported cough of >2 weeks. One street youth tested smear-positive for TB and was treated through to cure. Conclusions: Implementing TB ICF is feasible in low-resource settings through unique collaborations between health care programs and community-based organizations. In addition to identifying smear-positive TB, our program uncovered a high burden of respiratory symptoms among SCY in Eldoret, Kenya. PMID:27358809

  4. Tuberculosis

    MedlinePlus

    Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air when a person with ...

  5. Major Delays in the Diagnosis and Management of Tuberculosis Patients in Nepal

    PubMed Central

    Mahato, Roshan Kumar; Vaeteewootacharn, Kriangsak; Koju, Rajendra; Bhattarai, Ratna

    2015-01-01

    Background Early diagnosis is a determining factor for spread of tuberculosis. Delay in diagnosis and treatment of tuberculosis geometrically increases spread and infectivity of the disease and is associated with higher risk of mortality. Aim The present study aimed to investigate the length of delays in diagnosis and treatment among new pulmonary tuberculosis patients in central development region of Nepal. Materials and Methods A cross-sectional study was conducted by administration of structured questionnaire interview and reviewing the medical records of the new sputum smear positive pulmonary tuberculosis cases during January–May 2015. Simple random sampling was applied to select samples from 5 districts of 19 districts comprising at least one each from 3 ecological regions of Nepal. Results A total of 374 new sputum smear positive pulmonary tuberculosis cases were included in the study. The median patient delay, health system delay, and total delay were 32 days, 3 days and 39.5 days respectively. The unacceptable patients delay was 53.21% (95% CI: 48.12-58.29) of all new patients, whereas it was 26.74% (95% CI: 22.23-31.24) for the unacceptable health system delay and the unacceptable total delay was 62.83% (95% CI: 57.91-67.75). Conclusion TB diagnosis and treatment is still a significant problem of Nepal. Majority of unacceptable delays were from patients. Identifying factors influencing delays and developing evidence-based approaches to address those delays will help in advancing tuberculosis prevention and management in low-income settings. PMID:26557545

  6. [Factors affecting the treatment results with pulmonary tuberculosis patients].

    PubMed

    Berezovskiĭ, B A; Salobaĭ, R Iu; Marchak, V V; Popova, I I; Zakopaĭlo, G G; Kucher, V A; Vasylyk, V U; Mikheĭ, L V

    1991-12-01

    A study is presented of the effect of social factors on the outcomes of pulmonary tuberculosis in patients with freshly detected disease mainly in rural localities in 1985-1989. The outcomes of treatment depended mainly on the form and extension of the pathological process and terms of treatment. It was also established that the outcomes of tuberculosis are also influenced by unfavourable social factors which are more pronounced in persons with an extensive process. Treatment results were better in women with higher education than in similarly educator men. Among agricultural workers treatment efficacy was worse than among office workers and housewives. Life in the family effects more favourably treatment results than single life. Treatment results were worse in those living in unsatisfactory conditions, engaged in hard physical work, suffering of concomitant diseases and bad habits.

  7. Tuberculosis case-finding through a village outreach programme in a rural setting in southern Ethiopia: community randomized trial.

    PubMed Central

    Shargie, Estifanos Biru; Mørkve, Odd; Lindtjørn, Bernt

    2006-01-01

    OBJECTIVE: To ascertain whether case-finding through community outreach in a rural setting has an effect on case-notification rate, symptom duration, and treatment outcome of smear-positive tuberculosis (TB). METHODS: We randomly allocated 32 rural communities to intervention or control groups. In intervention communities, health workers from seven health centres held monthly diagnostic outreach clinics at which they obtained sputum samples for sputum microscopy from symptomatic TB suspects. In addition, trained community promoters distributed leaflets and discussed symptoms of TB during house visits and at popular gatherings. Symptomatic individuals were encouraged to visit the outreach team or a nearby health facility. In control communities, cases were detected through passive case-finding among symptomatic suspects reporting to health facilities. Smear-positive TB patients from the intervention and control communities diagnosed during the study period were prospectively enrolled. FINDINGS: In the 1-year study period, 159 and 221 cases of smear-positive TB were detected in the intervention and control groups, respectively. Case-notification rates in all age groups were 124.6/10(5) and 98.1/10(5) person-years, respectively (P = 0.12). The corresponding rates in adults older than 14 years were 207/10(5) and 158/10(5) person-years, respectively (P = 0.09). The proportion of patients with >3 months' symptom duration was 41% in the intervention group compared with 63% in the control group (P<0.001). Pre-treatment symptom duration in the intervention group fell by 55-60% compared with 3-20% in the control group. In the intervention and control groups, 81% and 75%, respectively of patients successfully completed treatment (P = 0.12). CONCLUSION: The intervention was effective in improving the speed but not the extent of case finding for smear-positive TB in this setting. Both groups had comparable treatment outcomes. PMID:16501728

  8. In silico evaluation and exploration of antibiotic tuberculosis treatment regimens

    DOE PAGESBeta

    Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; Kirschner, Denise E.

    2015-11-14

    Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data frommore » non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment. In conclusion, our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.« less

  9. Common types of tuberculosis and co-infection with HIV at private health institutions in Ethiopia: a cross sectional study

    PubMed Central

    2014-01-01

    Background Tuberculosis is a global emergency predominantly affecting developing countries. HIV has been the single most important reason for acquisition of tuberculosis for many patients. Conversely, tuberculosis can result in rapid progression of HIV disease. Ethiopia is a country affected seriously by HIV and tuberculosis. The main aim of this study is assessment of the types of tuberculosis and the extent of HIV infection among tuberculosis patients visiting private health institutions in Amhara region of Ethiopia. Methods The study used a cross sectional method with data collected using well structured pretested questionnaires containing socio-demographic and clinical variables including HIV serostatus. The setting is tuberculosis treatment sites situated at 15 private health institutions in Amhara region. Results A total of 1153 TB patients were included. The proportions of smear positive pulmonary TB, smear negative pulmonary TB, isolated extrapulmonary TB and disseminated TB cases were found to be 29.6%, 22.2%, 43.9% and 2.9%, respectively. TB lymphadenitis accounted for about 61% of the extrapulmonary cases followed by TB pleurisy (10.6%). Seventy percent of the patients had undergone HIV test, and 20% of them were HIV positive. Marital status, patient residence and type of TB are the major determinants of co-infection. Conclusion The occurrence of pulmonary tuberculosis is relatively low. Tuberculosis/HIV co-infection is also lower than other reports. PMID:24708793

  10. Characteristics and Treatment Outcomes of Retreatment Tuberculosis Patients in Benin

    PubMed Central

    Ade, Serge; Adjibodé, Omer; Wachinou, Prudence; Toundoh, Narcisse; Awanou, Bérénice; Agodokpessi, Gildas; Affolabi, Dissou; Adè, Gabriel; Harries, Anthony D.; Anagonou, Séverin

    2016-01-01

    Objective. To determine among retreatment tuberculosis patients in Benin baseline characteristics, culture, and drug sensitivity testing (DST) results and treatment outcomes. Materials and Methods. A retrospective national cohort study of all retreatment tuberculosis patients in Benin in 2013 using registers and treatment cards. Results. Of 3957 patients with tuberculosis, 241 (6%) were retreatment cases. Compared to new pulmonary bacteriologically confirmed tuberculosis (NPBCT) patients, there were significantly higher numbers of males (P = 0.04), patients from “Atlantique-Littoral” (P = 0.006), patients aged 45–64 years (P = 0.007), and HIV-positive patients (P = 0.04) among those retreated. Overall, 171 (71%) patients submitted sputum for DST, of whom (163) 95% were positive for Mycobacterium tuberculosis on Xpert MTB/RIF and/or culture and 17 (10%) were rifampicin resistant (9 with MDR-TB and 8 monoresistant to rifampicin). For those without MDR-TB (n = 224), treatment success was 93%. Worse outcomes occurred in those with unknown HIV status (RR: 0.27; 0.05–1.45; P < 0.01) while better outcomes occurred in those who relapsed (RR: 1.06, 95 CI: 1.02–1.10, P = 0.04). Conclusion. In 2013, a high proportion of retreatment patients received DST. Treatment success was good although more needs to be done to systematically increase the final follow-up smear examination. Reasons of high losses to follow-up from “Oueme-Plateau” should be investigated. PMID:27110400

  11. Prevalence, Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin- Mono-Resistant Pulmonary Tuberculosis in Lima, Peru

    PubMed Central

    Villegas, Leonela; Huaman, Moises A.; Van der Stuyft, Patrick; Gotuzzo, Eduardo; Seas, Carlos

    2016-01-01

    Background Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes. Methods A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment. Results Of 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1–4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9–47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01). Conclusion A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes. PMID:27045684

  12. Mortality of tuberculosis patients in Chennai, India.

    PubMed Central

    Kolappan, C.; Subramani, R.; Karunakaran, K.; Narayanan, P. R.

    2006-01-01

    OBJECTIVE: We aimed to measure the mortality rate and excess general mortality as well as identify groups at high risk for mortality among a cohort of tuberculosis patients treated in Chennai Corporation clinics in south India. METHODS: In this retrospective cohort study we followed up 2674 patients (1800 males and 874 females) who were registered and treated under the DOTS strategy in Chennai Corporation clinics in 2000. The follow-up period from the date of start of treatment to either the date of interview, or death was 600 days. FINDINGS: The mortality rate among this cohort of tuberculosis patients was 60/1000 person-years. The excess general mortality expressed as standardized mortality ratio (SMR) was 6.1 (95% confidence interval (CI)=5.4-6.9). Younger patients, men, patients with Category II disease, patients who defaulted on, or failed courses of treatment, and male smokers who were alcoholics, all had higher mortality ratios when compared to the rest of the cohort. CONCLUSION: The excess mortality in this cohort was six times more than that in the general population. Young age, male sex, smear-positivity, treatment default, treatment failure and the combination of smoking and alcoholism were identified as risk factors for tuberculosis mortality. We suggest that mortality rate and excess mortality be routinely used as a monitoring tool for evaluating the efficiency of the national control programme. PMID:16878229

  13. An approach to the problems of diagnosing and treating adult smear-negative pulmonary tuberculosis in high-HIV-prevalence settings in sub-Saharan Africa.

    PubMed Central

    Harries, A. D.; Maher, D.; Nunn, P.

    1998-01-01

    The overlap between the populations in sub-Saharan Africa infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis has led to an upsurge in tuberculosis cases over the last 10 years. The relative increase in the proportion of notified sputum-smear-negative pulmonary tuberculosis (PTB) cases is greater than that of sputum-smear-positive PTB cases. This is a consequence of the following: the association between decreased host immunity and reduced sputum smear positivity; the difficulty in excluding other HIV-related diseases when making the diagnosis of smear-negative PTB; and an increase in false-negative sputum smears because of overstretched resources. This article examines problems in the diagnosis and treatment of smear-negative PTB in high-HIV-prevalence areas in sub-Saharan Africa. The main issues in diagnosis include: the criteria used to diagnose smear-negative PTB; the degree to which clinicians actually follow these criteria in practice; and the problem of how to exclude other respiratory diseases that can resemble, and be misdiagnosed as, smear-negative PTB. The most important aspect of the treatment of smear-negative PTB patients is abandoning 12-month "standard" treatment regimens in favour of short-course chemotherapy. Operational research is necessary to determine the most cost-effective approaches to the diagnosis and treatment of smear-negative PTB. Nevertheless, substantial improvement could be obtained by implementing the effective measures already available, such as improved adherence to diagnostic and treatment guidelines. PMID:10191561

  14. The Incremental Cost-Effectiveness of Engaging Private Practitioners to Refer Tuberculosis Suspects to DOTS Services in Jogjakarta, Indonesia

    PubMed Central

    Mahendradhata, Yodi; Probandari, Ari; Ahmad, Riris A.; Utarini, Adi; Trisnantoro, Laksono; Lindholm, Lars; van der Werf, Marieke J.; Kimerling, Michael; Boelaert, Marleen; Johns, Benjamin; Van der Stuyft, Patrick

    2010-01-01

    We aimed to evaluate the incremental cost-effectiveness of engaging private practitioners (PPs) to refer tuberculosis (TB) suspects to public health centers in Jogjakarta, Indonesia. Effectiveness was assessed for TB suspects notified between May 2004 and April 2005. Private practitioners referred 1,064 TB suspects, of which 57.5% failed to reach a health center. The smear-positive rate among patients reaching a health center was 61.8%. Two hundred eighty (280) out of a total of 1,306 (21.4%) new smear-positive cases were enrolled through the PPs strategy. The incremental cost-effectiveness ratio per smear-positive case successfully treated for the PPs strategy was US$351.66 (95% CI 322.84–601.33). On the basis of an acceptability curve using the National TB control program's willingness-to-pay threshold (US$448.61), we estimate the probability that the PPs strategy is cost-effective at 66.8%. The strategy of engaging PPs was incrementally cost-effective, although under specific conditions, most importantly a well-functioning public directly observed treatment, short-course (DOTS) program. PMID:20519613

  15. Does the type of treatment supporter influence tuberculosis treatment outcomes in Zimbabwe?

    PubMed

    Mlilo, N; Sandy, C; Harries, A D; Kumar, A M V; Masuka, N; Nyathi, B; Edginton, M; Isaakidis, P; Manzi, M; Siziba, N

    2013-06-21

    Zimbabwe National Tuberculosis Guidelines advise that direct observation of anti-tuberculosis treatment (DOT) can be provided by a family member/relative as a last resort. In 2011, in Nkayi District, of 763 registered tuberculosis (TB) patients, 59 (8%) received health facility-based DOT, 392 (51%) received DOT from a trained community worker and 306 (40%) from a family member/relative. There were no differences in TB treatment outcomes between the three DOT groups, apart from a higher frequency rate of 'no reported outcomes' for those receiving family-based DOT. Family members should be trained to use a suitable DOT support package.

  16. Assessment of linezolid efficacy, safety and tolerability in the treatment of tuberculosis: A retrospective case review.

    PubMed

    Tse-Chang, Alena; Kunimoto, Dennis; Der, Evelina; Ahmed, Rabia

    2013-01-01

    Linezolid is a potentially effective drug for the treatment of patients with drug-resistant tuberculosis. Among 13 patients treated for tuberculosis with linezolid in the present study, nine had treatment success and four remain on treatment. Adverse effects occurred in 11 (85%) patients, of whom three discontinued treatment because of adverse effects. The present study adds to the growing evidence supporting the efficacy of linezolid for tuberculosis, although treatment remains complicated by adverse effects.

  17. 78 FR 66744 - Draft Guidance for Industry on Pulmonary Tuberculosis: Developing Drugs for Treatment; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Pulmonary Tuberculosis... industry entitled ``Pulmonary Tuberculosis: Developing Drugs for Treatment.'' The purpose of the draft... tuberculosis. This guidance applies to the development of a single investigational drug as well as...

  18. Measurement and determinants of tuberculosis outcome in Karonga District, Malawi.

    PubMed Central

    Glynn, J. R.; Warndorff, D. K.; Fine, P. E.; Munthali, M. M.; Sichone, W.; Pönnighaus, J. M.

    1998-01-01

    Evaluation of disease outcome is central to the assessment of tuberculosis (TB) control programmes. In the study reported in this article we examined the factors influencing the measurement of outcome, survival rates during and after treatment, smear conversion rates, and relapse rates for patients diagnosed with TB in a rural area of Malawi between 1986 and mid-1994. Patients with less certain diagnoses of TB were more likely to die than those with confirmed TB, both among those who were seropositive and those who were seronegative to human immunodeficiency virus (HIV). The mortality rate among smear-positive patients with a separate culture-positive specimen was half that of patients with no such diagnostic confirmation. Patients not registered by the Ministry of Health had much higher mortality and default rates than did registered patients. Among smear-positive patients, HIV serostatus was the most important influence on mortality both during and after treatment (crude hazard ratios (95% confidence intervals) = 5.6 (3.0-10) and 7.7 (3.4-17), resp.), but HIV serostatus did not influence smear conversion rates. The initial degree of smear positivity influenced smear conversion rates, but not mortality rates. No significant predictors of relapse were identified. Unless considerable care is taken to include all TB patients, and to exclude nontuberculous patients, recorded TB outcome statistics are difficult to interpret and may be misleading. In populations with high rates of HIV infection, TB target cure rates of 85% are unrealistic. When new interventions are assessed it cannot be assumed that factors which influence the smear conversion rate will also influence the mortality rate. PMID:9744250

  19. Intensified tuberculosis case finding amongst vulnerable communities in southern India.

    PubMed

    Reddy, K K; Ananthakrishnan, R; Jacob, A G; Das, M; Isaakidis, P; Kumar, A M V

    2015-12-21

    India mainly uses passive case finding to detect tuberculosis (TB) patients through the Revised National Tuberculosis Control Programme (RNTCP). An intensified case finding (ICF) intervention was conducted among vulnerable communities in two districts of Karnataka during July-December 2013; 658 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 8.8% relative to the pre-intervention period (July-December 2012) in intervention communities as compared to an 8.6% decrease in communities without the ICF intervention. ICF activities brought TB services closer to vulnerable communities, moderately increasing TB case detection rates.

  20. Turning off the tap: stopping tuberculosis transmission through active case-finding and prompt effective treatment.

    PubMed

    Yuen, Courtney M; Amanullah, Farhana; Dharmadhikari, Ashwin; Nardell, Edward A; Seddon, James A; Vasilyeva, Irina; Zhao, Yanlin; Keshavjee, Salmaan; Becerra, Mercedes C

    2015-12-01

    To halt the global tuberculosis epidemic, transmission must be stopped to prevent new infections and new cases. Identification of individuals with tuberculosis and prompt initiation of effective treatment to rapidly render them non-infectious is crucial to this task. However, in settings of high tuberculosis burden, active case-finding is often not implemented, resulting in long delays in diagnosis and treatment. A range of strategies to find cases and ensure prompt and correct treatment have been shown to be effective in high tuberculosis-burden settings. The population-level effect of targeted active case-finding on reducing tuberculosis incidence has been shown by studies and projected by mathematical modelling. The inclusion of targeted active case-finding in a comprehensive epidemic-control strategy for tuberculosis should contribute substantially to a decrease in tuberculosis incidence. PMID:26515675

  1. Tuberculosis in African Americans: clinical characteristics and outcome.

    PubMed Central

    Funnyé, A. S.; Ganesan, K.; Yoshikawa, T. T.

    1998-01-01

    This study examined the clinical characteristics and outcome of pulmonary tuberculosis in African Americans hospitalized in a teaching hospital in south-central Los Angeles from May 1992 through April 1994. The charts of 41 African Americans with culture-positive Mycobacterium tuberculosis were reviewed. Predisposing factors for pulmonary tuberculosis were identified in nearly half of cases. Cough and fever were the most common symptoms. Seventy-six percent had positive acid-fast bacilli (AFB) smears. Nine patients were human immunodeficiency virus (HIV)-positive, and 6 of 9 HIV-positive patients had positive AFB smears whereas 17 of 19 HIV-negative patients had positive AFB smears. Radiographic changes were not significantly different between HIV-positive and HIV-negative patients. Drug resistance was identified in nine of 31 patients (29%). Eight of 41 patients (19.5%) died, with 2 being drug resistant. Human immunodeficiency virus infection was a major predisposing factor for tuberculosis, and no statistical differences were found in radiographic features or AFB smear positivity between HIV-positive and HIV-negative patients. Drug resistance and mortality were disproportionately high. These results indicate that HIV infection and drug resistance are major problems that predispose for tuberculosis infection and make its treatment difficult. PMID:9510620

  2. Treatment Default amongst Patients with Tuberculosis in Urban Morocco: Predicting and Explaining Default and Post-Default Sputum Smear and Drug Susceptibility Results

    PubMed Central

    Ghali, Iraqi; Kizub, Darya; Billioux, Alexander C.; Bennani, Kenza; Bourkadi, Jamal Eddine; Benmamoun, Abderrahmane; Lahlou, Ouafae; Aouad, Rajae El; Dooley, Kelly E.

    2014-01-01

    Setting Public tuberculosis (TB) clinics in urban Morocco. Objective Explore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance. Design Case-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals’ perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing. Results 91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one’s treatment duration. Age >50 years, never smoking, and having friends who knew one’s diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare. Conclusion The causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings

  3. Tuberculosis.

    PubMed

    Dheda, Keertan; Barry, Clifton E; Maartens, Gary

    2016-03-19

    Although the worldwide incidence of tuberculosis has been slowly decreasing, the global disease burden remains substantial (∼9 million cases and ∼1·5 million deaths in 2013), and tuberculosis incidence and drug resistance are rising in some parts of the world such as Africa. The modest gains achieved thus far are threatened by high prevalence of HIV, persisting global poverty, and emergence of highly drug-resistant forms of tuberculosis. Tuberculosis is also a major problem in health-care workers in both low-burden and high-burden settings. Although the ideal preventive agent, an effective vaccine, is still some time away, several new diagnostic technologies have emerged, and two new tuberculosis drugs have been licensed after almost 50 years of no tuberculosis drugs being registered. Efforts towards an effective vaccine have been thwarted by poor understanding of what constitutes protective immunity. Although new interventions and investment in control programmes will enable control, eradication will only be possible through substantial reductions in poverty and overcrowding, political will and stability, and containing co-drivers of tuberculosis, such as HIV, smoking, and diabetes.

  4. Tuberculosis.

    PubMed

    Dheda, Keertan; Barry, Clifton E; Maartens, Gary

    2016-03-19

    Although the worldwide incidence of tuberculosis has been slowly decreasing, the global disease burden remains substantial (∼9 million cases and ∼1·5 million deaths in 2013), and tuberculosis incidence and drug resistance are rising in some parts of the world such as Africa. The modest gains achieved thus far are threatened by high prevalence of HIV, persisting global poverty, and emergence of highly drug-resistant forms of tuberculosis. Tuberculosis is also a major problem in health-care workers in both low-burden and high-burden settings. Although the ideal preventive agent, an effective vaccine, is still some time away, several new diagnostic technologies have emerged, and two new tuberculosis drugs have been licensed after almost 50 years of no tuberculosis drugs being registered. Efforts towards an effective vaccine have been thwarted by poor understanding of what constitutes protective immunity. Although new interventions and investment in control programmes will enable control, eradication will only be possible through substantial reductions in poverty and overcrowding, political will and stability, and containing co-drivers of tuberculosis, such as HIV, smoking, and diabetes. PMID:26377143

  5. Drug-Induced Hypothyroidism during Anti-Tuberculosis Treatment of Multidrug-Resistant Tuberculosis: Notes from the Field

    PubMed Central

    Anil, Singarajipura; Naik, Balaji; Volkmann, Tyson; Sagili, Karuna D.; Akshatha, Jayachamarajapura S.; Buggi, Shashidhar; Sharada, Manchenahalli A.; Kulkarni, Sudhendra; Chadha, Vineet K.

    2016-01-01

    We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment; the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on anti-retroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted. PMID:27595122

  6. Delamanid expanded access novel treatment of drug resistant tuberculosis

    PubMed Central

    Rustomjee, Roxana; Zumla, Alimuddin

    2015-01-01

    Tuberculosis (TB) remains a global emergency and is one of the most common infectious disease causes of death in developing countries. Current treatment regimens for multi-drug resistant TB are associated with low treatment success rates, are toxic, and require long duration of treatment. The need for shorter and more effective treatment regimens is urgent. Delamanid (Deltyba, or formerly known as OPC-67683) is a new dihydro-imidazooxazole anti-TB drug active against resistant forms of pulmonary TB. Delamanid kills Mycobacterium tuberculosis by inhibiting the synthesis of mycolic acids required for cell wall synthesis. Whilst delamanid has been included in the WHO Model List of Essential Medicine by the World Health Organization Expert Committee on Selection and Use of Essential Medicines and in international guidance for the treatment of multi-drug resistant TB since April 2014, its access in countries with the greatest need, has proven challenging. This review provides an update on currently available clinical safety and efficacy data on delamanid and offers a discussion on research priorities and recommendations for expedited, expanded access. PMID:26604805

  7. Tuberculosis axillary lymph node coexistent breast cancer in adjuvant treatment: case report

    PubMed Central

    Bromberg, Silvio Eduardo; do Amaral, Paulo Gustavo Tenório

    2015-01-01

    Coexistence of breast cancer and tuberculosis is rare. In most cases, involvement by tuberculosis occurs in axillary lymph nodes. We report a case of a 43-years-old patient who had undergone adenomastectomy and left sentinel lymph node biopsy due to a triple negative ductal carcinoma. At the end of adjuvant treatment, the patient had an atypical lymph node in the left axilla. Lymph node was excised, and after laboratory analysis, the diagnosis was ganglion tuberculosis. The patient underwent treatment for primary tuberculosis. The development of these two pathologies can lead to problems in diagnosis and treatment. An accurate diagnosis is important to avoid unnecessary surgical procedures. PMID:26018148

  8. The outcome of tuberculosis treatment in subjects with chronic kidney disease in Brazil: a multinomial analysis*

    PubMed Central

    Reis-Santos, Barbara; Gomes, Teresa; Horta, Bernardo Lessa; Maciel, Ethel Leonor Noia

    2013-01-01

    OBJECTIVE: To analyze the association between clinical/epidemiological characteristics and outcomes of tuberculosis treatment in patients with concomitant tuberculosis and chronic kidney disease (CKD) in Brazil. METHODS: We used the Brazilian Ministry of Health National Case Registry Database to identify patients with tuberculosis and CKD, treated between 2007 and 2011. The tuberculosis treatment outcomes were compared with epidemiological and clinical characteristics of the subjects using a hierarchical multinomial logistic regression model, in which cure was the reference outcome. RESULTS: The prevalence of CKD among patients with tuberculosis was 0.4% (95% CI: 0.37-0.42%). The sample comprised 1,077 subjects. The outcomes were cure, in 58%; treatment abandonment, in 7%; death from tuberculosis, in 13%; and death from other causes, in 22%. The characteristics that differentiated the ORs for treatment abandonment or death were age; alcoholism; AIDS; previous noncompliance with treatment; transfer to another facility; suspected tuberculosis on chest X-ray; positive results in the first smear microscopy; and indications for/use of directly observed treatment, short-course strategy. CONCLUSIONS: Our data indicate the importance of sociodemographic characteristics for the diagnosis of tuberculosis in patients with CKD and underscore the need for tuberculosis control strategies targeting patients with chronic noncommunicable diseases, such as CKD. PMID:24310632

  9. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment.

    PubMed

    Coussens, Anna K; Wilkinson, Robert J; Hanifa, Yasmeen; Nikolayevskyy, Vladyslav; Elkington, Paul T; Islam, Kamrul; Timms, Peter M; Venton, Timothy R; Bothamley, Graham H; Packe, Geoffrey E; Darmalingam, Mathina; Davidson, Robert N; Milburn, Heather J; Baker, Lucy V; Barker, Richard D; Mein, Charles A; Bhaw-Rosun, Leena; Nuamah, Rosamond; Young, Douglas B; Drobniewski, Francis A; Griffiths, Christopher J; Martineau, Adrian R

    2012-09-18

    Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

  10. [Tuberculosis].

    PubMed

    Iinuma, Y

    2000-11-01

    The incidence of tuberculosis in Japan is the highest among developed countries, with approximately 42,000 new cases reported in 1997, marking the first increase in 38 years. The growing incidence among the elderly and group infections among young adults may be responsible for this increase. Infection with tubercle bacilli(TB) occurs via airborne transmission, which involves dissemination of either airborne droplet nuclei on evaporated droplets that may remain suspended in the air for long periods of time. Microorganisms carried in this manner can be dispersed widely by air currents, therefore, special air handling and ventilation are required to prevent airborne transmission. Patients with infectious TB must be placed in a single room with negative pressure and a ventilation rate of 6 or more air changes per hour. Health care workers must wear an N95 mask when entering the room, and if an incident involving possible TB infection occurs in the hospital, the concerned people should be examined for Tuberculin reaction. Two to 12 weeks after the TB infection has occurred, the tuberculin reaction converts to positive. However, most Japanese people have been vaccinated with BCG, so assessment of the results is difficult. A comparison of the diameter of erythema before and after the potential infection may be the most confirmatory. If latent TB infection is suspected, preventive therapy with isoniazid must be considered. Special biohazard systems in the clinical laboratory and autopsy room have also been proposed to prevent TB dispersal. DOTS(Directly Observed Treatment, Short-course) is useful to prevent the emergence of multi-drug-resistant TB. In some areas of Japan that have low levels of compliance with TB therapy, trials of DOTS have been started. PMID:11132556

  11. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  12. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  13. Gastric Cancer with Peritoneal Tuberculosis: Challenges in Diagnosis and Treatment

    PubMed Central

    Alshahrani, Amer Saeed

    2016-01-01

    Herein, we report a 39-year-old female patient presenting with gastric cancer and tuberculous peritonitis. The differential diagnosis between advanced gastric cancer with peritoneal carcinomatosis and early gastric cancer with peritoneal tuberculosis (TB), and the treatment of these two diseases, were challenging in this case. Physicians should have a high index of suspicion for peritoneal TB if the patient has a history of this disease, especially in areas with a high incidence of TB, such as South Korea. An early diagnosis is critical for patient management and prognosis. A surgical approach including tissue biopsy or laparoscopic exploration is recommended to confirm the diagnosis. PMID:27433397

  14. Tuberculosis incidence among contacts of active pulmonary tuberculosis

    PubMed Central

    Cailleaux-Cezar, M.; de A. Melo, D.; Xavier, G. M.; de Salles, C. L. G.; de Mello, F. C. Q.; Ruffino-Netto, A.; Golub, J. E.; Efron, A.; Chaisson, R. E.; Conde, M. B.

    2013-01-01

    SUMMARY BACKGROUND Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients aged ≤15 years with a tuberculin skin test (TST) ≥10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST ≥15 mm regardless of previous BCG vaccination. OBJECTIVE To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment. DESIGN Retrospective cohort study. Contacts aged between 12 and 15 years and those aged >15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study. RESULTS TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100 000 population. Risk of TB was greater among the 349 contacts with TST ≥5 mm (5.4%) compared to the 318 contacts with TST < 5 mm (0.9%; RR 6.04, 95%CI 1.7–20.6). CONCLUSION The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration ≥5 mm was the only variable that predicted the development of TB disease within 2 years. PMID:19146746

  15. Hepatotoxicity during Treatment for Tuberculosis in People Living with HIV/AIDS

    PubMed Central

    Araújo-Mariz, Carolline; Lopes, Edmundo Pessoa; Acioli-Santos, Bartolomeu; Maruza, Magda; Montarroyos, Ulisses Ramos; Ximenes, Ricardo Arraes de Alencar; Lacerda, Heloísa Ramos; Miranda-Filho, Demócrito de Barros; de Albuquerque, Maria de Fátima P. Militão

    2016-01-01

    Hepatotoxicity is frequently reported as an adverse reaction during the treatment of tuberculosis. The aim of this study was to determine the incidence of hepatotoxicity and to identify predictive factors for developing hepatotoxicity after people living with HIV/AIDS (PLWHA) start treatment for tuberculosis. This was a prospective cohort study with PLWHA who were monitored during the first 60 days of tuberculosis treatment in Pernambuco, Brazil. Hepatotoxicity was considered increased levels of aminotransferase, namely those that rose to three times higher than the level before initiating tuberculosis treatment, these levels being associated with symptoms of hepatitis. We conducted a multivariate logistic regression analysis and the magnitude of the associations was expressed by the odds ratio with a confidence interval of 95%. Hepatotoxicity was observed in 53 (30.6%) of the 173 patients who started tuberculosis treatment. The final multivariate logistic regression model demonstrated that the use of fluconazole, malnutrition and the subject being classified as a phenotypically slow acetylator increased the risk of hepatotoxicity significantly. The incidence of hepatotoxicity during treatment for tuberculosis in PLWHA was high. Those classified as phenotypically slow acetylators and as malnourished should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis. The use of fluconazole should be avoided during tuberculosis treatment in PLWHA. PMID:27332812

  16. Tuberculosis

    MedlinePlus

    ... to address TB and HIV coinfection around the world? The President’s U.S. President's Emergency Plan for AIDS ... of those suffering from HIV/AIDS around the world. PEPFAR’s Global Fund to Fight AIDS, Tuberculosis and ...

  17. Tuberculosis Treatment Completion Rates in Southern New Mexico Colonias.

    PubMed

    Holden, Maria Arroyo; Huttlinger, Kathleen; Schultz, Pamela; Mullins, Iris; Forster-Cox, Sue

    2016-04-01

    TB medication completion treatment rates for active TB patients living in impoverished US-Mexico border communities called colonias in southern New Mexico counties are unknown. It might be suspected that residents of colonias have lower completion rates than those living in incorporated and medically more accessible areas. A retrospective record review of closed TB case records from 1993 to 2010 of southern New Mexico border counties, was conducted using a modified version of the New Mexico Department of Health Tuberculosis Targeted Health Assessment/History form (Appendix 1). Study findings reveal that despite their unincorporated status, poorer living conditions and questionable legal status, colonia TB patients had a higher medication completion rate than their non-colonia counterparts. A robust New Mexico TB treatment program contributed to high completion rates with death being the number-one reason for treatment non-completion in both colonia and non-colonias.

  18. Surgical treatment of complications of pulmonary tuberculosis, including drug-resistant tuberculosis.

    PubMed

    Madansein, Rajhmun; Parida, Shreemanta; Padayatchi, Nesri; Singh, Nalini; Master, Iqbal; Naidu, Kantharuben; Zumla, Alimuddin; Maeurer, Markus

    2015-03-01

    Surgery for drug-resistant tuberculosis has been shown to be safe and effective, with similar level of mortalities associated with surgical intervention observed with that for lung cancer. While surgery has been an option to treat TB in the pre-antibiotic era, it is now increasingly used to treat complications of pulmonary TB, particularly in patients with drug-resistant TB who do not respond to medical treatment. The two most frequent indications for lung resection in drug- resistant TB, are i) failed medical treatment with persistent sputum positivity or ii) patients who have had medical treatment and are sputum negative, but with persistent localized cavitary disease or bronchiectasis. Massive hemoptysis is a potentially life-threatening complication of TB. Lung resection is potentially curative in patients with massive hemoptysis and cavitary or bronchiectatic disease. Bronchial artery embolization in these patients has a high success rate but bears also the risk of recurrence. Lung resection can be safely undertaken in selected patients with HIV co-infection and pulmonary complications of TB. Ambulatory drainage is a novel, safe, affordable and effective method of draining a chronic TB associated empyema thoracis. We review here the current surgical treatment of the complications of pulmonary TB and discuss the experience from the Durban Cardiothoracic Surgery Unit for the surgical treatment of patients with complicated pulmonary TB. PMID:25809758

  19. [Clinical aspects and treatment of tuberculosis of respiratory organs in adolescents under present epidemiological conditions].

    PubMed

    Stoiunin, M B; Chebotareva, T V; Repina, E S; Kosina, A M; Tochilova, T P; Kolotilova, O N

    1999-01-01

    The paper summarizes the results of clinical observations of 55 teenagers suffering from active respiratory tuberculosis. It defines risk factors for this disease in adolescents. Emphasis is laid on the current pathomorphology and a great variety of clinical types of tuberculosis. Treatment of tuberculosis is ascertained to be preferred by using the short-term intensive chemotherapy regimen recommended by the World Health Organization, which is intended to cure most patients in the shortest period as compared with existing routine regimens.

  20. American Thoracic Society. Medical Section of the American Lung Association: Treatment of tuberculosis and tuberculosis infection in adults and children.

    PubMed

    1986-08-01

    Treatment of tuberculosis: A 6-month regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 months followed by isoniazid and rifampin for 4 months is effective treatment in patients with fully susceptible organisms who comply with the treatment regimen. It may be advisable to include ethambutol in the initial phase when isoniazid resistance is suspected. A 9-month regimen consisting of isoniazid and rifampin is also highly successful. The need for an additional drug in the initial phase is not certain unless isoniazid resistance is suspected, in which case ethambutol should be included until susceptibility tests have been reported. In the presence of documented resistance to isoniazid, rifampin and ethambutol, perhaps supplemented initially by pyrazinamide, should be given for minimum of 12 months. Children should be treated in essentially the same ways as adults using appropriately adjusted doses of the drugs. However, consideration must be given to the important differences in the approach to management in children. Extrapulmonary tuberculosis should be managed according to the principles and with the drug regimens outlined to pulmonary tuberculosis. The major determinant of the outcome of treatment is patient compliance. Careful attention should be paid to measures designed to foster compliance and to ensure that patients take the drugs as prescribed. Treatment of tuberculous infection: Preventive therapy with isoniazid given for 6 to 12 months is effective in decreasing the risk of future tuberculosis. (ABSTRACT TRUNCATED AT 250 WORDS)

  1. Recent advances in the diagnosis and treatment of childhood tuberculosis

    PubMed Central

    Kumar, Mani Kant; Kumar, Prashant; Singh, Anjali

    2015-01-01

    Despite over 2.3 million (26% of global burden) cases of tuberculosis (TB) in India the accurate diagnosis of childhood TB remains a major challenge. Children with TB usually have paucibacillary disease and contribute little to disease transmission within the community. Consequently the treatment of children with TB is often not considered a priority by TB control programmes. Adequate and timely assessment of TB infection in childhood could diminish epidemiological burden as underdiagnosed pediatric patients can eventually evolve in to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. In this review we discuss the most important recent advances in the diagnosis of childhood TB: (1) Symptom-based approaches, (2) novel immune-based approaches, including in vitro interferon-γ IGRA release assays IGRA tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for TB diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active TB in children, nevertheless establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge. PMID:26283820

  2. Recent advances in the diagnosis and treatment of childhood tuberculosis.

    PubMed

    Kumar, Mani Kant; Kumar, Prashant; Singh, Anjali

    2015-01-01

    Despite over 2.3 million (26% of global burden) cases of tuberculosis (TB) in India the accurate diagnosis of childhood TB remains a major challenge. Children with TB usually have paucibacillary disease and contribute little to disease transmission within the community. Consequently the treatment of children with TB is often not considered a priority by TB control programmes. Adequate and timely assessment of TB infection in childhood could diminish epidemiological burden as underdiagnosed pediatric patients can eventually evolve in to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. In this review we discuss the most important recent advances in the diagnosis of childhood TB: (1) Symptom-based approaches, (2) novel immune-based approaches, including in vitro interferon-γ IGRA release assays IGRA tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for TB diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active TB in children, nevertheless establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge.

  3. Vitamin D deficiency in Malawian adults with pulmonary tuberculosis: risk factors and treatment outcomes

    PubMed Central

    Mwandumba, H. C.; Kamdolozi, M.; Shani, D.; Chisale, B.; Dutton, J.; Khoo, S. H.; Allain, T. J.; Davies, G. R.

    2015-01-01

    SUMMARY SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to anti-tuberculosis treatment. OBJECTIVES: To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS: The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti-tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS: Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment. PMID:26162355

  4. Local problems, local solutions: improving tuberculosis control at the district level in Malawi.

    PubMed Central

    Kelly, P. M.

    2001-01-01

    OBJECTIVE: To examine the causes of a low cure rate at the district level of a tuberculosis (TB) control programme and to formulate, implement, and evaluate an intervention to improve the situation. METHODS: The study setting was Mzuzu (population 60,000), where the annual smear-positive pulmonary TB incidence was 160 per 100,000 and the human immunodeficiency virus (HIV) seroprevalence was 67% among TB patients. There is one TB treatment unit, but several other organizations are involved with TB control. An examination of case-holding activities was carried out, potential areas for improvement were identified, and interventions performed. FINDINGS: In 1990-91, the cure rate was 24% among smear-positive cases (29% among survivors to end of treatment). Problems identified included a fragmented TB control programme; inadequate training and supervision; suboptimal recording of patients' addresses; and nonadherence to national TB control programme protocols. These problems were addressed, and in 1992-93 the cure rate rose to 68% (relative risk (RR) = 2.85 (95% confidence interval (CI) = 1.63, 4.96)) and to 92% among survivors to the end of treatment (RR = 3.12 (95% CI = 1.84, 5.29)). High cure rates are therefore achievable despite high HIV prevalence. CONCLUSIONS: Simple, inexpensive, local programmatic interventions can dramatically improve TB case holding. This study demonstrates the need for evaluation, training, and supervision at all levels of the programme. PMID:11242817

  5. Low access to a highly effective therapy: a challenge for international tuberculosis control.

    PubMed Central

    Dye, Christopher; Watt, Catherine J.; Bleed, Daniel

    2002-01-01

    OBJECTIVE: To determine the scale of the tuberculosis (TB) problem facing the international Stop TB Partnership by measuring the gap between present rates of case detection and treatment success, and the global targets (70% and 85%, respectively) to be reached by 2005 under the WHO DOTS strategy. METHODS: We analysed case notifications submitted annually to WHO from up to 202 (of 210) countries and territories between 1980 and 2000, and the results of treatment for patients registered between 1994 and 1999. FINDINGS: Many of the 148 national DOTS programmes in existence by the end of 2000 have shown that they can achieve high treatment success rates, close to or exceeding the target of 85%. However, we estimate that only 27% of all the new smear-positive cases that arose in 2000 were notified under DOTS, and only 19% were successfully treated. The increment in case-finding has been steady at about 133 000 additional smear-positive cases in each year since 1994. In the interval 1999- 2000, more than half of the extra cases notified under DOTS were in Ethiopia, India, Myanmar, the Philippines, and South Africa. CONCLUSION: With the current rate of progress in DOTS expansion, the target of 70% case detection will not be reached until 2013. To reach this target by 2005, DOTS programmes must find an additional 333 000 cases each year. The challenge now is to show that DOTS expansion in the major endemic countries can significantly accelerate case finding while maintaining high cure rates. PMID:12131999

  6. Early stationary phase culture supernatant accelerates growth of sputum cultures collected after initiation of anti-tuberculosis treatment.

    PubMed

    Kolwijck, E; Friedrich, S O; Karinja, M N; van Ingen, J; Warren, R M; Diacon, A H

    2014-07-01

    We investigated the effect of Mycobacterium tuberculosis culture supernatant added to sputum cultures collected during the first 8 weeks of anti-tuberculosis treatment. With ongoing treatment duration, time to culture positivity decreased significantly in supernatant-enriched cultures, possibly due to stimulation of dormant or slowly metabolizing M. tuberculosis cells.

  7. Social, economic and operational research on tuberculosis: recent studies and some priority questions.

    PubMed

    Murray, C J

    1991-12-01

    Social, economic and operational research has already contributed to the growing global awareness of the neglected burden of tuberculosis on individuals, families and communities. These studies have also illustrated that short-course chemotherapy for smear-positive pulmonary tuberculosis is a highly cost-effective tool for combatting tuberculosis. In the present work, the author examines the costs and effectiveness of the national tuberculosis programmes in Malawi, Mozambique and Tanzania. Chemotherapy for smear-positive tuberculosis is found to be among the most cost-effective health interventions known, costing 1-4 US dollars per year of life saved. In all situations, short-course chemotherapy is found to be more cost-effective than standard 12-month chemotherapy. General conclusions about the role of hospitalization are difficult to make; its cost-effectiveness depends on local patterns of compliance and the cost of hospitalization. Because more than three-quarters of the benefits of chemotherapy for smear-positive tuberculosis are due to transmission reduction, treating HIV sero-positives, smear-positives is probably cost-effective.

  8. Tuberculosis control and economic recession: longitudinal study of data from 21 European countries, 1991–2012

    PubMed Central

    Reeves, Aaron; Basu, Sanjay; McKee, Martin; Sandgren, Andreas; Semenza, Jan C

    2015-01-01

    Abstract Objective To investigate whether the economic recession affected the control of tuberculosis in the European Union. Methods Multivariate regression models were used to quantify the association between gross domestic product, public health expenditure and tuberculosis case detection rates, using data from 21 European Union member states (1991–2012). The estimated changes in case detection attributable to the recession were combined with mathematical models of tuberculosis transmission, to project the potential influence of the recession on tuberculosis epidemiology until 2030. Findings Between 1991 and 2007, detection rates for sputum-smear-positive tuberculosis in the European Union were stable at approximately 85%. During the economic recession (2008–2011) detection rates declined by a mean of 5.22% (95% confidence interval, CI: 2.54–7.90) but treatment success rates showed no significant change (P = 0.62). A fall in economic output of 100 United States dollars per capita was associated with a 0.22% (95% CI: 0.05–0.39) mean reduction in the tuberculosis case detection rate. An equivalent fall in spending on public health services was associated with a 2.74% (95% CI: 0.31–5.16) mean reduction in the detection rate. Mathematical models suggest that the recession and consequent austerity policies will lead to increases in tuberculosis prevalence and tuberculosis-attributable mortality that are projected to persist for over a decade. Conclusion Across the European Union, reductions in spending on public health services appear to have reduced tuberculosis case detection and to have increased the long-term risk of a resurgence in the disease. PMID:26240458

  9. A Prospective Study of Tuberculosis Drug Susceptibility in Sabah, Malaysia, and an Algorithm for Management of Isoniazid Resistance

    PubMed Central

    Rashid Ali, Muhammad Redzwan S.; Parameswaran, Uma; William, Timothy; Bird, Elspeth; Wilkes, Christopher S.; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M.; Ralph, Anna P.

    2015-01-01

    Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5–9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB. PMID:25838829

  10. Preventing tuberculosis among health workers in Malawi.

    PubMed Central

    Harries, A. D.; Hargreaves, N. J.; Gausi, F.; Kwanjana, J. H.; Salaniponi, F. M.

    2002-01-01

    OBJECTIVE: Following the introduction of guidelines for the control of tuberculosis (TB) infection in all hospitals in Malawi, a study was carried out to determine whether the guidelines were being implemented, the time between admission to hospital and the diagnosis of pulmonary TB had been reduced, and the annual case notification rates among health workers had fallen and were comparable to those of primary-school teachers. METHODS: The study involved 40 district and mission hospitals. Staff and patients were interviewed in order to determine whether the guidelines had been adopted. In four hospitals the diagnostic process in patients with smear-positive pulmonary TB was evaluated before and after the introduction of the guidelines, with the aid of case notes and TB registers. In all hospitals the proportion of health workers registered with TB before and after the guidelines were introduced, in 1996 and 1999, respectively, was determined by conducting interviews and consulting staff lists and TB registers. A similar method was used to determine the proportion of primary-school teachers who were registered with TB in 1999. FINDINGS: The guidelines were not uniformly implemented. Only one hospital introduced voluntary counselling and testing for its staff. Most hospitals stated that they used rapid systems to diagnose pulmonary TB. However, there was no significant change in the interval between admission and diagnosis or between admission and treatment of patients with smear-positive pulmonary TB. The TB case notification rate for 2979 health workers in 1999 was 3.2%; this did not differ significantly from the value of 3.7% for 2697 health workers in 1996 but was significantly higher than that of 1.8% for 4367 primary-school teachers in 1999. CONCLUSION: The introduction of guidelines for the control of TB infection is an important intervention for reducing nosocomial transmission of the disease, but rigorous monitoring and follow-up are needed in order to ensure

  11. Impact of latent infection treatment in indigenous populations.

    PubMed

    Yuhara, Lucia Suemi; Sacchi, Flávia Patussi Correia; Croda, Julio

    2013-01-01

    The aims of the present study were to identify risk factors associated with latent tuberculosis (TB), examine the development of active disease among contacts, and assess the effectiveness of treating latent infection in indigenous Brazilians from January 2006 to December 2011. This was a retrospective study consisting of 1,371 tuberculosis contacts, 392 of whom underwent treatment for latent infection. Morbidity-from-TB data were obtained from the Information System for Disease Notification (SINAN) database, and the contacts' data were collected from the clinical records using forms employed by Special Department of Indigenous Health (SESAI) multidisciplinary teams, according to SESAI's instructions. The variables that were associated with latent infection among the contacts were age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02-1.04) and close contact with a smear-positive index case (OR: 2.26, 95% CI: 1.59-3.22). The variables associated with the development of active TB among the contacts were a tuberculin skin test (TST) ≥10 mm (relative risk [RR]: 1.12, 95% CI: 1.07-1.17), age (RR: 1.01, 95% CI: 1.00-1.03), and treatment of latent infection (RR: 0.03, 95% CI: 0.01-0.27). The estimated number of latent infection treatments needed to prevent one case of active TB among the contacts was 51 treatments (95% CI: 33-182). In contacts with TST ≥10 mm, 10 (95% CI: 6-19) latent infection treatments were necessary to prevent one case of active TB. Age and close contact with a smear-positive index case were associated with latent TB. Screening with TST is a high priority among individuals contacting smear-positive index cases. Age and TST are associated with the development of active TB among contacts, and treatment of latent infection is an effective measure to control TB in indigenous communities. PMID:23936264

  12. Recent advances in tuberculosis: New drugs and treatment regimens.

    PubMed

    Sloan, Derek J; Davies, Geraint R; Khoo, Saye H

    2013-06-01

    The current treatment regimen against drug susceptible tuberculosis (DS-TB) was defined by the 1980s. Since then the emergence of the global HIV pandemic and the escalation of drug resistant (DR-) forms of TB have presented new challenges for therapeutic research. Priority goals include shortening DS-TB treatment, improving DR-TB treatment and making combined TB-HIV therapy easier. To help achieve these goals, a range of new drugs and treatment strategies are currently being evaluated. Phase IIb and III clinical trials are ongoing to assess combinations involving the high-dose rifamycins, the 8-methoxyquinolones, a diarylquinoline (bedaquiline) and the nitroimidazoles. Other compounds (e.g. novel oxazolidinones and ethylenediamines) are at earlier stages of clinical development. Overall, there are grounds for optimism that recent advances will contribute towards achievement of new treatment regimens in the foreseeable future. However, long-term investment, political commitment and scientific endeavour are crucial to ensure that progress is sustained and the benefits of recent advances reach those in the greatest need.

  13. Endobronchial valve treatment of destructive multidrug-resistant tuberculosis

    PubMed Central

    Levin, A.; Felker, I.; Tceymach, E.; Krasnov, D.

    2016-01-01

    SUMMARY BACKGROUND: In accordance with the existing hypothesis, the application of an endobronchial valve (EbV) leads to selective curative atelectasis of the affected part of the lung, contributing to early closure of cavities. OBJECTIVE: To assess the effect of EbV treatment on the course of tuberculosis (TB). METHODS: We compared the efficacy of EbV treatment and complex second-line treatment in treating patients with destructive pulmonary multidrug-resistant TB (MDR-TB). Bacteriological conversion and closure of cavities were selected as criteria to assess the effectiveness of EbV application. A total of 102 patients with destructive MDR-TB were enrolled into the study and randomly divided into two groups: 49 patients had an EbV installed (intervention group) and 53 patients received complex second-line treatment (control group). Complex chemotherapy was administered to both groups throughout the study period. RESULTS: The cure rate in the short- and long-term follow-up periods in the intervention group was shown to be much higher, 95.9% by bacteriological conversion and 67.3% by cavity closure. On comparison with the control group, this was respectively 37.7% and 20.7% (P < 0.0001). CONCLUSIONS: The application of EbV treatment can significantly improve the effectiveness of second-line chemotherapy regimens in MDR-TB patients. PMID:27776598

  14. Host Immune Responses Differ between M. africanum- and M. tuberculosis-Infected Patients following Standard Anti-tuberculosis Treatment

    PubMed Central

    Tientcheu, Leopold D.; Haks, Mariëlle C.; Agbla, Schadrac C.; Sutherland, Jayne S.; Adetifa, Ifedayo M.; Donkor, Simon; Quinten, Edwin; Daramy, Mohammed; Antonio, Martin; Kampmann, Beate; Ottenhoff, Tom H. M.; Dockrell, Hazel M.; Ota, Martin O.

    2016-01-01

    Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1α were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-γ and TNF-α production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility. PMID:27192147

  15. The dual epidemics of tuberculosis and AIDS: ethical and policy issues in screening and treatment.

    PubMed Central

    Bayer, R; Dubler, N N; Landesman, S

    1993-01-01

    As the recent increase in cases of tuberculosis is addressed, there is a danger that the need for increased protection of the public health will create a climate in which the rights of individuals with tuberculosis and human immunodeficiency virus (HIV) infection may be disregarded. This paper considers ethical and policy issues in the control of tuberculosis. The authors conclude that mandatory HIV testing is not critical to effective tuberculosis control, and that although individuals infected with HIV are at increased risk for developing tuberculosis, exclusionary employment practices are not justified. Because failure to complete the course of tuberculosis treatment increases the prospect that drug-resistant strains will develop, it is crucial to require all those who commence treatment to complete their therapy. To ensure the completion of treatment, special attention must be paid to the needs of the homeless, drug users, and those with psychiatric impairments. In addition, all tuberculosis patients should begin their posthospital care under direct observation. Patients who fail to complete treatment despite efforts to encourage and facilitate their cooperation should be subject to confinement after a hearing with full due process protections. PMID:8484443

  16. Sex-related trends in non-conversion of new smear-positive tuberculosis patients in the Free State, South Africa.

    PubMed

    Heunis, J C; Kigozi, N G; van der Merwe, S; Chikobvu, P; Beyers, N

    2014-03-21

    Contexte : Province de l'Etat Libre, Afrique du Sud.Objectif : Examiner les tendances en fonction du sexe de la nonconversion des frottis de crachats après 2 mois chez des nouveaux cas de tuberculose (TB) à frottis positifs pendant une période où la stratégie DOTS opérait.Schéma : Réalisation d'une étude rétrospective de cohorte des cas de TB enregistrés entre 2003 et 2009. La non-conversion était définie par un résultat de frottis positif après 2 mois de traitement. Des analyses descriptives et de modèles linéaires généralisés ont été réalisées et les tendances de non conversion à 2 mois en fonction du sexe ont été estimées.Résultats : Le taux d'ensemble de non conversion était de 12,5% chez les hommes et de 9,3% chez les femmes. La non conversion était significativement associée à l'âge chez les hommes (P < 0,001). Le taux de non conversion a significativement diminué entre 2003 et 2009 de 15,9% à 10,8% chez les hommes (P < 0,001) et de 12% à 6,6% chez les femmes (P < 0,001). Le taux moyen de déclin de la non-conversion était plus élevé chez les femmes à 1% (IC95% 0,8–1,2%) que chez les hommes à 0,8% (IC95% 0,5–1%). En 2009, le risque de non conversion était plus élevé de 60% chez les hommes (RR 1,60; IC95% 1,37–1,86).Conclusion : Le déclin de la tendance à la non-conversion du frottis de crachats après 2 mois de traitement a mis en évidence le succès relatif de la stratégie DOTS dans la lutte contre la TB, avec un meilleur résultat chez les femmes que chez les hommes. Les interventions devraient tenir compte du sexe et de l'âge des patients afin d'améliorer le taux de conversion du frottis de crachats à 2 mois.

  17. Gatifloxacin for short, effective treatment of multidrug-resistant tuberculosis.

    PubMed

    Chiang, C-Y; Van Deun, A; Rieder, H L

    2016-09-01

    The 9-month regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) piloted in Bangladesh and used, with modifications, in Cameroon and Niger, has achieved treatment success in a very large proportion of patients; gatifloxacin (GFX) is likely to have played a critical role in this success. Two months after the publication of a study reporting that GFX and not moxifloxacin (MFX) was associated with dysglycaemia, the manufacturer announced the withdrawal of GFX from the market. The findings of that study may have less significance for the majority of MDR-TB patients living in high-incidence countries who are much younger, have a lower risk of dysglycaemia and suffer from a highly fatal condition. The problem of dysglycaemia is not limited to GFX use and may occur with other fluoroquinolones; furthermore, GFX-associated dysglycemia was manageable among those MDR-TB patients in Bangladesh and Niger in whom it occurred. GFX has now become unavailable in Bangladesh, Cameroon, Niger and other countries piloting the shorter MDR-TB regimens, depriving resource-poor countries of an efficacious, effective and inexpensive drug with a demonstrated good safety profile for the given indication. There is little reason not to make GFX available for MDR-TB treatment as long as the superiority of non-GFX-based MDR-TB regimens is not demonstrated. PMID:27510237

  18. Tuberculosis treatment outcome monitoring in European Union countries: systematic review

    PubMed Central

    van Hest, Rob; Ködmön, Csaba; Verver, Suzanne; Erkens, Connie G.M.; Straetemans, Masja; Manissero, Davide; de Vries, Gerard

    2013-01-01

    Treatment success measured by treatment outcome monitoring (TOM) is a key programmatic output of tuberculosis (TB) control programmes. We performed a systematic literature review on national-level TOM in the 30 European Union (EU)/European Economic Areas (EEA) countries to summarise methods used to collect and report data on TOM. Online reference bibliographic databases PubMed/MEDLINE and EMBASE were searched to identify relevant indexed and non-indexed literature published between January 2000 and August 2010. The search strategy resulted in 615 potentially relevant indexed citations, of which 27 full-text national studies (79 data sets) were included for final analysis. The selected studies were performed in 10 EU/EEA countries and gave a fragmented impression of TOM in the EU/EEA. Publication year, study period, sample size, databases, definitions, variables, patient and outcome categories, and population subgroups varied widely, portraying a very heterogeneous picture. This review confirmed previous reports of considerable heterogeneity in publications of TOM results across EU/EEA countries. PubMed/MEDLINE and EMBASE indexed studies are not a suitable instrument to measure representative TOM results for the 30 EU/EEA countries. Uniform and complete reporting to the centralised European Surveillance System will produce the most timely and reliable results of TB treatment outcomes in the EU/EEA. PMID:22790913

  19. Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence

    PubMed Central

    Stevenson, Catherine R; Forouhi, Nita G; Roglic, Gojka; Williams, Brian G; Lauer, Jeremy A; Dye, Chirstopher; Unwin, Nigel

    2007-01-01

    Background Tuberculosis (TB) remains a major cause of mortality in developing countries, and in these countries diabetes prevalence is increasing rapidly. Diabetes increases the risk of TB. Our aim was to assess the potential impact of diabetes as a risk factor for incident pulmonary tuberculosis, using India as an example. Methods We constructed an epidemiological model using data on tuberculosis incidence, diabetes prevalence, population structure, and relative risk of tuberculosis associated with diabetes. We evaluated the contribution made by diabetes to both tuberculosis incidence, and to the difference between tuberculosis incidence in urban and rural areas. Results In India in 2000 there were an estimated 20.7 million adults with diabetes, and 900,000 incident adult cases of pulmonary tuberculosis. Our calculations suggest that diabetes accounts for 14.8% (uncertainty range 7.1% to 23.8%) of pulmonary tuberculosis and 20.2% (8.3% to 41.9%) of smear-positive (i.e. infectious) tuberculosis. We estimate that the increased diabetes prevalence in urban areas is associated with a 15.2% greater smear-positive tuberculosis incidence in urban than rural areas – over a fifth of the estimated total difference. Conclusion Diabetes makes a substantial contribution to the burden of incident tuberculosis in India, and the association is particularly strong for the infectious form of tuberculosis. The current diabetes epidemic may lead to a resurgence of tuberculosis in endemic regions, especially in urban areas. This potentially carries a risk of global spread with serious implications for tuberculosis control and the achievement of the United Nations Millennium Development Goals. PMID:17822539

  20. Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina.

    PubMed

    Herrero, María Belén; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres

    2015-01-01

    OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors. METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed. RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070). CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation. PMID:26270011

  1. Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina

    PubMed Central

    Herrero, María Belén; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres

    2015-01-01

    OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors. METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed. RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070). CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation. PMID:26270011

  2. Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina.

    PubMed

    Herrero, María Belén; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres

    2015-01-01

    OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors. METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed. RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070). CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation.

  3. ART uptake, its timing and relation to anti-tuberculosis treatment outcomes among HIV-infected TB patients

    PubMed Central

    Harries, A. D.; Mutasa-Apollo, T.; Sandy, C.; Murimwa, T.; Mugurungi, O.

    2012-01-01

    Setting: All public health facilities in two provinces of Zimbabwe. Objective: To determine, among tuberculosis (TB) patients with human immunodeficiency virus (HIV) registered in 2010, 1) the proportion started on antiretroviral treatment (ART), 2) the timing of ART in relation to the start of anti-tuberculosis treatment, and 3) whether timing of ART influenced anti-tuberculosis treatment outcomes. Design: Retrospective cohort study. Results: Of the 2655 HIV-positive TB patients, 1115 (42%) were documented as receiving ART. Of these, 178 (16%) started ART prior to anti-tuberculosis treatment. Of those who started after anti-tuberculosis treatment, 17% started within 2 weeks, 43% between 2 and 8 weeks and 40% after 8 weeks. Treatment success in the cohort was 82%, with 14% deaths before completion of anti-tuberculosis treatment. Not receiving ART during anti-tuberculosis treatment was associated with lower anti-tuberculosis treatment success (adjusted RR 0.70, 95%CI 0.53–0.91) and more deaths (adjusted RR 3.43, 95%CI 2.2–5.36). There were no differences in TB treatment outcomes by timing of ART initiation. Conclusion: ART uptake is low given the improved treatment outcomes in those put on ART during anti-tuberculosis treatment. Better integration of HIV and TB services is needed to ensure increased coverage and earlier ART uptake. PMID:26392951

  4. [Therapy and Rehabilitation of Patients with Pulmonary Tuberculosis and Different Treatment Adherence].

    PubMed

    Rubleva, N V; Kolomiets, V M; Kochetkova, E Ya

    2016-01-01

    The pulmonary tuberculosis process as dependent on the disease form and the therapy efficacy with the use of Cycloferon in the treatment scheme were investigated. The study had two stages. At the first stage the data concerning 358 patients with primary pulmonary tuberculosis and infiltration (93 patients) or degradation (89 patients) and 176 patients with pulmonary fibrocavernous tuberculosis were analysed. At the second stage the efficacy of the treatment schemes applied to the patients with pulmonary fibrocavernous tuberculosis was compared. The etiotropic therapy intensive phase was applied to all the patients. Moreover, 56 patients (group 1) under the therapy and rehabilitatinon were treated with Cycloferon in a dose of 0.25 administered intramuscularly twice a week (not less than 16 injections for the course), 60 patients (group 2) were treated with Omega 3, 30 patients (group 3) were given the standard complex (vitamins and tonics), 30 patients (group 4) were under the etiotropic therapy alone. The following additional factors promoting progression and aggravation of the tuberculosis process were confirmed: degradation at the time of the disease diagnosis, high resistance of the pathogen to antituberculosis drugs, low adherence to the treatment, social desadaptation and especially psychofunctional state of the patients. The use of Cycloferon in the schemes of the intensive phase treatment of the primary fibrocavernous tuberculosis resulted in reduction of the intoxication signs, bacteria isolation, positive dynamics of the cavity healing, lower lung infiltration and consequently high frequency of the treatment positive outcomes (94.1 ± 3.33%). PMID:27337863

  5. Detection of lipoarabinomannan as a diagnostic test for tuberculosis.

    PubMed Central

    Sada, E; Aguilar, D; Torres, M; Herrera, T

    1992-01-01

    A coagglutination technique was established for the detection of lipoarabinomannan of Mycobacterium tuberculosis in human serum samples and evaluated for its utility in the diagnosis of tuberculosis at the Instituto Nacional de Enfermedades Respiratorias in Mexico City. The test had a sensitivity of 88% in patients with sputum-smear-positive active pulmonary tuberculosis. The sensitivity in patients with active pulmonary tuberculosis negative for acid-fast bacilli in sputum was 67%. Less favorable results were obtained for patients with AIDS and tuberculosis, with a sensitivity of 57%. The specificity in control patients with lung diseases different from tuberculosis and in healthy subjects was 100%. The positive predictive value was 100%, and the negative predictive value for patients with sputum-positive active pulmonary tuberculosis was 97%. The results of this study suggest that the detection of lipoarabinomannan is an accurate test for the diagnosis of pulmonary tuberculosis. PMID:1401008

  6. Detection of lipoarabinomannan as a diagnostic test for tuberculosis.

    PubMed

    Sada, E; Aguilar, D; Torres, M; Herrera, T

    1992-09-01

    A coagglutination technique was established for the detection of lipoarabinomannan of Mycobacterium tuberculosis in human serum samples and evaluated for its utility in the diagnosis of tuberculosis at the Instituto Nacional de Enfermedades Respiratorias in Mexico City. The test had a sensitivity of 88% in patients with sputum-smear-positive active pulmonary tuberculosis. The sensitivity in patients with active pulmonary tuberculosis negative for acid-fast bacilli in sputum was 67%. Less favorable results were obtained for patients with AIDS and tuberculosis, with a sensitivity of 57%. The specificity in control patients with lung diseases different from tuberculosis and in healthy subjects was 100%. The positive predictive value was 100%, and the negative predictive value for patients with sputum-positive active pulmonary tuberculosis was 97%. The results of this study suggest that the detection of lipoarabinomannan is an accurate test for the diagnosis of pulmonary tuberculosis.

  7. High Prevelance of Rifampin-Monoresistant Tuberculosis: A Retrospective Analysis among Iranian Pulmonary Tuberculosis Patients

    PubMed Central

    Velayati, Ali Akbar; Farnia, Parissa; Mozafari, Mohadese; Sheikholeslami, Maryam Fatemeh; Karahrudi, Mona Afraei; Tabarsi, Payam; Hoffner, Sven

    2014-01-01

    We determined the prevalence of rifampin-monoresistant tuberculosis (RMR-TB) in Iran. Because development of RMR-TB is not common, we also identified the major risk factors associated with RMR-TB reported from different provinces of Iran. Data for 3,020 TB patients who remained or became smear positive after two, four, six, and nine months of standard first-line chemotherapy were retrospectively analyzed. Of 3,020 patients, 1,242 patients (41.1%) were culture and DNA positive for Mycobacterium tuberculosis. Of these patients, 73 (7.4%) patients had monoresistant isolates to rifampin, which was significantly higher than that for multidrug-resistant TB (5.8%). The average rate of RMR-TB in the studied population ranged from 5% to 10%. Classical investigation showed that 33.6% of patients had either a previous or family history of TB. Molecular epidemiology methods (i.e., spoligotyping and Mycobacterium intespersed repetitive unit–variable number tandem repeat), defined transmission link in three clusters (13%). These results outline the urgent need for a comprehensive plan for detection and treatment of RMR-TB cases. PMID:24189362

  8. Determinants of Default from Tuberculosis Treatment among Patients with Drug-Susceptible Tuberculosis in Karachi, Pakistan: A Mixed Methods Study

    PubMed Central

    Chida, Natasha; Ansari, Zara; Hussain, Hamidah; Jaswal, Maria; Symes, Stephen; Khan, Aamir J.; Mohammed, Shama

    2015-01-01

    Purpose Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy. Methods In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013. Results Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04–1.71), being 35–59 years of age (OR: 1.54, 95% CI: 1.14–2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17–2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35–59 years of age (aOR: 1.49, 95% CI: 1.10–2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12–2.77) were associated with default. Conclusions In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative

  9. Pharmaceutical aerosols for the treatment and prevention of Tuberculosis

    PubMed Central

    Hanif, Shumaila N. M.; Garcia-Contreras, Lucila

    2012-01-01

    Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB) is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments. Optimization of formulations and delivery systems for anti-TB vaccines and drugs, as well as the proper selection of the animal model to evaluate those is of paramount importance if novel vaccines or drug treatments are to be successful. Pharmaceutical aerosols for patient use are generated from metered dose inhalers, nebulizers, and dry powder inhalers (DPIs). In addition to the advantages of providing more efficient delivery of the drug, low cost, and portability, pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage forms and do not require refrigeration. Methods to manufacture dry powders in respirable sizes include micronization, spray drying, and other proprietary technologies. Inhalable dry powders are characterized in terms of their drug content, particle size, and dispersibility to ensure deposition in the appropriate lung region and effective aerosolization from the device. These methods will be illustrated as they were applied for the manufacture and characterization of powders containing anti-tubercular agents and vaccines for pulmonary administration. The influence of formulation, selection of animal model, method of aerosol generation, and administration on the efficacy demonstrated in a given study will be illustrated by the evaluation of pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by our

  10. Pharmaceutical aerosols for the treatment and prevention of tuberculosis.

    PubMed

    Hanif, Shumaila N M; Garcia-Contreras, Lucila

    2012-01-01

    Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB) is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments. Optimization of formulations and delivery systems for anti-TB vaccines and drugs, as well as the proper selection of the animal model to evaluate those is of paramount importance if novel vaccines or drug treatments are to be successful. Pharmaceutical aerosols for patient use are generated from metered dose inhalers, nebulizers, and dry powder inhalers (DPIs). In addition to the advantages of providing more efficient delivery of the drug, low cost, and portability, pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage forms and do not require refrigeration. Methods to manufacture dry powders in respirable sizes include micronization, spray drying, and other proprietary technologies. Inhalable dry powders are characterized in terms of their drug content, particle size, and dispersibility to ensure deposition in the appropriate lung region and effective aerosolization from the device. These methods will be illustrated as they were applied for the manufacture and characterization of powders containing anti-tubercular agents and vaccines for pulmonary administration. The influence of formulation, selection of animal model, method of aerosol generation, and administration on the efficacy demonstrated in a given study will be illustrated by the evaluation of pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by our

  11. A tuberculosis nationwide prevalence survey in Gambia, 2012

    PubMed Central

    Kendall, Lindsay; Bashorun, Adedapo; Linda, Christopher; Omoleke, Semeeh; Jeffries, David; Maane, Rahmatulai; Alorse, Beatrice Dei; Alorse, William Dei; Okoi, Catherine Bi; Mlaga, Kodjovi D; Kinteh, Ma Ansu; Donkor, Simon; de Jong, Bouke C; Antonio, Martin; d’Alessandro, Umberto

    2016-01-01

    Abstract Objective To estimate the population prevalence of active pulmonary tuberculosis in Gambia. Methods Between December 2011 and January 2013, people aged ≥ 15 years participating in a nationwide, multistage cluster survey were screened for active pulmonary tuberculosis with chest radiography and for tuberculosis symptoms. For diagnostic confirmation, sputum samples were collected from those whose screening were positive and subjected to fluorescence microscopy and liquid tuberculosis cultures. Multiple imputation and inverse probability weighting were used to estimate tuberculosis prevalence. Findings Of 100 678 people enumerated, 55 832 were eligible to participate and 43 100 (77.2%) of those participated. A majority of participants (42 942; 99.6%) were successfully screened for symptoms and by chest X-ray. Only 5948 (13.8%) were eligible for sputum examination, yielding 43 bacteriologically confirmed, 28 definite smear-positive and six probable smear-positive tuberculosis cases. Chest X-ray identified more tuberculosis cases (58/69) than did symptoms alone (43/71). The estimated prevalence of smear-positive and bacteriologically confirmed pulmonary tuberculosis were 90 (95% confidence interval, CI: 53–127) and 212 (95% CI: 152–272) per 100 000 population, respectively. Tuberculosis prevalence was higher in males (333; 95% CI: 233–433) and in the 35–54 year age group (355; 95% CI: 219–490). Conclusion The burden of tuberculosis remains high in Gambia but lower than earlier estimates of 490 per 100 000 population in 2010. Less than half of all cases would have been identified based on smear microscopy results alone. Successful control efforts will require interventions targeting men, increased access to radiography and more accurate, rapid diagnostic tests. PMID:27274595

  12. Serum Concentrations of Trace Elements in Patients with Tuberculosis and Its Association with Treatment Outcome.

    PubMed

    Choi, Rihwa; Kim, Hyoung-Tae; Lim, Yaeji; Kim, Min-Ji; Kwon, O Jung; Jeon, Kyeongman; Park, Hye Yun; Jeong, Byeong-Ho; Koh, Won-Jung; Lee, Soo-Youn

    2015-07-01

    Deficiencies in essential trace elements are associated with impaired immunity in tuberculosis infection. However, the trace element concentrations in the serum of Korean patients with tuberculosis have not yet been investigated. This study aimed to compare the serum trace element concentrations of Korean adult patients with tuberculosis with noninfected controls and to assess the impact of serum trace element concentration on clinical outcome after antituberculosis treatment. The serum concentrations of four trace elements in 141 consecutively recruited patients with tuberculosis and 79 controls were analyzed by inductively coupled plasma-mass spectrometry. Demographic characteristics were also analyzed. Serum cobalt and copper concentrations were significantly higher in patients with tuberculosis compared with controls, while zinc and selenium concentrations were significantly lower (p < 0.01). Moreover, serum selenium and zinc concentrations were positively correlated (ρ = 0.41, p < 0.05). A high serum copper concentration was associated with a worse clinical outcome, as assessed after one month of antituberculosis therapy. Specifically, culture-positive patients had higher serum copper concentrations than culture-negative patients (p < 0.05). Patients with tuberculosis had altered serum trace element concentrations. Further research is needed to elucidate the roles of individual trace elements and to determine their clinical impact on patients with tuberculosis.

  13. pH-Responsive Isoniazid-Loaded Nanoparticles Markedly Improve Tuberculosis Treatment in Mice.

    PubMed

    Hwang, Angela A; Lee, Bai-Yu; Clemens, Daniel L; Dillon, Barbara Jane; Zink, Jeffrey I; Horwitz, Marcus A

    2015-10-01

    Tuberculosis is a major global health problem for which improved therapeutics are needed to shorten the course of treatment and combat emergence of drug resistance. Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of mononuclear phagocytes. As such, it is an ideal pathogen for nanotherapeutics because macrophages avidly ingest nanoparticles even without specific targeting molecules. Hence, a nanoparticle drug delivery system has the potential to target and deliver high concentrations of drug directly into M. tuberculosis-infected cells-greatly enhancing efficacy while avoiding off-target toxicities. Stimulus-responsive mesoporous silica nanoparticles of two different sizes, 100 and 50 nm, are developed as carriers for the major anti-tuberculosis drug isoniazid in a prodrug configuration. The drug is captured by the aldehyde-functionalized nanoparticle via hydrazone bond formation and coated with poly(ethylene imine)-poly(ethylene glycol) (PEI-PEG). The drug is released from the nanoparticles in response to acidic pH at levels that naturally occur within acidified endolysosomes. It is demonstrated that isoniazid-loaded PEI-PEG-coated nanoparticles are avidly ingested by M. tuberculosis-infected human macrophages and kill the intracellular bacteria in a dose-dependent manner. It is further demonstrated in a mouse model of pulmonary tuberculosis that the nanoparticles are well tolerated and much more efficacious than an equivalent amount of free drug.

  14. Tuberculosis in Elephants: Antibody Responses to Defined Antigens of Mycobacterium tuberculosis, Potential for Early Diagnosis, and Monitoring of Treatment

    PubMed Central

    Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Olsen, John H.; Ball, Ray; Dumonceaux, Genevieve; Dunker, Freeland; Buckley, Carol; Richard, Michael; Murray, Suzan; Payeur, Janet B.; Andersen, Peter; Pollock, John M.; Mikota, Susan; Miller, Michele; Sofranko, Denise; Waters, W. Ray

    2006-01-01

    Tuberculosis (TB) in elephants is a re-emerging zoonotic disease caused primarily by Mycobacterium tuberculosis. Current diagnosis relies on trunk wash culture, the only officially recognized test, which has serious limitations. Innovative and efficient diagnostic methods are urgently needed. Rapid identification of infected animals is a crucial prerequisite for more effective control of TB, as early diagnosis allows timely initiation of chemotherapy. Serology has diagnostic potential, although key antigens have not been identified and optimal immunoassay formats are not established. To characterize the humoral responses in elephant TB, we tested 143 serum samples collected from 15 elephants over time. These included 48 samples from five culture-confirmed TB cases, of which four were in Asian elephants infected with M. tuberculosis and one was in an African elephant with Mycobacterium bovis. Multiantigen print immunoassay (MAPIA) employing a panel of 12 defined antigens was used to identify serologic correlates of active disease. ESAT-6 was the immunodominant antigen recognized in elephant TB. Serum immunoglobulin G antibodies to ESAT-6 and other proteins were detected up to 3.5 years prior to culture of M. tuberculosis from trunk washes. Antibody levels to certain antigens gradually decreased in response to antitubercular therapy, suggesting the possibility of treatment monitoring. In addition to MAPIA, serum samples were evaluated with a recently developed rapid test (RT) based on lateral flow technology (ElephantTB STAT-PAK). Similarly to MAPIA, infected elephants were identified using the RT up to 4 years prior to positive culture. These findings demonstrate the potential for TB surveillance and treatment monitoring using the RT and MAPIA, respectively. PMID:16829608

  15. Successful treatment of spleen tuberculosis in a patient with human immunodeficiency virus infection.

    PubMed

    Maserati, R; Seminari, E; Scudeller, L; Rizzi, L; Benedetti, M; Minoli, L

    1999-04-01

    Tuberculosis in human immunodeficiency virus (HIV)-infected patients may act as a cofactor that accelerates the clinical course of HIV infection, and, indeed, HIV-infected patients with tuberculosis have a reduced survival rate compared to those without tuberculosis. Diagnosis of tuberculosis in HIV-positive patients can be difficult because of nonspecific symptoms and the time required for the identification of mycobacteria by means of culture techniques. Recently, antiretroviral combination therapies have improved the outcome of several acquired immune deficiency syndrome (AIDS)-associated conditions. Unfortunately, the use of antiretroviral therapy for patients coinfected with HIV and Mycobacterium tuberculosis is still to be fully evaluated. The complexity of side-effects due to antituberculosis medication and drug interaction represent important issues and combining an effective anti-HIV treatment with antituberculosis therapy is still a clinical challenge. We discuss here a case of spleen tuberculosis in a human immunodeficiency virus-positive patient who had a successful response after a diagnostic splenectomy and medical treatment that included classical antituberculosis treatment associated with antiretroviral therapy without protease inhibitors.

  16. Evaluation of Hepatoprotective Effect of Silymarin Among Under Treatment Tuberculosis Patients: A Randomized Clinical Trial

    PubMed Central

    Marjani, Majid; Baghaei, Parvaneh; Kazempour Dizaji, Mehdi; Gorji Bayani, Pegah; Fahimi, Fanak; Tabarsi, Payam; Velayati, Ali Akbar

    2016-01-01

    Abstract: Hepatic toxicity is the most serious adverse effect of anti-tuberculosis drugs. This study was performed to evaluate the efficacy of silymarin as a hepatoprotective herbal agent. In a randomized double blind clinical trial, 70 new cases of pulmonary tuberculosis were divided into two groups. The intervention group was assigned to receive silymarin and the control group received placebo. Tuberculosis was treated by classic regimen consisting isoniazid, rifampin, pyrazinamide and ethambutol. No statistically significant difference was found between the two groups concerning the frequency of drug induced liver injury or mild elevation of liver enzymes. Silymarin was safe without any major side effect. Our results showed no significant hepatoprotective effect of silymarin among patients on tuberculosis treatment. PMID:27610165

  17. Evaluation of Hepatoprotective Effect of Silymarin Among Under Treatment Tuberculosis Patients: A Randomized Clinical Trial.

    PubMed

    Marjani, Majid; Baghaei, Parvaneh; Kazempour Dizaji, Mehdi; Gorji Bayani, Pegah; Fahimi, Fanak; Tabarsi, Payam; Velayati, Ali Akbar

    2016-01-01

    Hepatic toxicity is the most serious adverse effect of anti-tuberculosis drugs. This study was performed to evaluate the efficacy of silymarin as a hepatoprotective herbal agent. In a randomized double blind clinical trial, 70 new cases of pulmonary tuberculosis were divided into two groups. The intervention group was assigned to receive silymarin and the control group received placebo. Tuberculosis was treated by classic regimen consisting isoniazid, rifampin, pyrazinamide and ethambutol. No statistically significant difference was found between the two groups concerning the frequency of drug induced liver injury or mild elevation of liver enzymes. Silymarin was safe without any major side effect. Our results showed no significant hepatoprotective effect of silymarin among patients on tuberculosis treatment. PMID:27610165

  18. Evaluation of Hepatoprotective Effect of Silymarin Among Under Treatment Tuberculosis Patients: A Randomized Clinical Trial

    PubMed Central

    Marjani, Majid; Baghaei, Parvaneh; Kazempour Dizaji, Mehdi; Gorji Bayani, Pegah; Fahimi, Fanak; Tabarsi, Payam; Velayati, Ali Akbar

    2016-01-01

    Abstract: Hepatic toxicity is the most serious adverse effect of anti-tuberculosis drugs. This study was performed to evaluate the efficacy of silymarin as a hepatoprotective herbal agent. In a randomized double blind clinical trial, 70 new cases of pulmonary tuberculosis were divided into two groups. The intervention group was assigned to receive silymarin and the control group received placebo. Tuberculosis was treated by classic regimen consisting isoniazid, rifampin, pyrazinamide and ethambutol. No statistically significant difference was found between the two groups concerning the frequency of drug induced liver injury or mild elevation of liver enzymes. Silymarin was safe without any major side effect. Our results showed no significant hepatoprotective effect of silymarin among patients on tuberculosis treatment.

  19. Ethical aspects of directly observed treatment for tuberculosis: a cross-cultural comparison

    PubMed Central

    2013-01-01

    Background Tuberculosis is a major global public health challenge, and a majority of countries have adopted a version of the global strategy to fight Tuberculosis, Directly Observed Treatment, Short Course (DOTS). Drawing on results from research in Ethiopia and Norway, the aim of this paper is to highlight and discuss ethical aspects of the practice of Directly Observed Treatment (DOT) in a cross-cultural perspective. Discussion Research from Ethiopia and Norway demonstrates that the rigid enforcement of directly observed treatment conflicts with patient autonomy, dignity and integrity. The treatment practices, especially when imposed in its strictest forms, expose those who have Tuberculosis to extra burdens and costs. Socially disadvantaged groups, such as the homeless, those employed as day labourers and those lacking rights as employees, face the highest burdens. Summary From an ethical standpoint, we argue that a rigid practice of directly observed treatment is difficult to justify, and that responsiveness to social determinants of Tuberculosis should become an integral part of the management of Tuberculosis. PMID:23819555

  20. The zebrafish guide to tuberculosis immunity and treatment.

    PubMed

    Ramakrishnan, Lalita

    2013-01-01

    During the past 12 years, we have developed the zebrafish as a model for the study of tuberculosis pathogenesis and immunology. We have taken advantage of the optical transparency and the genetic and pharmacological tractability of the developing zebrafish to monitor infection in real time. Detailed information about the sequential interactions among the host and the pathogen, the cell types, and the molecules involved has yielded surprising insights into this ancient disease. We have identified a number of host evasion strategies deployed by pathogenic mycobacteria as well as host responses that provide broad insights into host immunity. Many of these discoveries have relevance to human tuberculosis and suggest new therapeutic avenues for tuberculosis as well as other inflammatory diseases.

  1. Functional and phenotypic changes in monocytes from patients with tuberculosis are reversed with treatment.

    PubMed

    Sánchez, María D; García, Yoenis; Montes, Carlos; París, Sara C; Rojas, Mauricio; Barrera, Luis F; Arias, Mauricio A; García, Luis F

    2006-08-01

    Alterations of monocyte/macrophages have been reported in patients with tuberculosis (TB), but their significance is poorly understood. Blood mononuclear cells from patients with different clinical forms of TB, at various times of anti-TB treatment, and healthy tuberculin positive individuals, were double-stained for CD14 plus CD206, TLR-2, IFN-gammaR1, CD40, HLA-DR, CD36 and CD163, and analyzed by flow cytometry. Monocytes were infected with Mycobacterium tuberculosis H37Rv and 24h later the phenotype, induction of necrosis and apoptosis and production of tumor necrosis factor TNFalpha, interleukin (IL)-10 and IL-12p40 were determined. TB patients presented higher percentage of CD14+ cells but lower percentage of CD14+DR+ and CD14+CD36+ cells. Expression of CD14, HLA-DR and CD36 was decreased in TB patients. Normal percentages and expression were restored during anti-TB treatment. Monocytes from TB patients underwent necrosis and apoptosis after M. tuberculosis infection, whereas monocytes from healthy controls exhibited only apoptosis. Anti-TB treatment reverted necrosis. There were no differences between the various clinical forms of TB. In vitro M. tuberculosis infection decreased expression of the membrane molecules studied. HLA-DR and CD36 inhibition correlated with induction of apoptosis. Restoration of monocyte alterations during anti-TB treatment suggests that such alterations may be caused by the high M. tuberculosis load present during active disease.

  2. [THE RESULTS OF IMPLEMENTATION OF THE INTERNATIONAL BANK FOR RECONSTRUCTION AND DEVELOPMENT LOAN PROJECT "PREVENTION, DIAGNOSIS, AND TREATMENT OF TUBERCULOSIS AND AIDS", A "TUBERCULOSIS" COMPONENT].

    PubMed

    2010-01-01

    Due to the implementation of the International Bank for Reconstruction and Development (IBRD) loan project "Prevention, diagnosis, treatment of tuberculosis and AIDS", a "Tuberculosis" component that is an addition to the national tuberculosis control program in 15 subjects of the Russian Federation, followed up by the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences, the 2005-2008 measures stipulated by the Project have caused substantial changes in the organization of tuberculosis control: implementation of Orders Nos. 109, 50, and 690 and supervision of their implementation; modernization of the laboratories of the general medical network and antituberbulosis service (404 kits have been delivered for clinical diagnostic laboratories and 12 for bacteriological laboratories, including BACTEC 960 that has been provided in 6 areas); 91 training seminars have been held at the federal and regional levels; 1492 medical workers have been trained in the detection, diagnosis, and treatment of patients with tuberculosis; 8 manuals and guidelines have been prepared and sent to all areas. In the period 2005-2008, the tuberculosis morbidity and mortality rates in the followed-up areas reduced by 1.2 and 18.6%, respectively. The analysis of patient cohorts in 2007 and 2005 revealed that the therapeutic efficiency evaluated from sputum smear microscopy increased by 16.3%; there were reductions in the proportion of patients having ineffective chemotherapy (from 16.1 to 11.1%), patients who died from tuberculosis (from 11.6 to 9.9%), and those who interrupted therapy ahead of time (from 11.8 to 7.8%). Implementation of the IBR project has contributed to the improvement of the national strategy and the enhancement of the efficiency of tuberculosis control.

  3. Radioiodinated DPA-713 imaging correlates with bactericidal activity of tuberculosis treatments in mice.

    PubMed

    Ordonez, Alvaro A; Pokkali, Supriya; DeMarco, Vincent P; Klunk, Mariah; Mease, Ronnie C; Foss, Catherine A; Pomper, Martin G; Jain, Sanjay K

    2015-01-01

    Current tools for monitoring response to tuberculosis treatments have several limitations. Noninvasive biomarkers could accelerate tuberculosis drug development and clinical studies, but to date little progress has been made in developing new imaging technologies for this application. In this study, we developed pulmonary single-photon emission computed tomography (SPECT) using radioiodinated DPA-713 to serially monitor the activity of tuberculosis treatments in live mice, which develop necrotic granulomas and cavitary lesions. C3HeB/FeJ mice were aerosol infected with Mycobacterium tuberculosis and administered either a standard or a highly active bedaquiline-containing drug regimen. Serial (125)I-DPA-713 SPECT imaging was compared with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and standard microbiology. Ex vivo studies were performed to characterize and correlate DPA-713 imaging with cellular and cytokine responses. Pulmonary (125)I-DPA-713 SPECT, but not (18)F-FDG PET, was able to correctly identify the bactericidal activities of the two tuberculosis treatments as early as 4 weeks after the start of treatment (P < 0.03). DPA-713 readily penetrated the fibrotic rims of necrotic and cavitary lesions. A time-dependent decrease in both tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels was observed with treatments, with (125)I-DPA-713 SPECT correlating best with tissue TNF-α levels (ρ = 0.94; P < 0.01). (124)I-DPA-713 was also evaluated as a PET probe and demonstrated a 4.0-fold-higher signal intensity in the infected tuberculous lesions than uninfected controls (P = 0.03). These studies provide proof of concept for application of a novel noninvasive imaging biomarker to monitor tuberculosis treatments, with the potential for application for humans. PMID:25403669

  4. Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice

    PubMed Central

    Ordonez, Alvaro A.; Pokkali, Supriya; DeMarco, Vincent P.; Klunk, Mariah; Mease, Ronnie C.; Foss, Catherine A.; Pomper, Martin G.

    2014-01-01

    Current tools for monitoring response to tuberculosis treatments have several limitations. Noninvasive biomarkers could accelerate tuberculosis drug development and clinical studies, but to date little progress has been made in developing new imaging technologies for this application. In this study, we developed pulmonary single-photon emission computed tomography (SPECT) using radioiodinated DPA-713 to serially monitor the activity of tuberculosis treatments in live mice, which develop necrotic granulomas and cavitary lesions. C3HeB/FeJ mice were aerosol infected with Mycobacterium tuberculosis and administered either a standard or a highly active bedaquiline-containing drug regimen. Serial 125I-DPA-713 SPECT imaging was compared with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and standard microbiology. Ex vivo studies were performed to characterize and correlate DPA-713 imaging with cellular and cytokine responses. Pulmonary 125I-DPA-713 SPECT, but not 18F-FDG PET, was able to correctly identify the bactericidal activities of the two tuberculosis treatments as early as 4 weeks after the start of treatment (P < 0.03). DPA-713 readily penetrated the fibrotic rims of necrotic and cavitary lesions. A time-dependent decrease in both tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels was observed with treatments, with 125I-DPA-713 SPECT correlating best with tissue TNF-α levels (ρ = 0.94; P < 0.01). 124I-DPA-713 was also evaluated as a PET probe and demonstrated a 4.0-fold-higher signal intensity in the infected tuberculous lesions than uninfected controls (P = 0.03). These studies provide proof of concept for application of a novel noninvasive imaging biomarker to monitor tuberculosis treatments, with the potential for application for humans. PMID:25403669

  5. Directly observed treatment, short-course strategy and multidrug-resistant tuberculosis: are any modifications required?

    PubMed Central

    Bastian, I.; Rigouts, L.; Van Deun, A.; Portaels, F.

    2000-01-01

    Multidrug-resistant tuberculosis (MDRTB) should be defined as tuberculosis with resistance to at least isoniazid and rifampicin because these drugs are the cornerstone of short-course chemotherapy, and combined isoniazid and rifampicin resistance requires prolonged treatment with second-line agents. Short-course chemotherapy is a key ingredient in the tuberculosis control strategy known as directly observed treatment, short-course (DOTS). For populations in which multidrug-resistant tuberculosis is endemic, the outcome of the standard short-course chemotherapy regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of multidrug-resistant tuberculosis. These "DOTS-plus for MDRTB programmes" may need to modify all five elements of the DOTS strategy: the treatment may need to be individualized rather than standardized; laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility testing; reliable supplies of a wide range of expensive second-line agents would have to be supplied; operational studies would be required to determine the indications for and format of the expanded programmes; financial and technical support from international organizations and Western governments would be needed in addition to that obtained from local governments. PMID:10743297

  6. Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment.

    PubMed

    Axelsson-Robertson, Rebecca; Rao, Martin; Loxton, Andre G; Walzl, Gerhard; Bates, Matthew; Zumla, Alimuddin; Maeurer, Markus

    2015-03-01

    Anti-tuberculosis drug treatment is known to affect the number, phenotype, and effector functionality of antigen-specific T-cells. In order to objectively gauge Mycobacterium tuberculosis (MTB)-specific CD8+ T-cells at the single-cell level, we developed soluble major histocompatibility complex (MHC) class I multimers/peptide multimers, which allow analysis of antigen-specific T-cells without ex vivo manipulation or functional tests. We constructed 38 MHC class I multimers covering some of the most frequent MHC class I alleles (HLA-A*02:01, A*24:02, A*30:01, A*30:02, A*68:01, B*58:01, and C*07:01) pertinent to a South African or Zambian population, and presenting the following MTB-derived peptides: the early expressed secreted antigens TB10.4 (Rv0288), Ag85B (Rv1886c), and ESAT-6 (Rv3875), as well as intracellular enzymes, i.e., glycosyltransferase 1 (Rv2957), glycosyltransferase 2 (Rv2958c), and cyclopropane fatty acid synthase (Rv0447c). Anti-TB treatment appeared to impact on the frequency of multimer-positive CD8+ T-cells, with a general decrease after 6 months of therapy. Also, a reduction in the total central memory CD8+ T-cell frequencies, as well as the antigen-specific compartment in CD45RA-CCR7+ T-cells was observed. We discuss our findings on the basis of differential dynamics of MTB-specific T-cell frequencies, impact of MTB antigen load on T-cell phenotype, and antigen-specific T-cell responses in tuberculosis.

  7. Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease.

    PubMed

    Raju, Ravikiran M; Raju, Sagar M; Zhao, Yanlin; Rubin, Eric J

    2016-03-01

    The nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis or Mycobacterium leprae, are a diverse group of pathogens that collectively cause a substantive but often unappreciated worldwide burden of illness. Although NTMs may cause illness similar to M. tuberculosis, these pathogens generally do not respond to classic tuberculosis (TB) drug regimens, resulting in misdiagnosis and poor treatment, particularly in resource-poor settings. Although a few high-quality epidemiologic surveys have been made on the topic, existing evidence suggests that NTM-associated disease is much more common than previously thought: more common than TB in the industrialized world and likely increasing in prevalence globally. Despite this evidence, these organisms remain markedly understudied, and few international grants support basic science and clinical research. Here we suggest that the considerable efforts in developing new treatments and diagnostics for TB can be harnessed in the fight against NTM-associated illnesses.

  8. A registry-based cohort study of pulmonary tuberculosis treatment outcomes in Istanbul, Turkey.

    PubMed

    Babalik, Aylin; Kilicaslan, Zeki; Caner, S Sevkan; Gungor, Gokay; Ortakoylu, M Gonenc; Gencer, Serap; McCurdy, Stephen A

    2013-01-01

    The aim of this study is to evaluate the treatment outcomes and identify factors associated with adverse tuberculosis treatment outcomes for bacteriologically confirmed pulmonary tuberculosis. Treatment outcomes of pulmonary tuberculosis were evaluated retrospectively among 11,186 smear- and/or culture-positive patients treated between 2006 and 2009 in Istanbul, Turkey. Adverse treatment outcomes were identified in 1,010 (9.0%) patients including death (1.8%), treatment default (6.1%), and treatment failure (1.1%). Factors associated with adverse treatment outcomes included being born abroad (odds ratios [OR], 5.38; 95% confidence intervals [CI], 3.67-7.91), history of tuberculosis treatment (OR, 3.77; 95% CI, 3.26-4.36), age > 65 years (OR, 2.79; 95% CI, 2.21-3.53), and male gender (OR, 1.91; 95% CI, 1.59-2.27). Death was most strongly associated with age > 65 years (OR, 45.1; 95% CI, 27.0-75.6), followed by treatment default with history of interrupted treatment (OR, 11.6; 95% CI, 8.94-15.1), and treatment failure with prior history of treatment failure (OR, 17.1; 95% CI, 6.97-41.6). Multidrug resistance was strongly associated with adverse treatment outcomes (OR, 10.8; 95% CI, 8.02-14.6). Age > 65 years, male sex, being born abroad, and history of treatment failure were found to be risk factors for adverse treatment outcomes. Hence, patients with any of these characteristics should be carefully monitored and treated aggressively.

  9. Performance characteristics of the new Abbott Real Time MTB assay for detection of Mycobacterium tuberculosis complex in respiratory specimens.

    PubMed

    Vinuesa, Víctor; Navarro, David; Poujois, Sandrine; Zaragoza, Susana; Borrás, Rafael

    2016-03-01

    The performance of the Abbott Real Time MTB assay for detection of Mycobacterium tuberculosis complex in respiratory specimens was evaluated using a standard culture as the reference. The overall concordance between both methods was 0.95. The assay displayed an excellent sensitivity (100% for smear-positive/92.3% for smear-negative specimens) and specificity (100%).

  10. Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens.

    PubMed

    Marlowe, Elizabeth M; Novak-Weekley, Susan M; Cumpio, Joven; Sharp, Susan E; Momeny, Michelle A; Babst, Anna; Carlson, Jonathan S; Kawamura, Masae; Pandori, Mark

    2011-04-01

    A total of 217 specimens submitted for routine smear and culture from three different sites within the western United States were used to evaluate the GeneXpert MTB/RIF assay (for research use only) (Cepheid, Sunnyvale, CA). Overall agreement compared to culture was 89% (98% for smear positives and 72% for smear negatives) for detection of Mycobacterium tuberculosis. PMID:21289151

  11. Clofazimine Contributes Sustained Antimicrobial Activity after Treatment Cessation in a Mouse Model of Tuberculosis Chemotherapy

    PubMed Central

    Swanson, Rosemary V.; Ammerman, Nicole C.; Ngcobo, Bongani; Adamson, John; Moodley, Chivonne; Dorasamy, Afton; Moodley, Sashen; Mgaga, Zinhle; Bester, Linda A.; Singh, Sanil D.; Almeida, Deepak V.

    2016-01-01

    Experimental and clinical studies have indicated that the antileprosy drug clofazimine may contribute treatment-shortening activity when included in tuberculosis treatment regimens. Clofazimine accumulates to high levels in tissues, has a long half-life, and remains in the body for months after administration is stopped. We hypothesized that in tuberculosis treatment, accumulated clofazimine may contribute sustained antimicrobial activity after treatment cessation, and we used the BALB/c mouse model of chronic tuberculosis chemotherapy to address this hypothesis. Mycobacterium tuberculosis-infected mice were treated for 4 weeks or 8 weeks with either isoniazid alone, clofazimine alone, the first-line regimen rifampin-isoniazid-pyrazinamide-ethambutol, or a first-line regimen where clofazimine was administered in place of ethambutol. To evaluate posttreatment antimicrobial activity, bacterial regrowth in the lungs and spleens was assessed at the day of treatment cessation and 2, 4, 6, and 8 weeks after treatment was stopped. Bacterial regrowth was delayed in all mice receiving clofazimine, either alone or in combination, compared to the mice that did not receive clofazimine. This effect was especially evident in mice receiving multidrug therapy. In mice not receiving clofazimine, bacterial regrowth began almost immediately after treatment was stopped, while in mice receiving clofazimine, bacterial regrowth was delayed for up to 6 weeks, with the duration of sustained antimicrobial activity being positively associated with the time that serum clofazimine levels remained at or above the 0.25-μg/ml MIC for M. tuberculosis. Thus, sustained activity of clofazimine may be important in the treatment-shortening effect associated with this drug. PMID:26926638

  12. Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste

    PubMed Central

    Martins, Nelson; Morris, Peter

    2009-01-01

    Objective To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Design Parallel group randomised controlled trial. Setting Three primary care clinics in Dili, Timor-Leste. Participants 270 adults aged ≥18 with previously untreated newly diagnosed pulmonary tuberculosis. Main outcome measures Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Results Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Conclusion Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Trial registration Clinical Trials NCT0019256. PMID:19858174

  13. Treatment Outcomes of Patients Placed on Treatment Under Directly Observed Therapy Short-Course (Dots)

    PubMed Central

    Kaur, Gurpreet; Goel, N.K.; Kumar, Dinesh; Janmeja, A.K.; Swami, H.M.; Kalia, Meenu

    2008-01-01

    Background: Tuberculosis continues to be a pressing health problem in India. The Revised National Tuberculosis Programme (RNTCP), an application of Directly Observed Treatment Short-course (DOTS) in India, launched in 1997 needs continuous evaluation. Objective: To study the outcomes of treatment among the patients put on DOTS under RNTCP in Chandigarh, UT. Material & Methods: A Longitudinal study was conducted during 2004-2005 in 13 Microscopic centres (MC's) spread over 2 Tuberculosis Units (TU's) under District Tuberculosis Centre (DTC) in Union Territory (UT), Chandigarh. A sample of 265 respondents, selected by two-stage stratified random sampling technique, was recruited in the study cohort. Data analysis was done using SPSS-10 statistical software package. Results: For Category I and Category II patients, the Success rate was 98.6% and 90.4% respectively. The overall default rate was 1.1% and failure rate was 2.6%. For re-treatment cases, failure rate was higher i.e. 5.8%. The sputum conversion rate among the new smear positive cases was 93.8% at 3 months of treatment. For the re-treatment cases, spu-tum conversion rate at 3 months was 94.1%. Conclusion: The study concludes that RNTCP is running successfully in UT Chandigarh, having high success rate and low default rate. The reasons for high failure rate should be explored in depth. PMID:20165654

  14. Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB.

    PubMed

    Luetkemeyer, Anne F; Kendall, Michelle A; Wu, Xingye; Lourenço, Maria Cristina; Jentsch, Ute; Swindells, Susan; Qasba, Sarojini S; Sanchez, Jorge; Havlir, Diane V; Grinsztejn, Beatriz; Sanne, Ian M; Firnhaber, Cynthia

    2014-04-01

    Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with <7 days of TB treatment had 1 sputum specimen tested with Direct LPA, MTBDR-Plus LPA, smear microscopy, MGIT, biochemical identification of mycobacterial species, and culture-based drug-susceptibility testing (DST). Of 639 participants, 59.3% were MGIT M. tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

  15. Inoculation site leprosy in a tattoo as a paradoxical reaction following tuberculosis treatment.

    PubMed

    Branagan, P; Moran, B; Fitzgibbon, M; Reid, V; McMenamin, M; Kane, M; Kelly, F; Barnes, L; McLaughlin, A; Keane, J

    2016-05-01

    We present a patient who developed inoculation site leprosy in a tattoo, which was confirmed by Mycobacterium leprae DNA sequencing of a polymerase chain reaction product from a skin biopsy. His leprosy became manifest as a paradoxical reaction only after 8 weeks of treatment for pulmonary tuberculosis. PMID:27084829

  16. In silico evaluation and exploration of antibiotic tuberculosis treatment regimens

    SciTech Connect

    Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; Kirschner, Denise E.

    2015-11-14

    Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data from non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment. In conclusion, our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.

  17. [Use of alpha-tocopherol acetate in the treatment of hemodynamic disorders in patients with pulmonary tuberculosis].

    PubMed

    Ditiatkov, A E; Tikhonov, V A; Radzevich, A E; Zholnin, P A

    2005-01-01

    Examination of 101 patients with pulmonary tuberculosis established the impact of specific intoxication on central hemodynamics in 51 patients. Specific treatment was found to have a certain positive effect on impaired hemodynamics. However, there were no significant changes in patients with severe tuberculosis. Hemodynamics substantially improved when alpha-tocopherol acetate was supplemented to antibacterial therapy.

  18. Multidrug-Resistant Tuberculosis in Patients for Whom First-Line Treatment Failed, Mongolia, 2010–2011

    PubMed Central

    Korver, Sarah; Batbayar, Ochirbat; Nyamdulam, Batiargal; Oyuntsetseg, Sodnomdarjaa; Tsolmon, Bold; Surmaajav, Bazarragchaa; Bayarjargal, Byambaa; Marais, Ben J.

    2015-01-01

    In Ulaanbaatar, Mongolia, multidrug-resistant tuberculosis (MDR TB) was diagnosed for more than a third of new sputum smear–positive tuberculosis patients for whom treatment had failed. This finding suggests a significant risk for community-acquired MDR TB and a need to make rapid molecular drug susceptibility testing available to more people. PMID:26196504

  19. Bedaquiline: A Novel Antitubercular Agent for the Treatment of Multidrug-Resistant Tuberculosis.

    PubMed

    Yadav, Sankalp; Rawal, Gautam; Baxi, Mudit

    2016-08-01

    The developing countries are having an abruptly growing number of drug resistant tuberculosis cases. Multidrug-resistant tuberculosis (MDR-TB) is a type of TB in which the strain of Mycobacterium tuberculosis is resistant to at least Isoniazid and Rifampicin, the two most effective of the four first-line TB drugs (the other two drugs being Ethambutol and Pyrazinamide). The management of such cases is complex and requires a treatment for 24-27 months. The current guidelines available for the management of this type of TB are largely based on the second line TB drugs which are relatively costly, less efficacious and are associated with greater side-effects. The introduction of newer drugs to cater to the high mortality and early sputum culture conversion in the MDR-TB cases is an absolute essential. In the present article, the authors discuss about the introduction of a newer drug named Bedaquiline for the control of MDR-TB. PMID:27656462

  20. Mobile phone text messaging for promoting adherence to anti-tuberculosis treatment: a systematic review

    PubMed Central

    2013-01-01

    Background Mobile phone text messaging (SMS) has the potential to promote adherence to tuberculosis treatment. This systematic review aims to synthesize current evidence on the effectiveness of SMS interventions in improving patients’ adherence to tuberculosis treatment. Methods We searched electronic databases (PubMed, EMBASE, Science Citation Index), reference lists of relevant articles, conference proceedings, and selected websites for eligible studies available by 15 February 2013; regardless of language or publication status. Two authors independently screened selected eligible studies, and assessed risk of bias in included studies; resolving discrepancies by discussion and consensus. Results We identified four studies that compared the outcomes of the SMS intervention group with controls. Only one of the four studies was a randomized controlled trial. This was conducted in Argentina and the SMS intervention did not significantly improve adherence to tuberculosis treatment compared to self-administration of tuberculosis treatment (risk ratio [RR] 1.49, 95% confidence intervals [CI] 0.90 to 2.42). One of the non-randomized studies, conducted in South Africa, which compared SMS reminders to directly observed therapy short course (DOTS) reported similar rates of tuberculosis cure (62.35% vs. 66.4%) and treatment success (72.94% vs. 69.4%). A second study from South Africa, utilized SMS reminders when patients delayed in opening their pill bottles and reported increased tuberculosis cure (RR 2.32, 95% CI 1.60 to 3.36) and smear conversion (RR 1.62, 95% CI 1.09 to 2.42) rates compared to DOTS. In the third non-randomized study, conducted in Kenya, use of SMS reminders increased rates of clinic attendance on scheduled days compared to standard care (RR 1.56, 95% CI 1.06 to 2.29). Using the GRADE approach, we rate the quality of the evidence as low, mainly because of the high risk of bias and heterogeneity of effects across studies. Conclusions This systematic

  1. [Interdepartmental interaction in the detection and treatment of patients with tuberculosis].

    PubMed

    Smerdin, S V; Chernov, M T; Kopylova, I F; Babichuk, L D

    2007-01-01

    The experience of interdepartmental interaction in solving the problem of tuberculosis in the Kemerovo Region has been analyzed. The region's administration has strengthened the material-and-technical basis of the service. The advisory tuberculosis council has been set up. Territorial interdepartmental commissions have been organized. The level of an intervention with the general medical network (GMN) has been increased. A qualitative sputum test has been carried out for acid-resistant mycobacteria. The Main Board of the Federal Penal Jurisdiction Service (MBFPJS) and the Board of Internal Affairs are attracted to examine social risk-group persons. Strictly uncontrolled chemotherapy for patients with tuberculosis has been introduced on the basis of GMN at the stage of aftercare and by the forces of the Red Cross Committee. Along with the MBFPJS, continuity has been established in the treatment of patients with tuberculosis. Juridical attraction of bacteria-isolating person to treatment has been introduced. The work done has substantially improved the detection and treatment of patients, but there are problems to be solved.

  2. Vitamin D, vitamin D receptor, and cathelicidin in the treatment of tuberculosis.

    PubMed

    Selvaraj, P

    2011-01-01

    Vitamin D plays a major role in bone mineral density and calcium homeostasis. Apart from its classical action, the active form of vitamin D [1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))] influences the innate and adaptive immune functions through vitamin D receptor (VDR) that are present in various cells of the immune system. Vitamin D deficiencies have been associated with development of tuberculosis (TB) disease, caused by Mycobacterium tuberculosis. Vitamin D(3) is shown to enhance macrophage phagocytosis of M. tuberculosis and increases the production of antimicrobial peptide cathelicidin and killing of M. tuberculosis. During the preantibiotic era, exposure to sunlight and supplementation of vitamin D were the methods of choice for treatment of TB. Vitamin D supplementation showed sputum clearance and radiological improvement and reduction in mortality among human immunodeficiency virus (HIV)-infected patients with TB. VDR gene polymorphisms regulate the immunomodulatory effect of vitamin D(3) and are associated with faster sputum conversion during anti-TB treatment. The emerging evidences regarding immunomodulatory properties of vitamin D(3) have rekindled interest in vitamin D as an adjunct to anti-TB therapy. The current review explains the important potential application of vitamin D in enhancing the innate immunity to TB and the role of VDR gene variants on anti-TB treatment.

  3. A concurrent comparison of home and sanatorium treatment of pulmonary tuberculosis in South India

    PubMed Central

    1959-01-01

    In India, as in most under-development countries, the tuberculosis problem is aggravated by an acute shortage of sanatorium beds. The number of active cases of tuberculosis in the country has been estimated at 2 ½ million, but only 23 000 tuberculosis beds are available. In these circumstances great importance attaches to the possibility of applying mass domiciliary chemotherapy as a substitute for sanatorium treatment in cases of pulmonary tuberculosis. The findings of the present study, based on a comparison of the two types of treatment over a period of 12 months, show that despite the manifest advantages of sanatorium care—rest, adequate diet, nursing and supervised medicine-taking—the merits of domiciliary chemotherapy are comparable to those of sanatorium treatment, and that it would therefore be appropriate to treat the majority of patients at home, provided an adequate service were established. Imagesp135-ap136-ap137-ap138-ap139-ap140-ap141-ap142-ap143-ap144-a PMID:20604054

  4. Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes

    PubMed Central

    Jiménez-Corona, María Eugenia; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

    2013-01-01

    Objective To determine the clinical consequences of pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM). Methods We conducted a prospective study of patients with TB in Southern Mexico. From 1995 to 2010, patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. Annual follow-ups were performed to ascertain treatment outcome, recurrence, relapse and reinfection. Results The prevalence of DM among 1262 patients with pulmonary TB was 29.63% (n=374). Patients with DM and pulmonary TB had more severe clinical manifestations (cavities of any size on the chest x-ray, adjusted OR (aOR) 1.80, 95% CI 1.35 to 2.41), delayed sputum conversion (aOR 1.51, 95% CI 1.09 to 2.10), a higher probability of treatment failure (aOR 2.93, 95% CI 1.18 to 7.23), recurrence (adjusted HR (aHR) 1.76, 95% CI 1.11 to 2.79) and relapse (aHR 1.83, 95% CI 1.04 to 3.23). Most of the second episodes among patients with DM were caused by bacteria with the same genotype but, in 5/26 instances (19.23%), reinfection with a different strain occurred. Conclusions Given the growing epidemic of DM worldwide, it is necessary to add DM prevention and control strategies to TB control programmes and vice versa and to evaluate their effectiveness. The concurrence of both diseases potentially carries a risk of global spreading, with serious implications for TB control and the achievement of the United Nations Millennium Development Goals. PMID:23250998

  5. [TUBERCULOSIS ANNUAL REPORT 2014--(1) Summary of Statistics on Tuberculosis Notification and Foreign-born Tuberculosis Patients].

    PubMed

    2016-02-01

    This brief is the first of a series of documents based on the Tuberculosis Annual Report 2014. It includes a summary of tuberculosis (TB) statistics, including data on foreign-born TB patients notified and registered in Japan in 2014. For the first time, the number of newly notified cases (all forms of TB) fell below 20,000. In 2014, a total of 19,615 patients were notified, a rate of 15.4 per 100,000 population The number of sputum-smear positive pulmonary. TB patients notified was 7,651, a rate of 6.0 per 100,000 population. The number of patients with latent TB infections increased slightly from 7,147 in 2013 to 7,562 in 2014. The proportion of miliary TB cases has constantly increased over the past 10 years, especially among women aged 80 years and older. The number of foreign-born TB patients continued to increase from 1,064 in 2013 to 1,101 in 2014. In 2014, new foreign-born TB patients aged 20-29 years accounted for 44.1% of all new TB patients in that age group. Among foreign-born TB patients, half were from the Philippines (26.5%) and China (23.5%). However, the number of patients from Vietnam and Nepal is increasing. Among foreign-born TB patients, 28% were regular employees, 26% were students, and 20% were unemployed. The changing trend in the nationality of foreign students entering Japan may at least partially explain the differences in TB burden among foreign-born patients, by country of birth. As we expect to see the proportion of foreign-born TB patients continue to rise, more tailored case identification and treatment support activities are needed.

  6. [TUBERCULOSIS ANNUAL REPORT 2014--(1) Summary of Statistics on Tuberculosis Notification and Foreign-born Tuberculosis Patients].

    PubMed

    2016-02-01

    This brief is the first of a series of documents based on the Tuberculosis Annual Report 2014. It includes a summary of tuberculosis (TB) statistics, including data on foreign-born TB patients notified and registered in Japan in 2014. For the first time, the number of newly notified cases (all forms of TB) fell below 20,000. In 2014, a total of 19,615 patients were notified, a rate of 15.4 per 100,000 population The number of sputum-smear positive pulmonary. TB patients notified was 7,651, a rate of 6.0 per 100,000 population. The number of patients with latent TB infections increased slightly from 7,147 in 2013 to 7,562 in 2014. The proportion of miliary TB cases has constantly increased over the past 10 years, especially among women aged 80 years and older. The number of foreign-born TB patients continued to increase from 1,064 in 2013 to 1,101 in 2014. In 2014, new foreign-born TB patients aged 20-29 years accounted for 44.1% of all new TB patients in that age group. Among foreign-born TB patients, half were from the Philippines (26.5%) and China (23.5%). However, the number of patients from Vietnam and Nepal is increasing. Among foreign-born TB patients, 28% were regular employees, 26% were students, and 20% were unemployed. The changing trend in the nationality of foreign students entering Japan may at least partially explain the differences in TB burden among foreign-born patients, by country of birth. As we expect to see the proportion of foreign-born TB patients continue to rise, more tailored case identification and treatment support activities are needed. PMID:27263231

  7. Tuberculosis in an Indochinese refugee camp: epidemiology, management and therapeutic results.

    PubMed

    Rieder, H L

    1985-09-01

    In a 3-year period tuberculosis was diagnosed in 629 patients in Thailand's largest camp for Kampuchean refugees: 62% had pulmonary disease and 38% extrapulmonary forms. Tuberculosis of lymph nodes was the most important extrapulmonary manifestation (50%). The mean annual notification rates were 0.5% and 0.24% for all forms and smear-positive pulmonary tuberculosis respectively. There was a steep rise in the annual notification rate with increasing age. A 6-month course of fully supervised chemotherapy efficiently counteracted defaulting, early absconding and initial drug resistance. Seventy-three per cent of all patients remained on chemotherapy for the planned period; only 2% of the smear-positive patients failed bacteriologically on chemotherapy. Of the patients with the most common forms of extrapulmonary disease, 90% showed a favourable response to chemotherapy.

  8. Serum PCT and its Relation to Body Weight Gain in Pulmonary Tuberculosis.

    PubMed

    Rohini, K; Bhat, Surekha; Srikumar, P S; Mahesh Kumar, A

    2015-07-01

    The present study was aimed at assessing alterations in serum PCT in terms of its relation to body weight gain in pulmonary tuberculosis (PTB) patients undergoing treatment. Among patients (25-75 years) diagnosed with pulmonary tuberculosis, those that were new smear positive, showed sputum conversion at the end of 2 months and were declared clinically cured at the end of 6 months, were included in the study (n = 40). Serum procalcitonin was determined by BRAHMS PCT-Q kit. Patients were divided into two study groups-Group 1 (n = 21; serum PCT > 2 ng/ml at diagnosis), Group 2 (n = 19; serum PCT > 10 ng/ml at diagnosis). Body weights of all patients were obtained at three different time points, PTB-0 (at diagnosis), PTB-2 (after 2 months of intensive treatment) and PTB-6 (after 6 months of treatment). In both groups, mean body weights at PTB-2 and PTB-6 were significantly higher than those at PTB-0 and at PTB-6 were significantly higher than those at PTB-2. However, percentage body weight gain following 2 months of intensive treatment was higher in group 1 (4.05 % gain, p < 0.01) than in group 2 (2.75 % body weight gain, p < 0.05). Thus, the percentage gain in group 1 was tending more towards the desirable minimum gain of 5 % during intensive phase. Increase in serum PCT levels in pulmonary tuberculosis is inversely associated with body weight gain during treatment. Thus, PCT could play a role in regulation of body weight gain in anorectic conditions like tuberculosis.

  9. Announcement: Clinical Practice Guidelines Published for Treatment of Drug-Susceptible Tuberculosis.

    PubMed

    2016-01-01

    The American Thoracic Society, CDC, and the Infectious Diseases Society of America (IDSA) have jointly sponsored the development of guidelines for the treatment of drug-susceptible tuberculosis, which were published by IDSA in Clinical Infectious Diseases on August 11, 2016 (1) and are available through IDSA (http://www.idsociety.org/Index.aspx) and CDC (http://www.cdc.gov/tb/publications/guidelines/treatment.htm). PMID:27537009

  10. Staged treatment of thoracic and lumbar spinal tuberculosis with flow injection abscess.

    PubMed

    Zeng, Hao; Zhang, Yupeng; Shen, Xiongjie; Luo, Chengke; Xu, Zhengquan; Liu, Zheng; Liu, Xiangyang; Wang, Xiyang

    2015-01-01

    The study was to investigate the feasibility and effectiveness of posterior-only approach combining with puncture drainage under CT-guide in staged treatment of thoracic and lumbar spinal tuberculosis with flow injection abscess. We retrospectively analyzed 15 patients (came from 72 cases with thoracic and lumbar spinal tuberculosis) with flow injection abscesses underwent surgery from January 2007 to February 2009, and evaluated the American Spinal Injury Association (ASIA) scoring system of nerve function, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), abscess absorption time and the Oswestry Disability Index (ODI), preoperatively and postoperatively. 15 patients were followed up for 13-37 months, no recurrence of tuberculosis, no fixation loosening and neurologic symptoms aggravated. The flow injection abscesses are absorbed within 3-6 months postoperative operation. In final follow-up, ESR went down to 5.2±2.1 mm/h from preoperative 79.6±14.8 mm/h, CRP decreased from preoperative 49.3±7.5 mg/L to 1.8±0.7 mg/L, ODI changed from 75.13±20.15 to 16.72±8.62, all of them changed significantly (P<0.05). In conclusions, one-stage posterior debridement, interbody fusion, pedicle screw fixation and two-stage CT-guided interventional therapy were safe and effective in treatment of the thoracic and lumbar spinal tuberculosis with flow injection abscess. PMID:26770442

  11. Staged treatment of thoracic and lumbar spinal tuberculosis with flow injection abscess

    PubMed Central

    Zeng, Hao; Zhang, Yupeng; Shen, Xiongjie; Luo, Chengke; Xu, Zhengquan; Liu, Zheng; Liu, Xiangyang; Wang, Xiyang

    2015-01-01

    The study was to investigate the feasibility and effectiveness of posterior-only approach combining with puncture drainage under CT-guide in staged treatment of thoracic and lumbar spinal tuberculosis with flow injection abscess. We retrospectively analyzed 15 patients (came from 72 cases with thoracic and lumbar spinal tuberculosis) with flow injection abscesses underwent surgery from January 2007 to February 2009, and evaluated the American Spinal Injury Association (ASIA) scoring system of nerve function, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), abscess absorption time and the Oswestry Disability Index (ODI), preoperatively and postoperatively. 15 patients were followed up for 13-37 months, no recurrence of tuberculosis, no fixation loosening and neurologic symptoms aggravated. The flow injection abscesses are absorbed within 3-6 months postoperative operation. In final follow-up, ESR went down to 5.2±2.1 mm/h from preoperative 79.6±14.8 mm/h, CRP decreased from preoperative 49.3±7.5 mg/L to 1.8±0.7 mg/L, ODI changed from 75.13±20.15 to 16.72±8.62, all of them changed significantly (P<0.05). In conclusions, one-stage posterior debridement, interbody fusion, pedicle screw fixation and two-stage CT-guided interventional therapy were safe and effective in treatment of the thoracic and lumbar spinal tuberculosis with flow injection abscess. PMID:26770442

  12. Pharmacokinetics of Efavirenz and Treatment of HIV-1 Among Pregnant Women With and Without Tuberculosis Coinfection

    PubMed Central

    Dooley, Kelly E.; Denti, Paolo; Martinson, Neil; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer; Haas, David W.; Hull, Jennifer; Msandiwa, Regina; Castel, Sandra; Wiesner, Lubbe; Chaisson, Richard E.; McIlleron, Helen

    2015-01-01

    Background Pregnancy and tuberculosis treatment or prophylaxis can affect efavirenz pharmacokinetics, maternal human immunodeficiency virus type 1 (HIV-1) treatment outcomes, and mother-to-child transmission (MTCT) risk. Methods We evaluated a prospective cohort of pregnant, HIV-infected women with and without tuberculosis in Soweto, South Africa. Pharmacokinetic sampling was performed at gestation week 37 and during the postpartum period. Efavirenz trough concentrations (Cmin) were predicted using population pharmacokinetic models. HIV-viral load was measured at delivery for mothers and at 6 weeks of age for infants. Results Ninety-seven women participated; 44 had tuberculosis. Median efavirenz Cmin during pregnancy was 1.35 µg/mL (interquartile range [IQR], 0.90–2.07 µg/mL; 27% had an efavirenz Cmin of < 1 µg/mL), compared with a median postpartum value of 2.00 µg/mL (IQR, 1.40–3.59 µg/mL; 13% had an efavirenz Cmin of < 1 µg/mL). A total of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz Cmin of <1 µg/mL. Rifampin did not reduce the efavirenz Cmin. Isoniazid (for prophylaxis or treatment), though, reduced the rate of efavirenz clearance. At delivery, median durations of ART were 13 weeks (IQR, 9–18 weeks) and 21 weeks (IQR, 13–64 weeks) for women with and those without tuberculosis, respectively; 55% and 83%, respectively, had a viral load of <20 copies/mL (P = .021). There was 1 case of MTCT. Conclusions Pregnancy increased the risk of low efavirenz concentrations, but MTCT was rare. A detectable HIV-viral load at delivery was more common among pregnant women with tuberculosis, in whom ART was generally initiated later. PMID:25081933

  13. A Comparative Study of Induced Sputum and Bronchial Washings in Diagnosing Sputum Smear Negative Pulmonary Tuberculosis

    PubMed Central

    Mandava, Venu; Namballa, Usha Rani; Makala, Sravani

    2016-01-01

    Introduction Tuberculosis is one of the most important public health problem worldwide. Detecting patients with active pulmonary Koch’s disease is an important component of tuberculosis control programs. However, at times in patients even with a compatible clinical picture, sputum smears do not reveal acid-fast bacilli and smear-negative pulmonary tuberculosis remains a common problem. Aim The present study is aimed to compare the results of induced sputum and bronchial washings smear in patients suspected to have sputum smear negative pulmonary tuberculosis. Materials and Methods A prospective study conducted from August 2014 to July 2015, comprising 120 patients fulfilling study criteria. Patients with respiratory symptoms and chest roentgenogram suspicious of pulmonary tuberculosis with no previous history of anti-tuberculosis treatment and two spontaneous sputum smear samples negative for acid fast bacilli were included. Patients with active haemoptysis and sputum positive were excluded from the study. Sputum induction was done by using 5-10 ml of 3% hypertonic saline through ultrasonic nebulizer taking safety precautions. All the patient underwent fibreoptic bronchoscopy after six hours fasting on the same day. About 20 ml of normal saline instilled into the suspected pathology area and washings were taken with gentle suction. The sample processing and fluorescent staining for acid fast bacilli was done in a designated microscopy lab. Results Out of 120 sputum smear negative pulmonary tuberculosis patients, induced sputum smear examination detected acid fast bacilli in 76 patients (63.3%) and acid fast bacilli detected from bronchial washings in 94 patients (78.3%). Smear positivity was higher in cavitary and infiltrative lesions as compared to consolidation and infrahilar pattern disease. Conclusion Even though both induced sputum and bronchial washings procedures were valuable for the diagnosis of sputum smear negative, sputum induction with hypertonic

  14. Using animal models to develop new treatments for tuberculosis.

    PubMed

    Nuermberger, Eric

    2008-10-01

    Animal models have an important role in the preclinical evaluation of new antituberculosis drug candidates. Although it does not recapitulate the clinicopathological manifestations of tuberculosis in humans, the mouse remains the best characterized and most economical animal model for experimental chemotherapy. Provided care is taken to optimize the experimental conditions, the mouse has produced reliable data on the bactericidal and sterilizing activity of existing antituberculosis drugs and informed numerous clinical trials. Still, other animal models, especially the guinea pig, may have utility as confirmatory, or even alternative, models under certain circumstances. This chapter reviews some of the important considerations when selecting an animal model and presents a model for the sequential evaluation of a new compound with promising antituberculosis activity.

  15. Efficacy and effect of free treatment on multidrug-resistant tuberculosis

    PubMed Central

    ZHANG, QING; WU, ZHEYUAN; ZHANG, ZURONG; SHA, WEI; SHEN, XIN; XIAO, HEPING

    2016-01-01

    Multidrug-resistant tuberculosis (MDR-TB) is a serious public health and social issue. It pertains to the type of tuberculosis that is resistant simultaneously to isoniazid and rifampicin. MDR-TB has a high mortality and is expensive to treat. The aim of the present study was to examine the therapeutic effects of individualized free treatment and the relevant influencing factors on the treatment outcome for MDR-TB. A prospective study module was used to analyze the therapeutic outcome of MDR-TB with individualized free treatment for 160 patients between 2011 and 2014. Statistical analysis was performed using the Chi-square or Fisher's exact test, and the odds ratio was calculated using a logistic regression analysis model. In total, 160 patients were enrolled in the study for treatment of MDR-TB. From these, 88 cases completed the course of treatment, and 70 cases were successfully treated. Of the remaining 72 cases, 37 cases exhibited treatment failure, 18 cases were suspended during treatment and 17 patients succumbed to the disease. The results showed that the confounding factors were: i) retreatment (p<0.05); ii) occurrence of diabetes (p<0.001); iii) lesion without improvement in radiography during treatment (p=0.001); iv) positive sputum culture for Mycobacterium tuberculosis after 3-month treatment (p<0.05); and v) termination of treatment due to adverse reaction (p<0.05). These factors were associated with poor treatment outcomes by logistic regression analysis. Adverse drug reaction was observed in 33 cases and treatment was terminated or changed permanently in 29 of these cases. The most common adverse reaction was liver function damage caused by pyrazinamide and leucopenia caused by rifabutin. One patient suffered from serious liver failure. In conclusion, the success rate of long treatment course for MDR-TB is not high due to many adverse reactions. Occurrence of diabetes is the main factor that caused poor efficacy. PMID:26997992

  16. New agents for the treatment of drug-resistant Mycobacterium tuberculosis.

    PubMed

    Hoagland, Daniel T; Liu, Jiuyu; Lee, Robin B; Lee, Richard E

    2016-07-01

    Inadequate dosing and incomplete treatment regimens, coupled with the ability of the tuberculosis bacilli to cause latent infections that are tolerant of currently used drugs, have fueled the rise of multidrug-resistant tuberculosis (MDR-TB). Treatment of MDR-TB infections is a major clinical challenge that has few viable or effective solutions; therefore patients face a poor prognosis and years of treatment. This review focuses on emerging drug classes that have the potential for treating MDR-TB and highlights their particular strengths as leads including their mode of action, in vivo efficacy, and key medicinal chemistry properties. Examples include the newly approved drugs bedaquiline and delaminid, and other agents in clinical and late preclinical development pipeline for the treatment of MDR-TB. Herein, we discuss the challenges to developing drugs to treat tuberculosis and how the field has adapted to these difficulties, with an emphasis on drug discovery approaches that might produce more effective agents and treatment regimens. PMID:27151308

  17. Cytokine Response to Antigen Stimulation of Whole Blood from Patients with Mycobacterium ulcerans Disease Compared to That from Patients with Tuberculosis

    PubMed Central

    Phillips, R.; Horsfield, C.; Kuijper, S.; Sarfo, S. F.; Obeng-Baah, J.; Etuaful, S.; Nyamekye, B.; Awuah, P.; Nyarko, K. M.; Osei-Sarpong, F.; Lucas, S.; Kolk, A. H. J.; Wansbrough-Jones, M.

    2006-01-01

    Mycobacterium ulcerans disease (Buruli ulcer) is a skin-ulcerating infection common in some parts of the tropics. We have investigated cytokine secretion after stimulation of whole blood from Buruli ulcer (BU) patients in a region of endemicity in Ghana with M. ulcerans sonicate or culture filtrate antigens to investigate the development of the response over time and its specificity by comparison with the response to Mycobacterium tuberculosis sonicate in human immunodeficiency virus-negative tuberculosis patients. Significant gamma interferon (IFN-γ) production in response to whole-blood stimulation with M. ulcerans sonicate was detected in patients with ulcers, which was higher than that in patients with nodules but similar to subjects with healed BU. The mean IFN-γ response in household contacts of BU patients was not significantly different from that in healthy control subjects from an area of nonendemicity. Results in patients with untreated, smear-positive pulmonary tuberculosis and tuberculosis patients on treatment for more than 2 weeks showed that BU patients responded better to M. ulcerans antigens than tuberculosis patients. In contrast, interleukin-10 results were higher in patients with active M. ulcerans disease than in those with healed lesions, but the pattern of response was similar to that seen in tuberculosis. A similar pattern of cytokine secretion was found using M. tuberculosis sonicate as an antigen. Neither of the two culture filtrate antigens of M. ulcerans appeared to be more specific than M. ulcerans sonicate. In the early stages of M. ulcerans disease there was a mixed Th1 and Th2 cytokine response, but the Th1 response emerged as the dominant type. PMID:16467334

  18. Psychiatric Morbidity and Other Factors Affecting Treatment Adherence in Pulmonary Tuberculosis Patients

    PubMed Central

    Pachi, Argiro; Bratis, Dionisios; Moussas, Georgios; Tselebis, Athanasios

    2013-01-01

    As the overall prevalence of TB remains high among certain population groups, there is growing awareness of psychiatric comorbidity, especially depression and its role in the outcome of the disease. The paper attempts a holistic approach to the effects of psychiatric comorbidity to the natural history of tuberculosis. In order to investigate factors associated with medication nonadherence among patients suffering from tuberculosis, with emphasis on psychopathology as a major barrier to treatment adherence, we performed a systematic review of the literature on epidemiological data and past medical reviews from an historical perspective, followed by theoretical considerations upon the relationship between psychiatric disorders and tuberculosis. Studies reporting high prevalence rates of psychiatric comorbidity, especially depression, as well as specific psychological reactions and disease perceptions and reviews indicating psychiatric complications as adverse effects of anti-TB medication were included. In sum, data concerning factors affecting medication nonadherence among TB patients suggested that better management of comorbid conditions, especially depression, could improve the adherence rates, serving as a framework for the effective control of tuberculosis, but further studies are necessary to identify the optimal way to address such issues among these patients. PMID:23691305

  19. Tuberculosis treatment outcomes and socio-economic status: a prospective study in Duque de Caxias, Brazil.

    PubMed

    Belo, M T C T; Luiz, R R; Teixeira, E G; Hanson, C; Trajman, A

    2011-07-01

    A prospective study was conducted to evaluate tuberculosis treatment outcomes according to socio-economic status (SES) using different classification criteria. Patients aged ≥18 years under treatment for ≤8 weeks were interviewed. Outcomes were classified as successful (cure/completed) or unsuccessful (default/failure/death). The overall treatment default ratio was 20.9% and the unsuccessful outcome rate was 24.1%. Unsuccessful treatment was associated with SES according to any criteria used, except for the definition of poverty line. Poverty seems to be hampering the achievement of the World Health Organization targeted 90% cure rate in developing settings.

  20. Factors Associated with Unfavorable Treatment Outcomes in New and Previously Treated TB Patients in Uzbekistan: A Five Year Countrywide Study

    PubMed Central

    Gadoev, Jamshid; Asadov, Damin; Tillashaykhov, Mirzagolib; Tayler-Smith, Katie; Isaakidis, Petros; Dadu, Andrei; de Colombani, Pierpaolo; Gudmund Hinderaker, Sven; Parpieva, Nargiza; Ulmasova, Dilrabo; Jalolov, Avazbek; Hamraev, Atadjan; Ali, Engy; van den Boom, Martin; Hammerich, Asmus; Gozalov, Ogtay; Dara, Masoud

    2015-01-01

    Background TB is one of the main health priorities in Uzbekistan and relatively high rates of unfavorable treatment outcomes have recently been reported. This requires closer analysis to explain the reasons and recommend interventions to improve the situation. Thus, by using countrywide data this study sought to determine trends in unfavorable outcomes (lost-to-follow-ups, deaths and treatment failures) and describe their associations with socio-demographic and clinical factors. Method A countrywide retrospective cohort study of all new and previously treated TB patients registered in the National Tuberculosis programme between January 2006 and December 2010. Results Among 107,380 registered patients, 67% were adults, with smaller proportions of children (10%), adolescents (4%) and elderly patients (19%). Sixty per cent were male, 66% lived in rural areas, 1% were HIV-infected and 1% had a history of imprisonment. Pulmonary TB (PTB) was present in 77%, of which 43% were smear-positive and 53% were smear-negative. Overall, 83% of patients were successfully treated, 6% died, 6% were lost-to-follow-up, 3% failed treatment and 2% transferred out. Factors associated with death included being above 55 years of age, HIV-positive, sputum smear positive, previously treated, jobless and living in certain provinces. Factors associated with lost-to-follow-up were being male, previously treated, jobless, living in an urban area, and living in certain provinces. Having smear-positive PTB, being an adolescent, being urban population, being HIV-negative, previously treated, jobless and residing in particular provinces were associated with treatment failure. Conclusion Overall, 83% treatment success rate was achieved. However, our study findings highlight the need to improve TB services for certain vulnerable groups and in specific areas of the country. They also emphasize the need to develop unified monitoring and evaluation tools for drug-susceptible and drug-resistant TB, and

  1. The relationship between chitotriosidase activity and tuberculosis.

    PubMed

    Chen, M; Deng, J; Li, W; Su, C; Xia, Y; Wang, M; Li, X; Abuaku, B K; Tan, H; Wen, S W

    2015-11-01

    Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future. PMID:26418349

  2. Global guidelines for treatment of tuberculosis among persons living with HIV: unresolved issues.

    PubMed

    Kumar, A; Kumar, A M V; Gupta, D; Kanchar, A; Mohammed, S; Srinath, S; Tripathy, S; Rajasekaran, S; Chan, P-L; Swaminathan, S; Dewan, P K

    2012-05-01

    The Revised National Tuberculosis Control Programme (RNTCP) in India uses a fully intermittent thrice-weekly rifampicin-containing regimen for all tuberculosis (TB) patients, including those who are human immunodeficiency virus (HIV) infected, whereas the World Health Organization (WHO) recommends daily anti-tuberculosis treatment at least during the intensive phase. The WHO recommendation was based on the results of a meta-analysis demonstrating increased risk of recurrence and failure among HIV-infected TB patients receiving intermittent TB treatment compared to a daily regimen. Review of the primary evidence indicates limited, low-quality information on intermittency, mostly from observational studies in the pre-antiretroviral treatment (ART) era. Molecular epidemiology in India indicates that most of the recurrences and many of the failures result from exogenous re-infection, suggesting poor infection control and high transmission rather than poor regimen efficacy. Subsequently published studies have shown acceptable treatment outcomes among HIV-infected TB patients receiving intermittent anti-tuberculosis regimens with concomitant ART. Treatment outcomes among HIV-infected TB patients treated under programmatic conditions show low failure rates but high case fatality; death has been associated with lack of ART. The highest priority is therefore to reduce mortality by linking all HIV-infected TB patients to ART. While urgently seeking to reduce death rates among HIV-infected TB patients, given the poor evidence for change and operational advantages of an intermittent regimen, the RNTCP intends to collect the necessary evidence to inform national policy decisions through randomised clinical trials. PMID:22507931

  3. Treatment Outcome and Associated Factors among Tuberculosis Patients in Debre Tabor, Northwestern Ethiopia: A Retrospective Study.

    PubMed

    Melese, Addisu; Zeleke, Balew; Ewnete, Biniam

    2016-01-01

    Background. Assessing the outcomes of tuberculosis (TB) treatment is an important indicator for evaluation of the effectiveness of tuberculosis control programs. In Ethiopia, directly observed treatment short course (DOTS) was included in the national tuberculosis control program as a strategy but little is known about its effectiveness in the study area. Therefore, this study was aimed at assessing the treatment outcomes of TB patients and associated factors in Debre Tabor, northwest Ethiopia. Methods. A retrospective study was conducted among TB patients for the period from May 2008 to April 2013 at Debre Tabor Health Center, northwest Ethiopia. Data were entered and analyzed using SPSS version 20.0. Descriptive statistics were used to generate frequency tables and figures. Logistic regressions were used to identify factors associated with treatment outcomes at P value ≤ 0.05. Results. Out of 339 patients (197 males and 142 females) registered for antituberculosis treatment in Debre Tabor Health Center, only 303 patients were included in the treatment outcome analysis and 87.1% had successful treatment outcome while 12.9% had unsuccessful treatment outcome. In the multivariate logistic regression analysis, the odds of successful treatment outcome were higher among patients ≥45 years of age (AOR = 3.807, 95% CI: 1.155-12.544) and lower among females (AOR = 0.347, 95% CI: 0.132-0.917), rural residents (AOR = 0.342, 95% CI: 0.118-0.986), and negative smear result at the second month of treatment (AOR = 0.056, 95% CI: 0.005-0.577) as compared to their counterparts. Conclusion. The treatment outcome of all forms of tuberculosis patients in Debre Tabor health center was satisfactory as expected from effective implementation of DOTS. Although the observed successful treatment outcome was in agreement with the national target, follow-up of patients during the course of treatment to trace the treatment outcomes of transferred-out patients and assessment of other

  4. Treatment Outcome and Associated Factors among Tuberculosis Patients in Debre Tabor, Northwestern Ethiopia: A Retrospective Study

    PubMed Central

    Zeleke, Balew; Ewnete, Biniam

    2016-01-01

    Background. Assessing the outcomes of tuberculosis (TB) treatment is an important indicator for evaluation of the effectiveness of tuberculosis control programs. In Ethiopia, directly observed treatment short course (DOTS) was included in the national tuberculosis control program as a strategy but little is known about its effectiveness in the study area. Therefore, this study was aimed at assessing the treatment outcomes of TB patients and associated factors in Debre Tabor, northwest Ethiopia. Methods. A retrospective study was conducted among TB patients for the period from May 2008 to April 2013 at Debre Tabor Health Center, northwest Ethiopia. Data were entered and analyzed using SPSS version 20.0. Descriptive statistics were used to generate frequency tables and figures. Logistic regressions were used to identify factors associated with treatment outcomes at P value ≤ 0.05. Results. Out of 339 patients (197 males and 142 females) registered for antituberculosis treatment in Debre Tabor Health Center, only 303 patients were included in the treatment outcome analysis and 87.1% had successful treatment outcome while 12.9% had unsuccessful treatment outcome. In the multivariate logistic regression analysis, the odds of successful treatment outcome were higher among patients ≥45 years of age (AOR = 3.807, 95% CI: 1.155–12.544) and lower among females (AOR = 0.347, 95% CI: 0.132–0.917), rural residents (AOR = 0.342, 95% CI: 0.118–0.986), and negative smear result at the second month of treatment (AOR = 0.056, 95% CI: 0.005–0.577) as compared to their counterparts. Conclusion. The treatment outcome of all forms of tuberculosis patients in Debre Tabor health center was satisfactory as expected from effective implementation of DOTS. Although the observed successful treatment outcome was in agreement with the national target, follow-up of patients during the course of treatment to trace the treatment outcomes of transferred-out patients and assessment of

  5. Evaluation of the Speed-oligo Direct Mycobacterium tuberculosis Assay for Molecular Detection of Mycobacteria in Clinical Respiratory Specimens

    PubMed Central

    Lara-Oya, Ana; Mendoza-Lopez, Pablo; Rodriguez-Granger, Javier; Fernández-Sánchez, Ana María; Bermúdez-Ruiz, María Pilar; Toro-Peinado, Inmaculada; Palop-Borrás, Begoña; Navarro-Marí, Jose María

    2013-01-01

    We present the first evaluation of a novel molecular assay, the Speed-oligo Direct Mycobacterium tuberculosis (SO-DMT) assay, which is based on PCR combined with a dipstick for the detection of mycobacteria and the specific identification of M. tuberculosis complex (MTC) in respiratory specimens. A blind evaluation was carried out in two stages: first, under experimental conditions on convenience samples comprising 20 negative specimens, 44 smear- and culture-positive respiratory specimens, and 11 sputa inoculated with various mycobacterium-related organisms; and second, in the routine workflow of 566 fresh respiratory specimens (4.9% acid-fast bacillus [AFB] smear positives, 7.6% MTC positives, and 1.8% nontuberculous mycobacteria [NTM] culture positives) from two Mycobacterium laboratories. SO-DMT assay showed no reactivity in any of the mycobacterium-free specimens or in those with mycobacterium-related organisms. Compared to culture, the sensitivity in the selected smear-positive specimens was 0.91 (0.92 for MTC and 0.90 for NTM), and there was no molecular detection of NTM in a tuberculosis case or vice versa. With respect to culture and clinical data, the sensitivity, specificity, and positive and negative predictive values for the SO-DMT system in routine specimens were 0.76 (0.93 in smear positives [1.0 for MTC and 0.5 for NTM] and 0.56 in smear negatives [0.68 for MTC and 0.16 for NTM]), 0.99, 0.85 (1.00 in smear positives and 0.68 in smear negatives), and 0.97, respectively. Molecular misidentification of NTM cases occurred when testing 2 gastric aspirates from two children with clinically but not microbiologically confirmed lung tuberculosis. The SO-DMT assay appears to be a fast and easy alternative for detecting mycobacteria and differentiating MTC from NTM in smear-positive respiratory specimens. PMID:23100355

  6. [The role of corticotherapy and endoscopy in the treatment of urogenital tuberculosis].

    PubMed

    Bennani, S; Aboutaieb, R; el Mrini, M; Benjelloun, S

    1994-01-01

    Despite the efficacy of new tuberculostatic agents, urogenital tuberculosis still constitutes a threat to renal function due to fibrosis secondary to healing of the lesions. The authors studied the place of corticosteroids, and endoscopic and percutaneous procedures in the treatment of 86 cases of urogenital tuberculosis. Corticosteroids were coprescribed with tuberculostatic agents in 20 patients: 16 ureteral strictures were treated with 8 success and 8 failures, 8 contracted bladders were treated with 5 success and 3 failures. Three cases of retraction of the renal pelvis were treated by corticosteroids with 2 successes and one failure. Ureteral stricture was treated by retrograde ureteral stenting in 5 cases and by percutaneous antegrade ureteral stenting in one case with 4 successes and 2 failures. This study more clearly defines the indications for corticosteroids and endoscopic treatment with particular reference to new endoscopic surgery techniques. PMID:7825980

  7. The Effect of Garcin® in Preventing AntiTB-Induced Hepatitis in Newly Diagnosed Tuberculosis Patients

    PubMed Central

    Tabarsi, Payam; Fahimi, Fanak; Heidarzadeh, Nader; Haghgoo, Roodabeh; Kazempour, Mehdi; Masjedi, Mohammadreza; Velayati, Ali Akbar

    2014-01-01

    Adverse effects of antituberculosis agents such as hepatotoxicity may reduce treatment effectiveness, because they significantly contribute to nonadherence and eventually result in treatment failure, relapse or the emergence of drug resistance. Garlic is an ancient herbal substance, which its effectiveness on isoniazid and rifampicin-induced hepatic injury in animal models has been demonstrated (1). In the present study a randomized, double blind, placebo-controlled, parallel group clinical trial was designed to assess the effect(s) of garlic tablets (1000 mg daily) administered for two weeks orally. Fifty eight newly diagnosed, smear positive pulmonary tuberculosis patients, with age ranges between 18-65 years old, were randomly allocated into two groups. Each patient received either garlic or placebo tablets for the first two weeks of tuberculosis treatment. Of total 58 patients, 31 received garlic tablets while 27 received placebo. No significant difference was found between the two groups regarding age, sex, nationality, smoking, underlying diseases and opium usage. During 8 weeks of anti-TB (antituberculosis) treatment, 8 (13.0%) patients developed drug-induced hepatotoxicity (DIH). Of them, 6 (75%) occurred in the first two weeks of treatment. Fifty percent of the patients who developed DIH were in garlic group. Results indicated no significant difference between groups in developing DIH (p=1.000). We could not show a significant role in preventing DIH by 1000 mg daily garlic administration. PMID:24711843

  8. The Effect of Garcin® in Preventing AntiTB-Induced Hepatitis in Newly Diagnosed Tuberculosis Patients.

    PubMed

    Tabarsi, Payam; Fahimi, Fanak; Heidarzadeh, Nader; Haghgoo, Roodabeh; Kazempour, Mehdi; Masjedi, Mohammadreza; Velayati, Ali Akbar

    2014-01-01

    Adverse effects of antituberculosis agents such as hepatotoxicity may reduce treatment effectiveness, because they significantly contribute to nonadherence and eventually result in treatment failure, relapse or the emergence of drug resistance. Garlic is an ancient herbal substance, which its effectiveness on isoniazid and rifampicin-induced hepatic injury in animal models has been demonstrated (1). In the present study a randomized, double blind, placebo-controlled, parallel group clinical trial was designed to assess the effect(s) of garlic tablets (1000 mg daily) administered for two weeks orally. Fifty eight newly diagnosed, smear positive pulmonary tuberculosis patients, with age ranges between 18-65 years old, were randomly allocated into two groups. Each patient received either garlic or placebo tablets for the first two weeks of tuberculosis treatment. Of total 58 patients, 31 received garlic tablets while 27 received placebo. No significant difference was found between the two groups regarding age, sex, nationality, smoking, underlying diseases and opium usage. During 8 weeks of anti-TB (antituberculosis) treatment, 8 (13.0%) patients developed drug-induced hepatotoxicity (DIH). Of them, 6 (75%) occurred in the first two weeks of treatment. Fifty percent of the patients who developed DIH were in garlic group. Results indicated no significant difference between groups in developing DIH (p=1.000). We could not show a significant role in preventing DIH by 1000 mg daily garlic administration. PMID:24711843

  9. The medical and surgical treatment of drug-resistant tuberculosis

    PubMed Central

    Calligaro, Gregory L.; Moodley, Loven; Symons, Greg

    2014-01-01

    Multi drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB) are burgeoning global problems with high mortality which threaten to destabilise TB control programs in several parts of the world. Of alarming concern is the emergence, in large numbers, of patients with resistance beyond XDR-TB (totally drug-resistant TB; TDR-TB or extremely drug resistant TB; XXDR-TB). Given the burgeoning global phenomenon of MDR-TB, XDR-TB and TDR-TB, and increasing international migration and travel, healthcare workers, researchers, and policy makers in TB endemic and non-endemic countries should familiarise themselves with issues relevant to the management of these patients. Given the lack of novel TB drugs and limited access to existing drugs such as linezolid and bedaquiline in TB endemic countries, significant numbers of therapeutic failures are emerging from the ranks of those with XDR-TB. Given the lack of appropriate facilities in resource-limited settings, such patients are being discharged back into the community where there is likely ongoing disease spread. In the absence of effective drug regimens, in appropriate patients, surgery is a critical part of management. Here we review the diagnosis, medical and surgical management of MDR-TB and XDR-TB. PMID:24624282

  10. Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment

    PubMed Central

    2013-01-01

    Background New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA). Methods The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR. Results The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals. Conclusion UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB. PMID:24098949

  11. Reducing the price of treatment for multidrug-resistant tuberculosis through the Global Drug Facility

    PubMed Central

    Cordier-Lassalle, Thierry; Keravec, Joel

    2015-01-01

    Abstract Problem Many countries have limited experience of securing the best prices for drugs and have little negotiating power. This is particularly true for the complex, lengthy and expensive regimens used to treat multidrug-resistant tuberculosis. Approach The Stop TB Partnership’s Global Drug Facility is dedicated to improving worldwide access to antituberculosis medicines and diagnostic techniques that meet international quality standards. Local setting The Global Drug Facility is able to secure price reductions through competitive tendering among prequalified drug manufacturers and by consolidating orders to achieve large purchase volumes. Consolidating the market in this way increases the incentives for suppliers of quality-assured medicines. Relevant changes In 2013 the Global Drug Facility reduced the price of the second-line drugs it supplies for multidrug-resistant tuberculosis: the overall cost of the longest and most expensive treatment regimen for a patient decreased by 26% – from 7890 United States dollars (US$) in 2011 to US$ 5822 in 2013. Lessons learnt The price of treatment for multidrug-resistant tuberculosis supplied by the Global Drug Facility was reduced by consolidating orders to achieve large purchase volumes, by international, competitive bidding and by the existence of donor-funded medicine stockpiles. The rise in the number of suppliers of internationally quality-assured drugs was also important. The savings achieved from lower drug costs could be used to increase the number of patients on high-quality treatment. PMID:26229192

  12. Plasma Adenosine Deaminase Enzyme Reduces with Treatment of Pulmonary Tuberculosis in Nigerian Patients: Indication for Diagnosis and Treatment Monitoring.

    PubMed

    Ige, O; Edem, V F; Arinola, O G

    2016-01-01

    Tuberculosis(TB)-specific host biomarkers for diagnosis and monitoring of treatment response have been identified as priorities for TB research. Macrophage and T cell lymphocytes play vital roles in Mycobacterium tuberculosis immune response and their associated biomarkers could form good candidates for diagnosis and treatment monitoring. The enzyme adenosine deaminase (ADA) is produced mainly by monocytes and macrophages and increase in biological fluids in the course of infection with microorganisms infecting macrophages. This study comprised sixty-eight (68) participants; twenty-four (24) multi-drug-resistant TB(MDR-TB) patients, twenty-four (24) drug-sensitive TB patients(DS-TB) and twenty (20) non-TB apparently healthy individuals. Five (5) milliliters of blood was drawn before commencement of chemotherapy and 6 anti-TB therapy. In DSTB and MDR-TB patients before commencement of chemotherapy and 6 months of anti-TB treatment, the mean plasma levels of ADA were significantly increased compared with control. At 6 months of anti-TB chemotherapy of DSTB or MDR TB patients, ADA level was significantly decreased compared with before chemotherapy. Plasma ADA in DSTB patients before and 6 months of chemotherapy were not significantly different compared MDR TB patients. Plasma ADA level is a promising biomarker for the screening and treatment monitoring of pulmonary tuberculosis but not to differentiate MDR TB from DSTB patients. PMID:27574764

  13. Pattern of primary tuberculosis drug resistance and associated treatment outcomes in Transnistria, Moldova.

    PubMed

    Dolgusev, O; Obevzenco, N; Padalco, O; Pankrushev, S; Ramsay, A; Van den Bergh, R; Manzi, M; Denisiuk, O; Zachariah, R

    2014-10-21

    This cohort study assessed drug susceptibility testing (DST) patterns and associated treatment outcomes from Transnistria, Moldova, from 2009 to 2012. Of 1089 newly registered tuberculosis (TB) patients with available DST results, 556 (51%) had some form of drug resistance, while 369 (34%) had multidrug-resistant TB (MDR-TB). There were four cases of extensively drug-resistant TB. MDR-TB patients had poor treatment success (45%); human immunodeficiency virus positivity and a history of incarceration were associated with an unfavourable treatment outcome. This first study from Trans-nistria shows a high level of drug-resistant TB, which constitutes a major public health problem requiring urgent attention.

  14. Tuberculosis treatment outcomes among retreatment patients registered by private practitioners in Myanmar.

    PubMed

    Win, A N; Edginton, M E; Hinderaker, S G; Minn, N N; Linn, A K

    2012-09-21

    The objectives of this retrospective cohort study were to report treatment outcomes and identify factors associated with treatment failure among all retreatment tuberculosis (TB) patients registered in the public-private mix DOTS programme of Populations Services International-Myanmar over 6 years. Among 3643 retreatment patients, 2657 (73%) were successfully treated and 309 (8.5%) failed. This study shows that retreatment patients who have failed treatment for their first TB episode are almost twice as likely to fail a second time (13.5%). We have identified some key programmatic challenges associated with retreatment TB in the private sector, and steps are being taken to address this issue.

  15. Delay in diagnosis of tuberculosis in Rawalpindi, Pakistan

    PubMed Central

    2011-01-01

    Background Delay in diagnosis and treatment of tuberculosis (TB) may enhance the chances of morbidity and mortality and play a key role in continuous transmission of the bacilli. The objective of this study was to describe health care seeking behavior of suspected TB patients and initial diagnostic work up prior to consultation and diagnosis at National TB Center (NTC). Findings Interviews of 252 sputum smear positive patients were taken from NTC, Rawalpindi. The duration between on-set of symptoms and start of treatment was considered as the total delay and correlated with general characteristics of TB patients. The proportion of males and females were 49.6% and 50.4% with median age of 25 and 24 years respectively. A median delay of 56 days (8 weeks) was observed which was significantly associated with age, cough and fever. More than 50% of the current patients had a history of contact with previously diagnosed TB patients. The majority of patients (63%) visited health care providers within three weeks of appearance of symptoms but only thirty five percent were investigated for TB diagnosis. Conclusion Cough and fever are being ignored as likely symptoms of TB by patients as well as health care providers resulting in delay. Engaging private practitioners through public private mix (PPM) approach for expansion of TB diagnosis and increasing public awareness could be more beneficial to reduce delay. PMID:21615946

  16. Tuberculosis control in South Africa: successes, challenges and recommendations.

    PubMed

    Churchyard, G J; Mametja, L D; Mvusi, L; Ndjeka, N; Hesseling, A C; Reid, A; Babatunde, S; Pillay, Y

    2014-03-01

    Tuberculosis (TB) remains a global health threat, and South Africa (SA) has one of the world's worst TB epidemics driven by HIV. Among the 22 countries with the highest burden of TB, SA has the highest estimated incidence and prevalence of TB, the second highest number of diagnosed multidrug-resistant TB cases, and the largest number of HIV-associated TB cases. Although SA has made notable progress in reducing TB prevalence and deaths and improving treatment outcomes for new smear-positive TB cases, the burden of TB remains enormous. SA has the means to overcome this situation. In addition to better implementing the basics of TB diagnosis and treatment, scaling up the use of Xpert MTB/RIF as a replacement for sputum smear microscopy, strengthening case finding in and beyond healthcare facilities and a greater focus on TB prevention for people living with HIV, particularly earlier initiation of and scaling up antiretroviral therapy and scaling up continuous isoniazid preventive therapy, will have a substantial impact on TB control. New TB drugs, diagnostics and vaccines are required to further accelerate progress towards improved TB control in SA and beyond. PMID:24893501

  17. Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomised placebo controlled trials

    PubMed Central

    Wilkinson, David; Squire, S B; Garner, Paul

    1998-01-01

    Objective: To determine whether preventive treatment for tuberculosis in adults infected with HIV reduces the frequency of tuberculosis and overall mortality. Design: Systematic review and data synthesis of randomised placebo controlled trials. Main outcome measures: Active tuberculosis, mortality, and adverse drug reaction requiring cessation of the study regimen. Outcomes stratified by status of purified protein derivative skin test. Results: Four trials comprising 4055 adults from Haiti, Kenya, the United States, and Uganda were included. All compared isoniazid (6-12 months) with placebo, and one trial also compared multidrug treatment for 3 months with placebo. Mean follow up was 15-33 months. Overall, frequency of tuberculosis (relative risk 0.57, 95% confidence interval 0.41 to 0.79) was reduced in those receiving preventive treatment compared with placebo: mortality was not significantly reduced (0.93, 0.83 to 1.05). In subjects positive for purified protein derivative receiving preventive treatment, the risk of tuberculosis was reduced substantially (0.32, 0.19 to 0.51) and the risk of death was reduced moderately (0.73, 0.57 to 0.95) compared with those taking placebo. In adults negative for purified protein derivative receiving preventive treatment, the risk of tuberculosis (0.82, 0.50 to 1.36) and the risk of death (1.02, 0.89 to 1.17) were not reduced significantly. Adverse drug reactions were more frequent, but not significantly so, in patients receiving drug compared with placebo (1.45, 0.98 to 2.14). Conclusions: Preventive treatment given for 3-12 months protects against tuberculosis in adults infected with HIV, at least in the short to medium term. Protection is greatest in subjects positive for purified protein derivative, in whom death is also less frequent. Long term benefits remain to be shown. Key messages One third of the world’s population is infected with Mycobacterium tuberculosis People infected with HIV are at much increased risk of

  18. Community health workers improve contact tracing among immigrants with tuberculosis in Barcelona

    PubMed Central

    2012-01-01

    Background The important increase in immigration during recent years has changed the epidemiology and control strategies for tuberculosis (TB) in many places. This study evaluates the effectiveness of intervention with community health workers (CHW) to improve contact tracing among immigrants. Methods The study included all TB cases detected by the Barcelona TB Program from 2000 to 2005 and compared a period without CHW intervention (2000-2002) to a period with CHW intervention (2003-2005). The influence on contact tracing of sex, age, hospital of diagnosis, district of residence, birthplace, HIV, homeless and CHW intervention was analysed by logistic regression. Odds ratio (OR) and 95% confidence intervals (CI) were calculated. Results 960 foreign born TB cases were detected, 388 in the intervention period. Contact tracing was performed on 65,7% of 201 smear-positive cases during the pre-intervention period compared to 81.6% of 152 smear-positive TB cases during the intervention period (p < 0.001). Risk factors associated with incomplete contact tracing of smear-positive index cases included being diagnosed in two hospitals without contact tracing TB unit (OR = 3.5; CI:1.4-8.9) and (OR = 4.6; CI:1.6-13.5) respectively, birth place in India-Pakistan (OR = 4.4; CI:1.9-10.3) or North Africa (OR = 4.3; CI:1.8-10.5), having an unknown residence (OR = 5.4; CI:1.6-18.0), being HIV-infected (OR = 6.1; CI:2.5-14.8) or homeless (OR = 3.3; CI:1.3-8.2), and the absence of CHW intervention (OR = 2.4; CI:1.3-4.3). Conclusions The effectiveness of contact tracing for TB control in areas with high immigration can be improved by incorporating CHWs who act as translators, cultural mediators and facilitators who accompany cases and contacts through treatment and follow-up. PMID:22394990

  19. Impact of tuberculosis treatment length and adherence under different transmission intensities.

    PubMed

    Pinho, S T R; Rodrigues, P; Andrade, R F S; Serra, H; Lopes, J S; Gomes, M G M

    2015-09-01

    Tuberculosis (TB) is a leading cause of human mortality due to infectious disease. Treatment default is a relevant factor which reduces therapeutic success and increases the risk of resistant TB. In this work we analyze the relation between treatment default and treatment length along with its consequence on the disease spreading. We use a stylized model structure to explore, systematically, the effects of varying treatment duration and compliance. We find that shortening treatment alone may not reduce TB prevalence, especially in regions where transmission intensity is high, indicating the necessity of complementing this action with increased compliance. A family of default functions relating the proportion of defaulters to the treatment length is considered and adjusted to a particular dataset. We find that the epidemiological benefits of shorter treatment regimens are tightly associated with increases in treatment compliance and depend on the epidemiological background.

  20. Analyzing seasonality of tuberculosis across Indian states and union territories.

    PubMed

    Narula, Pankaj; Sihota, Praveer; Azad, Sarita; Lio, Pietro

    2015-12-01

    A significant seasonal variation in tuberculosis (TB) is observed in north India during 2006-2011, particularly in states like Himachal Pradesh, Haryana and Rajasthan. To quantify the seasonal variation, we measure average amplitude (peak to trough distance) across seasons in smear positive cases of TB and observe that it is maximum for Himachal Pradesh (40.01%) and minimum for Maharashtra (3.87%). In north India, smear positive cases peak in second quarter (April-June) and reach a trough in fourth quarter (October-December), however low seasonal variation is observed in southern region of the country. The significant correlations as 0.64 (p-value<0.001), 0.54 (p-value<0.01) and 0.42 (p-value<0.05) are observed between minimum temperature and seasonality of TB at lag-1 in north, central and northeast India respectively. However, in south India, this correlation is not significant.

  1. Postpartum Tuberculosis: A Diagnostic and Therapeutic Challenge

    PubMed Central

    Gudeta, Alemeshet; Zerihun, Aklilu; Lewis, Odene; Ahmed, Sohail; Gajjala, Jhansi; Thomas, Alicia

    2016-01-01

    Tuberculosis (TB) infection in pregnant women and newborn babies is always challenging. Appropriate treatment is pivotal to curtail morbidity and mortality. TB diagnosis or exposure to active TB can be emotionally distressing to the mother. Circumstances can become more challenging for the physician if the mother's TB status is unclear. Effective management of TB during pregnancy and the postpartum period requires a multidisciplinary approach including pulmonologist, obstetrician, neonatologist, infectious disease specialist, and TB public health department. Current guidelines recommend primary Isoniazid prophylaxis in TB exposed pregnant women who are immune-suppressed and have chronic medical conditions or obstetric risk factors and close and sustained contact with a patient with infectious TB. Treatment during pregnancy is the same as for the general adult population. Infants born to mothers with active TB at delivery should undergo a complete diagnostic evaluation. Primary Isoniazid prophylaxis for at least twelve weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. This case highlights important aspects for management of TB during the postpartum period which has a higher morbidity. We present a case of a young mother migrating from a developing nation to the USA, who was found to have a positive quantiFERON test associated with multiple cavitary lung lesions and gave birth to a healthy baby. PMID:27610260

  2. Postpartum Tuberculosis: A Diagnostic and Therapeutic Challenge.

    PubMed

    Kodadhala, Vijay; Gudeta, Alemeshet; Zerihun, Aklilu; Lewis, Odene; Ahmed, Sohail; Gajjala, Jhansi; Thomas, Alicia

    2016-01-01

    Tuberculosis (TB) infection in pregnant women and newborn babies is always challenging. Appropriate treatment is pivotal to curtail morbidity and mortality. TB diagnosis or exposure to active TB can be emotionally distressing to the mother. Circumstances can become more challenging for the physician if the mother's TB status is unclear. Effective management of TB during pregnancy and the postpartum period requires a multidisciplinary approach including pulmonologist, obstetrician, neonatologist, infectious disease specialist, and TB public health department. Current guidelines recommend primary Isoniazid prophylaxis in TB exposed pregnant women who are immune-suppressed and have chronic medical conditions or obstetric risk factors and close and sustained contact with a patient with infectious TB. Treatment during pregnancy is the same as for the general adult population. Infants born to mothers with active TB at delivery should undergo a complete diagnostic evaluation. Primary Isoniazid prophylaxis for at least twelve weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. This case highlights important aspects for management of TB during the postpartum period which has a higher morbidity. We present a case of a young mother migrating from a developing nation to the USA, who was found to have a positive quantiFERON test associated with multiple cavitary lung lesions and gave birth to a healthy baby. PMID:27610260

  3. Postpartum Tuberculosis: A Diagnostic and Therapeutic Challenge

    PubMed Central

    Gudeta, Alemeshet; Zerihun, Aklilu; Lewis, Odene; Ahmed, Sohail; Gajjala, Jhansi; Thomas, Alicia

    2016-01-01

    Tuberculosis (TB) infection in pregnant women and newborn babies is always challenging. Appropriate treatment is pivotal to curtail morbidity and mortality. TB diagnosis or exposure to active TB can be emotionally distressing to the mother. Circumstances can become more challenging for the physician if the mother's TB status is unclear. Effective management of TB during pregnancy and the postpartum period requires a multidisciplinary approach including pulmonologist, obstetrician, neonatologist, infectious disease specialist, and TB public health department. Current guidelines recommend primary Isoniazid prophylaxis in TB exposed pregnant women who are immune-suppressed and have chronic medical conditions or obstetric risk factors and close and sustained contact with a patient with infectious TB. Treatment during pregnancy is the same as for the general adult population. Infants born to mothers with active TB at delivery should undergo a complete diagnostic evaluation. Primary Isoniazid prophylaxis for at least twelve weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. This case highlights important aspects for management of TB during the postpartum period which has a higher morbidity. We present a case of a young mother migrating from a developing nation to the USA, who was found to have a positive quantiFERON test associated with multiple cavitary lung lesions and gave birth to a healthy baby.

  4. Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal Fixation via Posterior Approach Only.

    PubMed

    Tang, Ming-xing; Zhang, Hong-qi; Wang, Yu-xiang; Guo, Chao-feng; Liu, Jin-yang

    2016-02-01

    Surgical treatment for spinal tuberculosis includes focal tuberculosis debridement, segmental stability reconstruction, neural decompression and kyphotic deformity correction. For the lesions mainly involved anterior and middle column of the spine, anterior operation of debridement and fusion with internal fixation has been becoming the most frequently used surgical technique for the spinal tuberculosis. However, high risk of structural damage might relate with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel, and the deformity correction is also limited. Due to the organs are in the front of spine, there are less complications in posterior approach. Spinal pedicle screw passes through the spinal three-column structure, which provides more powerful orthopedic forces compared with the vertebral body screw, and the kyphotic deformity correction effect is better in posterior approach. In this paper, we report a 68-year-old male patient with thoracic tuberculosis who underwent surgical treatment by debridement, interbody fusion and internal fixation via posterior approach only. The patient was placed in prone position under general anesthesia. Posterior midline incision was performed, and the posterior spinal construction was exposed. Then place pedicle screw, and fix one side rod temporarily. Make the side of more bone destruction and larger abscess as lesion debridement side. Resect the unilateral facet joint, and retain contralateral structure integrity. Protect the spinal cord, nerve root. Clear sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space. Specially designed titanium mesh cages or bone blocks were implanted into interbody. Fix both side rods and compress both sides to make the mesh cages and bone blocks tight. Reconstruct posterior column structure with allogeneic bone and autologous bone. Using this technique, the procedures of debridement, spinal cord decompression, deformity correction, bone grafting

  5. Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal Fixation via Posterior Approach Only.

    PubMed

    Tang, Ming-xing; Zhang, Hong-qi; Wang, Yu-xiang; Guo, Chao-feng; Liu, Jin-yang

    2016-02-01

    Surgical treatment for spinal tuberculosis includes focal tuberculosis debridement, segmental stability reconstruction, neural decompression and kyphotic deformity correction. For the lesions mainly involved anterior and middle column of the spine, anterior operation of debridement and fusion with internal fixation has been becoming the most frequently used surgical technique for the spinal tuberculosis. However, high risk of structural damage might relate with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel, and the deformity correction is also limited. Due to the organs are in the front of spine, there are less complications in posterior approach. Spinal pedicle screw passes through the spinal three-column structure, which provides more powerful orthopedic forces compared with the vertebral body screw, and the kyphotic deformity correction effect is better in posterior approach. In this paper, we report a 68-year-old male patient with thoracic tuberculosis who underwent surgical treatment by debridement, interbody fusion and internal fixation via posterior approach only. The patient was placed in prone position under general anesthesia. Posterior midline incision was performed, and the posterior spinal construction was exposed. Then place pedicle screw, and fix one side rod temporarily. Make the side of more bone destruction and larger abscess as lesion debridement side. Resect the unilateral facet joint, and retain contralateral structure integrity. Protect the spinal cord, nerve root. Clear sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space. Specially designed titanium mesh cages or bone blocks were implanted into interbody. Fix both side rods and compress both sides to make the mesh cages and bone blocks tight. Reconstruct posterior column structure with allogeneic bone and autologous bone. Using this technique, the procedures of debridement, spinal cord decompression, deformity correction, bone grafting

  6. Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal Fixation via Posterior Approach Only

    PubMed Central

    Tang, Ming‐xing; Wang, Yu‐xiang; Guo, Chao‐feng; Liu, Jin‐yang

    2016-01-01

    Surgical treatment for spinal tuberculosis includes focal tuberculosis debridement, segmental stability reconstruction, neural decompression and kyphotic deformity correction. For the lesions mainly involved anterior and middle column of the spine, anterior operation of debridement and fusion with internal fixation has been becoming the most frequently used surgical technique for the spinal tuberculosis. However, high risk of structural damage might relate with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel, and the deformity correction is also limited. Due to the organs are in the front of spine, there are less complications in posterior approach. Spinal pedicle screw passes through the spinal three‐column structure, which provides more powerful orthopedic forces compared with the vertebral body screw, and the kyphotic deformity correction effect is better in posterior approach. In this paper, we report a 68‐year‐old male patient with thoracic tuberculosis who underwent surgical treatment by debridement, interbody fusion and internal fixation via posterior approach only. The patient was placed in prone position under general anesthesia. Posterior midline incision was performed, and the posterior spinal construction was exposed. Then place pedicle screw, and fix one side rod temporarily. Make the side of more bone destruction and larger abscess as lesion debridement side. Resect the unilateral facet joint, and retain contralateral structure integrity. Protect the spinal cord, nerve root. Clear sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space. Specially designed titanium mesh cages or bone blocks were implanted into interbody. Fix both side rods and compress both sides to make the mesh cages and bone blocks tight. Reconstruct posterior column structure with allogeneic bone and autologous bone. Using this technique, the procedures of debridement, spinal cord decompression, deformity correction, bone

  7. [On the differences in attitude and awareness of clinical doctors, health administrators and other health workers to tuberculosis treatment in Japan and the US].

    PubMed

    Masuyama, H; Aoki, M

    2000-06-01

    Peculiarity of TB treatment in Japan is a higher rate and duration of hospitalization than in other developed countries. Improvement of the TB control policy in Japan necessitates reexamination of the issue of treatment policy, which requires consideration of recognition and understanding of the concept of TB infection, human rights and the protection of patients as well as the society. Therefore, this study aims at clarifying and analyzing the differences in TB treatment policies in Japan and the US. For the US, a questionnaire was sent to TB Directors of states and large cities in order to analyze TB control policies. Moreover, the author attended the NTCA meeting held in Chicago to interview 16 TB Directors. In Japan, the author sent the same questionnaire translated into Japanese to medical doctors in 54 National TB sanatoria. The hospitalization rates of new smear-positive TB patients were 100% (median) in Japan and 59% in the US. The periods of hospitalization of these patients were 150 days (median) in Japan and 10 days in the US. The total expenses of TB diagnosis and treatment per capita were approximately US $25,000 and 20,000, respectively in Japan and the US. If the DOT strategy were applied to the new smear-positive TB cases in Japan, those total expenses would be reduced to half. On the measures against the TB patients who pose a threat to the public, the US has the series of TB control strategies which contain the reporting system, home isolation, incarceration and penalties for violation, while Japan has only the strategy of hospitalization. The TB policies of Japan in future would need to focus more selectively and carry out thoroughly as seen in the US. The recommended TB policies for Japan obtained from this study are to set TB policies adapted to regional characteristics and to review the strategy against patients posing a threat to the public.

  8. Experience of active tuberculosis case finding in nearly 5 million households in India.

    PubMed

    Prasad, B M; Satyanarayana, S; Chadha, S S; Das, A; Thapa, B; Mohanty, S; Pandurangan, S; Babu, E R; Tonsing, J; Sachdeva, K S

    2016-03-21

    In India, to increase tuberculosis (TB) case detection under the National Tuberculosis Programme, active case finding (ACF) was implemented by the Global Fund-supported Project Axshya, among high-risk groups in 300 districts. Between April 2013 and December 2014, 4.9 million households covering ~20 million people were visited. Of 350 047 presumptive pulmonary TB cases (cough of ⩾2 weeks) identified, 187 586 (54%) underwent sputum smear examination and 14 447 (8%) were found to be smear-positive. ACF resulted in the detection of a large number of persons with presumptive pulmonary TB and smear-positive TB. Ensuring sputum examination of all those with presumptive TB was a major challenge.

  9. Impact of Latent Infection Treatment in Indigenous Populations

    PubMed Central

    Yuhara, Lucia Suemi; Sacchi, Flávia Patussi Correia; Croda, Julio

    2013-01-01

    The aims of the present study were to identify risk factors associated with latent tuberculosis (TB), examine the development of active disease among contacts, and assess the effectiveness of treating latent infection in indigenous Brazilians from January 2006 to December 2011. This was a retrospective study consisting of 1,371 tuberculosis contacts, 392 of whom underwent treatment for latent infection. Morbidity-from-TB data were obtained from the Information System for Disease Notification (SINAN) database, and the contacts’ data were collected from the clinical records using forms employed by Special Department of Indigenous Health (SESAI) multidisciplinary teams, according to SESAI’s instructions. The variables that were associated with latent infection among the contacts were age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02–1.04) and close contact with a smear-positive index case (OR: 2.26, 95% CI: 1.59–3.22). The variables associated with the development of active TB among the contacts were a tuberculin skin test (TST) ≥10 mm (relative risk [RR]: 1.12, 95% CI: 1.07–1.17), age (RR: 1.01, 95% CI: 1.00–1.03), and treatment of latent infection (RR: 0.03, 95% CI: 0.01–0.27). The estimated number of latent infection treatments needed to prevent one case of active TB among the contacts was 51 treatments (95% CI: 33–182). In contacts with TST ≥10 mm, 10 (95% CI: 6–19) latent infection treatments were necessary to prevent one case of active TB. Age and close contact with a smear-positive index case were associated with latent TB. Screening with TST is a high priority among individuals contacting smear-positive index cases. Age and TST are associated with the development of active TB among contacts, and treatment of latent infection is an effective measure to control TB in indigenous communities. PMID:23936264

  10. Recommendations Concerning the First-Line Treatment of Children with Tuberculosis.

    PubMed

    Principi, Nicola; Galli, Luisa; Lancella, Laura; Tadolini, Marina; Migliori, Giovanni Battista; Villani, Alberto; Esposito, Susanna

    2016-02-01

    This document describes the recommendations of a group of scientific societies concerning the first-line therapeutic approach to paediatric tuberculosis (TB). The treatment of pulmonary TB should be based on the existence of parenchymal involvement and the risk of antibiotic resistance. The treatment of extra-pulmonary TB is based on the regimens used for severe pulmonary TB. The administration of corticosteroids is recommended only in cases of miliary TB, tuberculous meningitis and tuberculous pericarditis. Vitamin B6 may be indicated in the case of isoniazid-treated TB in breastfeeding infants, severely malnourished subjects, or patients with other diseases at high risk of vitamin deficiency. Once having started treatment, children with TB should be carefully followed up in order to evaluate compliance, the response to treatment, the need for treatment changes, and the presence of drug-related adverse events. Primary care paediatricians can support reference centres in providing family healthcare education and encouraging treatment compliance.

  11. Tuberculosis in hospitalized patients: clinical characteristics of patients receiving treatment within the first 24 h after admission*

    PubMed Central

    Silva, Denise Rossato; da Silva, Larissa Pozzebon; Dalcin, Paulo de Tarso Roth

    2014-01-01

    Objective: To evaluate clinical characteristics and outcomes in patients hospitalized for tuberculosis, comparing those in whom tuberculosis treatment was started within the first 24 h after admission with those who did not. Methods: This was a retrospective cohort study involving new tuberculosis cases in patients aged ≥ 18 years who were hospitalized after seeking treatment in the emergency room. Results: We included 305 hospitalized patients, of whom 67 (22.0%) received tuberculosis treatment within the first 24 h after admission ( ≤24h group) and 238 (88.0%) did not (>24h group). Initiation of tuberculosis treatment within the first 24 h after admission was associated with being female (OR = 1.99; 95% CI: 1.06-3.74; p = 0.032) and with an AFB-positive spontaneous sputum smear (OR = 4.19; 95% CI: 1.94-9.00; p < 0.001). In the ≤24h and >24h groups, respectively, the ICU admission rate was 22.4% and 15.5% (p = 0.258); mechanical ventilation was used in 22.4% and 13.9% (p = 0.133); in-hospital mortality was 22.4% and 14.7% (p = 0.189); and a cure was achieved in 44.8% and 52.5% (p = 0.326). Conclusions: Although tuberculosis treatment was initiated promptly in a considerable proportion of the inpatients evaluated, the rates of in-hospital mortality, ICU admission, and mechanical ventilation use remained high. Strategies for the control of tuberculosis in primary care should consider that patients who seek medical attention at hospitals arrive too late and with advanced disease. It is therefore necessary to implement active surveillance measures in the community for earlier diagnosis and treatment. PMID:25029651

  12. Treatment Adherence of Tuberculosis Patients Attending Two Reference Units in Equatorial Guinea

    PubMed Central

    Eyene, Juan; Momo, Juan Carlos; Biyé, Lucia; Esono, Teodoro; Ondó Mba Ayecab, Marcial; Benito, Agustín; Aparicio, Pilar

    2016-01-01

    Equatorial Guinea has one of the highest burden of tuberculosis (TB) in Africa. Incomplete adherence to TB treatment has been identified as one of the most serious remaining problem in tuberculosis control. The following study is aimed at determining the adherence to anti-tuberculosis treatment in Equatorial Guinea and its determinants, as well as at assessing the knowledge of the people about the disease. In this cross-sectional study, participants were recruited by non-probabilistic consecutive sampling amongst patients who attended the reference units for TB in Bata and Malabo between March and July 2015. Socio-demographic and clinical data were collected. Adherence to treatment and knowledge about TB were assessed by Morisky-Green-Levine and Batalla tests and a questionnaire on adherence related factors specifically prepared for this research. Descriptive statistics were computed to summarize the data and bivariate analyses by adherence profile were performed with χ2 test for categorical data. A total of 98 patients with TB were interviewed. 63.27% of interviewees had good knowledge about TB (Batalla test) while 78.57% of respondents were adherent according to the Morisky-Green-Levine test. A low educational level, lack of family support and lack of medical advice about the disease were significantly associated to lower adherence level. Patients with re-infection (due to relapse or treatment failure) and those who have suffered from drug shortages were also less adherents. The National Programme for TB Control should consider improving the early diagnosis and follow-up of TB cases, as well as the implementation of all components of DOTS (Directly observed Treatment, short-course) strategy all over the country. PMID:27622461

  13. Treatment Adherence of Tuberculosis Patients Attending Two Reference Units in Equatorial Guinea.

    PubMed

    Fagundez, Gabriela; Perez-Freixo, Hugo; Eyene, Juan; Momo, Juan Carlos; Biyé, Lucia; Esono, Teodoro; Ondó Mba Ayecab, Marcial; Benito, Agustín; Aparicio, Pilar; Herrador, Zaida

    2016-01-01

    Equatorial Guinea has one of the highest burden of tuberculosis (TB) in Africa. Incomplete adherence to TB treatment has been identified as one of the most serious remaining problem in tuberculosis control. The following study is aimed at determining the adherence to anti-tuberculosis treatment in Equatorial Guinea and its determinants, as well as at assessing the knowledge of the people about the disease. In this cross-sectional study, participants were recruited by non-probabilistic consecutive sampling amongst patients who attended the reference units for TB in Bata and Malabo between March and July 2015. Socio-demographic and clinical data were collected. Adherence to treatment and knowledge about TB were assessed by Morisky-Green-Levine and Batalla tests and a questionnaire on adherence related factors specifically prepared for this research. Descriptive statistics were computed to summarize the data and bivariate analyses by adherence profile were performed with χ2 test for categorical data. A total of 98 patients with TB were interviewed. 63.27% of interviewees had good knowledge about TB (Batalla test) while 78.57% of respondents were adherent according to the Morisky-Green-Levine test. A low educational level, lack of family support and lack of medical advice about the disease were significantly associated to lower adherence level. Patients with re-infection (due to relapse or treatment failure) and those who have suffered from drug shortages were also less adherents. The National Programme for TB Control should consider improving the early diagnosis and follow-up of TB cases, as well as the implementation of all components of DOTS (Directly observed Treatment, short-course) strategy all over the country. PMID:27622461

  14. Treatment Adherence of Tuberculosis Patients Attending Two Reference Units in Equatorial Guinea.

    PubMed

    Fagundez, Gabriela; Perez-Freixo, Hugo; Eyene, Juan; Momo, Juan Carlos; Biyé, Lucia; Esono, Teodoro; Ondó Mba Ayecab, Marcial; Benito, Agustín; Aparicio, Pilar; Herrador, Zaida

    2016-01-01

    Equatorial Guinea has one of the highest burden of tuberculosis (TB) in Africa. Incomplete adherence to TB treatment has been identified as one of the most serious remaining problem in tuberculosis control. The following study is aimed at determining the adherence to anti-tuberculosis treatment in Equatorial Guinea and its determinants, as well as at assessing the knowledge of the people about the disease. In this cross-sectional study, participants were recruited by non-probabilistic consecutive sampling amongst patients who attended the reference units for TB in Bata and Malabo between March and July 2015. Socio-demographic and clinical data were collected. Adherence to treatment and knowledge about TB were assessed by Morisky-Green-Levine and Batalla tests and a questionnaire on adherence related factors specifically prepared for this research. Descriptive statistics were computed to summarize the data and bivariate analyses by adherence profile were performed with χ2 test for categorical data. A total of 98 patients with TB were interviewed. 63.27% of interviewees had good knowledge about TB (Batalla test) while 78.57% of respondents were adherent according to the Morisky-Green-Levine test. A low educational level, lack of family support and lack of medical advice about the disease were significantly associated to lower adherence level. Patients with re-infection (due to relapse or treatment failure) and those who have suffered from drug shortages were also less adherents. The National Programme for TB Control should consider improving the early diagnosis and follow-up of TB cases, as well as the implementation of all components of DOTS (Directly observed Treatment, short-course) strategy all over the country.

  15. Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis.

    PubMed

    Martineau, Adrian R

    2012-02-01

    Tuberculosis (TB) is a major cause of mortality, responsible for 1·68 million deaths worldwide in 2009. The global prevalence of latent Mycobacterium tuberculosis infection is estimated to be 32%, and this carries a 5-20% lifetime risk of reactivation disease. The emergence of drug-resistant organisms necessitates the development of new agents to enhance the response to antimicrobial therapy for active TB. Vitamin D was used to treat TB in the pre-antibiotic era, and its active metabolite, 1,25-dihydoxyvitamin D, has long been known to enhance the immune response to mycobacteria in vitro. Vitamin D deficiency is common in patients with active TB, and several clinical trials have evaluated the role of adjunctive vitamin D supplementation in its treatment. Results of these studies are conflicting, reflecting variation between studies in baseline vitamin D status of participants, dosing regimens and outcome measures. Vitamin D deficiency is also recognised to be highly prevalent among people with latent M. tuberculosis infection in both high- and low-burden settings, and there is a wealth of observational epidemiological evidence linking vitamin D deficiency with increased risk of reactivation disease. Randomised controlled trials of vitamin D supplementation for the prevention of active TB have yet to be performed, however. The conduct of such trials is a research priority, given the safety and low cost of vitamin D supplementation, and the potentially huge public health consequences of positive results.

  16. Cost and cost-effectiveness of multidrug-resistant tuberculosis treatment in Estonia and Russia.

    PubMed

    Floyd, Katherine; Hutubessy, Raymond; Kliiman, Kai; Centis, Rosella; Khurieva, Nina; Jakobowiak, Wieslaw; Danilovits, Manfred; Peremitin, Genadi; Keshavjee, Salmaan; Migliori, Giovanni Battista

    2012-07-01

    Evidence on the cost and cost-effectiveness of treatment of multidrug-resistant tuberculosis (MDR-TB) is limited, and no published data are available from former Soviet Union countries, where rates of MDR-TB are highest globally. We evaluated the cost and cost-effectiveness of MDR-TB treatment in Estonia and Russia (Tomsk Oblast), comparing cohorts enrolled on treatment according to World Health Organization (WHO) guidelines in 2001 and 2002 with cohorts treated in previous years. Costs were assessed from a health system perspective in 2003 US$; effects were measured as cures, deaths averted and disability-adjusted life-years (DALYs) averted. Cure rates when WHO guidelines were followed were 61% (90 out of 149) in Estonia and 76% (76 out of 100) in Tomsk Oblast, with a cost per patient treated of US$8,974 and US$10,088, respectively. Before WHO guidelines were followed, cure rates were 52% in Estonia and 15% in Tomsk Oblast; the cost per patient treated was US$4,729 and US$2,282, respectively. Drugs and hospitalisation accounted for 69-90% of total costs. The cost per DALY averted by treatment following WHO guidelines was US$579 (range US$297-US$902) in Estonia and US$429 (range US$302-US$546) in Tomsk Oblast. Treatment of patients with MDR-TB can be cost-effective, but requires substantial additional investment in tuberculosis control in priority countries. PMID:22362862

  17. Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

    PubMed Central

    Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria

    2016-01-01

    Objectives To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.

  18. Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

    PubMed Central

    Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria

    2016-01-01

    Objectives To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline. PMID:27708985

  19. Factors influencing non-adherence to tuberculosis treatment in Jepara, central Java, Indonesia.

    PubMed

    Rondags, Angelique; Himawan, Ari Budi; Metsemakers, Job Fm; Kristina, Tri Nur

    2014-07-01

    One of the most serious problems for tuberculosis (TB) control is non-adherence to TB treatment. We studied the factors influencing non-adherence to TB treatment in Indonesia to inform TB treatment adherence strategies. We con- ducted semi-structured interviews with non-adherent patients and key informants in Jepara, Central Java, Indonesia. Three major themes were found in reasons for non-adherence to TB treatment: 1) knowledge about TB, 2) knowledge about TB treatment and 3) choosing and changing a health care treatment facility. Respondents had an inadequate knowledge about TB and its treatment. Feeling healthy and having financial problems were the most common reasons for TB treatment non-adherence. Respondents sought treatment from many different health care providers, and often changed the treatment facility location. TB treatment adherence might improve by providing better education about the disease and its treatment to those undergoing treatment. Providing information about where to receive treatment and that treatment is free could also improve compliance.

  20. Outcomes and Treatment of Lumbosacral Spinal Tuberculosis: A Retrospective Study of 53 Patients

    PubMed Central

    He, Maolin; Wang, Kun; Fowdur, Mitra; Wu, Yang

    2015-01-01

    Study Strategy A retrospective clinic study. Purpose To evaluate the efficacy of conservative and surgical treatment for lumbosacral tuberculosis. Methods This study retrospectively reviewed 53 patients with lumbosacral tuberculosis who were treated in our institution between January 2005 and January 2011. There were 29 males and 24 females with average ages of 37.53 ± 17.28 years (range 6–72 years). 11 patients were given only anti-TB drugs; the remainder underwent anterior debridement, interbody fusion with and without instrumentation, or one-stage anterior debridement combined with posterior instrumentation. Outcome data for these patients included neurologic status, lumbosacral angle, erythrocyte sedimentation rate value(ESR) and C-reactive protein value(CRP) were assessed before and after treatment. Results The mean lumbosacral angles were 23.00°± 2.90°in the conservatively treated patients and 22.36°± 3.92o in the surgically treated patients. At the final follow-up, this had improved to 24.10o ± 2.96°in the conservatively treated patients and 28.13° ± 1.93°in the surgically treated patients (all P < 0.05). There were statistically significant differences before and after treatment in terms of ESR and CRP (all P < 0.05). All patients achieved bone fusion. The mean follow-up period was 32.34 ± 8.13 months (range 18 to 55 months). The neurological deficit did not worsen in any of the patients. Conclusions It has been proven that conservative and surgical treatments are safe and effective and produce good clinical outcomes for patients with lumbosacral tuberculosis. The advantages of operation include thoroughness of debridement, decompression of the spinal cord, and adequate spinal stabilization. PMID:26121685

  1. Ambulatory tuberculosis treatment in post-Semashko health care systems needs supportive financing mechanisms.

    PubMed

    Kohler, S; Asadov, D A; Bründer, A; Healy, S; Khamraev, A K; Sergeeva, N; Tinnemann, P

    2014-12-01

    The tuberculosis (TB) control strategy in the Republic of Karakalpakstan, Uzbekistan, is being changed to decentralised out-patient care for most TB patients by the Government of Uzbekistan, in collaboration with the international medical humanitarian organisation Médecins Sans Frontières. Ambulatory treatment of both drug-susceptible and drug-resistant TB from the first day of treatment has been recommended since 2011. Out-patient treatment of TB from the beginning of treatment was previously prohibited. However, the current Uzbek health financing system, which evolved from the Soviet Semashko model, offers incentives that work against the adoption of ambulatory TB treatment. Based on the 'Comprehensive TB Care for All' programme implemented in Karakalpakstan, we describe how existing policies for the allocation of health funds complicate the scale-up of ambulatory-based management of TB. PMID:25517802

  2. Disseminated tuberculosis infection and paradoxical reaction during antimycobacterial treatment related to TNF-alpha blocker agent Infliximab.

    PubMed

    Unlu, Mehmet; Cimen, Pınar; Ayranci, Aysu; Akarca, Tulay; Karaman, Onur; Dereli, Mustafa Sevket

    2014-01-01

    Tumor necrosis factor (TNF)-alpha inhibitors play an important role in the treatment of immun-mediated diseases such as Crohn's disease. But they also have been related to increased risk for disseminated Mycobacterium tuberculosis infections and paradoxical response to antimycobacterial treatment. Here we report a disseminated tuberculosis case and a paradoxical response to treatment after receiving TNF-inhibitor agent Infliximab for Crohn's disease. The patient had a severe clinical condition before the antimycobacterial treatment and although proper treatment was initiated his radiological findings were worsened one month after initiation of the treatment. All control microbologic tests for secondary infections were negative and this situation was accepted as a paradoxical response to antimycobacterial treatment and treatment was continued with the same regimen. At the end of the second month of the treatment, most of the symptoms disappeared and chest radiograph findings were better than the previous one. In conclusion, TNF-alpha inhibitor therapy increases risk of mycobacterial infections and patients should be examined carefully about tuberculosis before starting this therapy. Also, it is important for physicians to recognize and know how to manage paradoxical response related to TNF-alpha inhibitors during anti-tuberculosis treatment. PMID:26029559

  3. Disseminated tuberculosis infection and paradoxical reaction during antimycobacterial treatment related to TNF-alpha blocker agent Infliximab

    PubMed Central

    Unlu, Mehmet; Cimen, Pınar; Ayranci, Aysu; Akarca, Tulay; Karaman, Onur; Dereli, Mustafa Sevket

    2014-01-01

    Tumor necrosis factor (TNF)-alpha inhibitors play an important role in the treatment of immun-mediated diseases such as Crohn's disease. But they also have been related to increased risk for disseminated Mycobacterium tuberculosis infections and paradoxical response to antimycobacterial treatment. Here we report a disseminated tuberculosis case and a paradoxical response to treatment after receiving TNF-inhibitor agent Infliximab for Crohn's disease. The patient had a severe clinical condition before the antimycobacterial treatment and although proper treatment was initiated his radiological findings were worsened one month after initiation of the treatment. All control microbologic tests for secondary infections were negative and this situation was accepted as a paradoxical response to antimycobacterial treatment and treatment was continued with the same regimen. At the end of the second month of the treatment, most of the symptoms disappeared and chest radiograph findings were better than the previous one. In conclusion, TNF-alpha inhibitor therapy increases risk of mycobacterial infections and patients should be examined carefully about tuberculosis before starting this therapy. Also, it is important for physicians to recognize and know how to manage paradoxical response related to TNF-alpha inhibitors during anti-tuberculosis treatment. PMID:26029559

  4. Evaluating the potential impact of enhancing HIV treatment and tuberculosis control programmes on the burden of tuberculosis

    PubMed Central

    Chindelevitch, Leonid; Menzies, Nicolas A.; Pretorius, Carel; Stover, John; Salomon, Joshua A.; Cohen, Ted

    2015-01-01

    HIV has fuelled increasing tuberculosis (TB) incidence in sub-Saharan Africa. Better control of TB in this region may be achieved directly through TB programme improvements and indirectly through expanded use of antiretroviral therapy (ART) among those with HIV. We used a mathematical model of TB and HIV in South Africa to examine the potential epidemiological impact in scenarios involving improvements in three dimensions of TB programmes: coverage, diagnosis and treatment effectiveness, as well as expanded ART use through broadened eligibility. We projected the effect of alternative scenarios on TB prevalence, incidence and TB-related mortality over 20 years. Of the three dimensions of TB programme improvement, expanding coverage would produce the greatest reduction in TB burden. Compared with current performance, combined TB programme improvements were projected to decrease TB incidence by 30% over 5 years and 46% over 20 years, and decrease TB-related mortality by 45% over 5 years and 69% over 20 years. Expanded ART eligibility was projected to decrease TB incidence by 22% over 5 years and 45% over 20 years, and TB-related mortality by 22% over 5 years and 50% over 20 years. We found that over a 20-year horizon, TB-specific and HIV-specific programme changes contribute equally to incidence reductions, whereas the TB-specific changes produce a majority of the mortality benefits. An aggressive expansion of ART alongside traditional TB-specific control measures has the potential to greatly reduce TB burden, with the different elements of a combined approach having a synergistic effect in reducing long-term TB incidence and mortality. PMID:25878131

  5. Evaluating the potential impact of enhancing HIV treatment and tuberculosis control programmes on the burden of tuberculosis.

    PubMed

    Chindelevitch, Leonid; Menzies, Nicolas A; Pretorius, Carel; Stover, John; Salomon, Joshua A; Cohen, Ted

    2015-05-01

    HIV has fuelled increasing tuberculosis (TB) incidence in sub-Saharan Africa. Better control of TB in this region may be achieved directly through TB programme improvements and indirectly through expanded use of antiretroviral therapy (ART) among those with HIV. We used a mathematical model of TB and HIV in South Africa to examine the potential epidemiological impact in scenarios involving improvements in three dimensions of TB programmes: coverage, diagnosis and treatment effectiveness, as well as expanded ART use through broadened eligibility. We projected the effect of alternative scenarios on TB prevalence, incidence and TB-related mortality over 20 years. Of the three dimensions of TB programme improvement, expanding coverage would produce the greatest reduction in TB burden. Compared with current performance, combined TB programme improvements were projected to decrease TB incidence by 30% over 5 years and 46% over 20 years, and decrease TB-related mortality by 45% over 5 years and 69% over 20 years. Expanded ART eligibility was projected to decrease TB incidence by 22% over 5 years and 45% over 20 years, and TB-related mortality by 22% over 5 years and 50% over 20 years. We found that over a 20-year horizon, TB-specific and HIV-specific programme changes contribute equally to incidence reductions, whereas the TB-specific changes produce a majority of the mortality benefits. An aggressive expansion of ART alongside traditional TB-specific control measures has the potential to greatly reduce TB burden, with the different elements of a combined approach having a synergistic effect in reducing long-term TB incidence and mortality.

  6. Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis.

    PubMed

    Tyagi, Sandeep; Ammerman, Nicole C; Li, Si-Yang; Adamson, John; Converse, Paul J; Swanson, Rosemary V; Almeida, Deepak V; Grosset, Jacques H

    2015-01-20

    A key drug for the treatment of leprosy, clofazimine has recently been associated with highly effective and significantly shortened regimens for the treatment of multidrug-resistant tuberculosis (TB). Consequently, we hypothesized that clofazimine may also shorten the duration of treatment for drug-susceptible TB. We conducted a controlled trial in the mouse model of TB chemotherapy comparing the activity of the 6-mo standard regimen for TB treatment, i.e., 2 mo of daily rifampin, isoniazid, pyrazinamide, and ethambutol followed by 4 mo of rifampin and isoniazid, with a 4-mo clofazimine-containing regimen: 2 mo of daily rifampin, isoniazid, pyrazinamide, and clofazimine followed by 2 mo of rifampin, isoniazid, and clofazimine. Treatment efficacy was assessed on the basis of Mycobacterium tuberculosis colony counts in the lungs and spleens during treatment and on the proportion of mice with culture-positive relapse 6 mo after treatment cessation. No additive effect of clofazimine was observed after the first week of treatment, but, by the second week of treatment, the colony counts were significantly lower in the clofazimine-treated mice than in the mice receiving the standard regimen. Lung culture conversion was obtained after 3 and 5 mo in mice treated with the clofazimine-containing and standard regimens, respectively, and relapse-free cure was obtained after 3 and 6 mo of treatment with the clofazimine-containing and standard regimens, respectively. Thus, clofazimine is a promising anti-TB drug with the potential to shorten the duration of TB chemotherapy by at least half (3 mo vs. 6 mo) in the mouse model of TB. PMID:25561537

  7. Addressing multidrug-resistant tuberculosis in penitentiary hospitals and in the general population of the former Soviet Union.

    PubMed

    Portaels, F; Rigouts, L; Bastian, I

    1999-07-01

    High rates of tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), have been reported from the former Soviet Union. Our laboratory has supported operational studies in jails in Baku, Azerbaijan, and Mariinsk, Siberia. Combining the results from these two penal systems, the rates of MDR-TB among 'newly enrolled' and 'non-responding' cases were 24.6% and 92.1%, respectively. Restriction fragment length polymorphism (RFLP) studies strongly suggest transmission of MDR-TB between prisoners. In Mariinsk, the high rates of MDR-TB have been associated with failure rates of 23%-50% among smear-positive cases receiving fully-supervised standard short-course treatment. There are no coherent guidelines for TB control programmes confronted by high pre-existing levels of MDR-TB but who have only limited laboratory, clinical, pharmaceutical and financial resources. A 'DOTS plus' strategy has been advocated in which an established TB control programme is complemented by facilities to treat MDR-TB patients. However, the exact format of these programmes remains unresolved. Further research is required to describe the natural history of MDR-TB infection, to determine the failure rate of (and the additional resistance induced by) standard short-course treatment when MDR-TB is prevalent, to decide whether standardised or individualised second-line regimens can be employed, and to define the laboratory facilities required by a 'DOTS plus' programme.

  8. Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome.

    PubMed

    Park, Jong Sun; Lee, Jae-Yeon; Lee, Yeon Joo; Kim, Se Joong; Cho, Young-Jae; Yoon, Ho Il; Lee, Choon-Taek; Song, Junghan; Lee, Jae Ho

    2015-10-12

    Therapeutic drug monitoring in tuberculosis remains controversial. We evaluated the relationship between antituberculosis drug levels in blood and clinical outcome. Serum concentrations of first-line antituberculosis drugs were measured in tuberculosis patients between March 2006 and April 2013. Venous blood was drawn 2 h after drug ingestion and was analyzed using high-performance liquid chromatography-tandem mass spectrometry. We retrospectively reviewed the data and determined the association of serum drug levels with clinical outcome. Among 413 patients, the prevalences of low serum concentrations of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA) were 59.9%, 27.8%, 12.8%, and 8.7%, respectively. The low INH group had a greater percentage of patients with a history of tuberculosis treatment (19.2% versus 11.0%; P = 0.026) and was more likely to present with drug-resistant strains (17.6% versus 8.8%; P = 0.049) than the normal INH group; however, low levels of INH, RMP, EMB, and PZA were not related to treatment outcome. Low INH level had a tendency to be associated with 2-month culture positivity, but it was not statistically significant (P = 0.072) in multivariate analysis. Seventeen (4.1%) patients experienced a recurrence. However, the recurrence rate was not statistically different between the low and normal INH groups. Low serum INH may play a role in recurrence and in acquired drug resistance. However, the serum level of INH was not directly related to either treatment response or recurrence rate. The role and usefulness of therapeutic drug monitoring should be evaluated in further prospective studies.

  9. Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

    PubMed Central

    Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

    2012-01-01

    Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

  10. Pharmacokinetics of ofloxacin and levofloxacin for prevention and treatment of multidrug-resistant tuberculosis in children.

    PubMed

    Thee, S; Garcia-Prats, A J; McIlleron, H M; Wiesner, L; Castel, S; Norman, J; Draper, H R; van der Merwe, P L; Hesseling, A C; Schaaf, H S

    2014-05-01

    Limited data on fluoroquinolone pharmacokinetics and cardiac effects in children exist. Among 22 children receiving drug-resistant tuberculosis prophylaxis or treatment, serum concentrations following oral doses of levofloxacin (15 mg/kg of body weight) and ofloxacin (20 mg/kg) were lower than those expected from existing pediatric data, possibly due to differences in the formulations (crushed tablets). Drug exposures were lower than those in adults following standard doses and below the proposed pharmacodynamic targets, likely due to more rapid elimination in children. No QT prolongation was observed.

  11. Treatment regimens for rifampicin-resistant tuberculosis: highlighting a research gap.

    PubMed

    Stagg, H R; Hatherell, H-A; Lipman, M C; Harris, R J; Abubakar, I

    2016-07-01

    Treatment guidance for non-multidrug-resistant (MDR) rifampicin-resistant (RMP-R) tuberculosis (TB) is variable. We aimed to undertake a systematic review and meta-analysis of the randomised controlled trial (RCT) data behind such guidelines to identify the most efficacious treatment regimens. Ovid MEDLINE, the Web of Science and EMBASE were mined using search terms for TB, drug therapy and RCTs. Despite 12 604 records being retrieved, only three studies reported treatment outcomes by regimen for patients with non-MDR RMP-R disease, preventing meta-analysis. Our systematic review highlights a substantial gap in the literature regarding evidence-based treatment regimens for RMP-R TB.

  12. Staff training and ambulatory tuberculosis treatment outcomes: a cluster randomized controlled trial in South Africa.

    PubMed Central

    Lewin, Simon; Dick, Judy; Zwarenstein, Merrick; Lombard, Carl J.

    2005-01-01

    OBJECTIVE: To assess whether adding a training intervention for clinic staff to the usual DOTS strategy (the internationally recommended control strategy for tuberculosis (TB)) would affect the outcomes of TB treatment in primary care clinics with treatment success rates below 70%. METHODS: A cluster randomized controlled trial was conducted from July 1996 to July 2000 in nurse-managed ambulatory primary care clinics in Cape Town, South Africa. Clinics with successful TB treatment completion rates of less than 70% and annual adult pulmonary TB loads of more than 40 patients per year were randomly assigned to either the intervention (n = 12) or control (n = 12) groups. All clinics completed follow-up. Treatment outcomes were measured in cohorts of adult, pulmonary TB patients before the intervention (n = 1200) and 9 months following the training (n = 1177). The intervention comprised an 18-hour experiential, participatory in-service training programme for clinic staff delivered by nurse facilitators and focusing on patient centredness, critical reflection on practice, and quality improvement. The main outcome measure was successful treatment, defined as patients who were cured and those who had completed tuberculosis treatment. FINDINGS: The estimated effect of the intervention was an increase in successful treatment rates of 4.8% (95% confidence interval (CI): -5.5% to 15.2%) and in bacteriological cure rates of 10.4% (CI: -1.2% to 22%). A treatment effect of 10% was envisaged, based on the views of policy-makers on the minimum effect size for large-scale implementation. CONCLUSION: This is the first evidence from a randomized controlled trial on the effects of experiential, participatory training on TB outcomes in primary care facilities in a developing country. Such training did not appear to improve TB outcomes. However, the results were inconclusive and further studies are required. PMID:15868015

  13. FEMALE SEX AND DISCONTINUATION OF ISONIAZID DUE TO ADVERSE EFFECTS DURING THE TREATMENT OF LATENT TUBERCULOSIS

    PubMed Central

    Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.

    2013-01-01

    SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828

  14. [Evaluation of multidrug-resistant tuberculosis treatment in Ivory Coast from 2008 to 2010].

    PubMed

    Ahui, B J-M; Horo, K; Bakayoko, A S; Kouassi, A B; Anon, J C; Brou-Gode, V C; Koffi, M O; Itchy, M V; N'Gom, A S; N'Goran, N B; Aka-Danguy, E

    2013-12-01

    This is a retrospective study conducted from January 2008 to December 2010 on sectional descriptive analysis of records of patients treated for MDR-TB and whose follow-up was in the thoracic department of Centre Hospitalier Universitaire (CHU) of Cocody in Abidjan Côte d'Ivoire. We selected eight patients who met the inclusion criteria of 21 MDR-TB patients registered during the study period. The average age was 29.25years ranging from 21 to 39. Males accounted for 75% of the patients (6 males and 2 females). The students represented the professional social layer most affected with 37.5% of the patients. All patients had a history of tuberculosis and only one patient was HIV positive under anti-retroviral (zidovudin, lamivudin and efavirenz). All cultures found Mycobacterium tuberculosis. The resistance profile in addition to isoniazid and rifampicin, found two cases of resistance to ethambutol and streptomycin. The chest radiograph at the time of initiation of second-line treatment showed essentially excavations in 75% of cases and infiltrates in 25%. The lesions were bilateral in 7 of 8 patients (87.5%). The main side effects observed during treatment were limited to cochleovestibular disorders (2 patients) and neuropsychiatric disorders (2 patients) and digestive disorders in half of the patients with removal of the offending molecule kanamycin. After 24months of treatment, it was numbered five cures (62.5%), two failures and one death.

  15. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection.

    PubMed

    Lönnroth, Knut; Aung, Tin; Maung, Win; Kluge, Hans; Uplekar, Mukund

    2007-05-01

    This article assesses whether social franchising of tuberculosis (TB) services in Myanmar has succeeded in providing quality treatment while ensuring equity in access and financial protection for poor patients. Newly diagnosed TB patients receiving treatment from private general practitioners (GPs) belonging to the franchise were identified. They were interviewed about social conditions, health seeking and health care costs at the time of starting treatment and again after 6 months follow-up. Routine data were used to ascertain clinical outcomes as well as to monitor trends in case notification. The franchisees contributed 2097 (21%) of the total 9951 total new sputum smear-positive pulmonary cases notified to the national TB programme in the study townships. The treatment success rate for new smear-positive cases was 84%, close to the World Health Organization target of 85% and similar to the treatment success of 81% in the national TB programme in Myanmar. People from the lower socio-economic groups represented 68% of the TB patients who access care in the franchise. Financial burden related to direct and indirect health care costs for tuberculosis was high, especially among the poor. Patients belonging to lower socio-economic groups incurred on average costs equivalent to 68% of annual per capita household income, with a median of 28%. However, 83% of all costs were incurred before starting treatment in the franchise, while 'shopping' for care. During treatment in the franchise, the cost of care was relatively low, corresponding to a median proportion of annual per capita income of 3% for people from lower socio-economic groups. This study shows that highly subsidized TB care delivered through a social franchise scheme in the private sector in Myanmar helped reach the poor with quality services, while partly protecting them from high health care expenditure. Extended outreach to others parts of the private sector may reduce diagnostic delay and patient costs

  16. Single-tube nested PCR in the diagnosis of tuberculosis.

    PubMed Central

    Chan, C M; Yuen, K Y; Chan, K S; Yam, W C; Yim, K H; Ng, W F; Ng, M H

    1996-01-01

    AIMS: To evaluate the usefulness of a single-tube nested polymerase chain reaction (PCR) assay in the diagnosis of tuberculosis in 1497 pulmonary and 536 extrapulmonary specimens. METHODS: A single-tube nested PCR, utilising two sets of primers with different melting temperatures (88 degrees C for external primers; 70 degrees C for internal primers) to augment sensitivity and specificity without increasing the risk of amplicon contamination, was evaluated. Specimens were initially tested for the repetitive IS6110 sequences and if negative, retested for the universal 38 kilodalton sequence and for inhibitors. dUTP/Uracil-N-glycosylase and Instagene treatment were used to minimise contamination and the effect of inhibitors, respectively. RESULTS: Using culture as the gold standard, the overall sensitivity of the assay was 89% for pulmonary and 42% for extrapulmonary specimens. Sensitivity varied greatly with respect to sample type (92% for follow up specimens from a chest hospital and 70% for non-follow up specimens from a general hospital). The smear positivity rates were 15% for extrapulmonary specimens, and 69% and 45%, respectively, for follow up and non-follow up specimens from pulmonary sites. Specificity was 99.7%. Inhibitors were present more frequently in extrapulmonary than in pulmonary specimens (13.4% v 2.7%). CONCLUSION: Despite the high sensitivity of the PCR assay for the diagnosis of tuberculosis in pulmonary specimens, it was less effective in the extrapulmonary samples. This is probably because of the lower bacterial load in extrapulmonary specimens, the presence of more inhibitors adversely affecting the PCR assay and the higher volume of specimens used for culture. Images PMID:8655703

  17. Frequency and type of microbiological monitoring of multidrug-resistant tuberculosis treatment.

    PubMed

    Kurbatova, E V; Gammino, V M; Bayona, J; Becerra, M; Danilovitz, M; Falzon, D; Gelmanova, I; Keshavjee, S; Leimane, V; Mitnick, C D; Quelapio, M I D; Riekstina, V; Taylor, A; Viiklepp, P; Zignol, M; Cegielski, J P

    2011-11-01

    Monthly culture is usually recommended to monitor treatment of multidrug-resistant tuberculosis (MDR-TB). As mycobacterial laboratory capacity is limited in many settings, TB programs need evidence to decide whether monthly cultures are necessary compared to other approaches. We simulated three alternative monitoring strategies (culture every 2 or 3 months, and monthly smears alone) in a cohort of MDR-TB patients in Estonia, Latvia, Philippines, Russia and Peru from 2000 to 2004. This retrospective analysis illustrated that less frequent testing delays confirmation of bacteriological conversion. This would prolong intensive treatment, hospitalization and respiratory isolation, increasing cost and toxicity. After conversion, less frequent testing could delay diagnosis of possible treatment failure. PMID:22008772

  18. Children’s Roles in Tuberculosis Treatment Regimes: Constructing childhood and kinship in urban Zambia

    PubMed Central

    Hunleth, Jean

    2013-01-01

    In Zambia, the burden of HIV-related diseases such as tuberculosis has received substantial international attention. Zambians experience and participate in a range of globally produced programs to manage TB and cure TB sufferers. Guided by the WHO’s Directly Observed Treatment, Short-course (DOTS) protocol, TB treatment regimens now emphasize adherence to medications as the primary way to achieve cure. This article aims to understand how adherence models enter into the daily lives of children who live with and care for adult TB patients in an area disproportionately affected by the disease. I suggest that children domesticate adherence models, using them as strategies to safeguard identities, relationships, livelihoods, and futures that are increasingly under threat in the age of HIV. They draw on TB treatment and the hope and agency it affords to hold onto a version of childhood in which they are cared for by adults who will advocate for their wellbeing. PMID:23804398

  19. National tuberculosis programme review: experience over the period 1990-95.

    PubMed Central

    Pio, A.; Luelmo, F.; Kumaresan, J.; Spinaci, S.

    1997-01-01

    Since 1990 the WHO Global Tuberculosis Programme (GTB) has promoted the revision of national tuberculosis programmes to strengthen the focus on directly observed treatment, short-course (DOTS) and close monitoring of treatment outcomes. GTB has encouraged in-depth evaluation of activities through a comprehensive programme review. Over the period 1990-95, WHO supported 12 such programme reviews. The criteria for selection were as follows: large population (Bangladesh, Brazil, China, Ethiopia, India, Indonesia, Mexico, and Thailand); good prospects of developing a model programme for a region (Nepal, Zimbabwe); or at advanced stage of implementation of a model programme for a region (Guinea, Peru). The estimated combined incidence of smear-positive pulmonary tuberculosis was 82 per 100,000 population, about 43% of the global incidence. The prevalence of infection with human immunodeficiency virus (HIV) was variable, being very high in Ethiopia and Zimbabwe, but negligible in Bangladesh, China, Nepal and Peru. The programme reviews were conducted by teams of 15-35 experts representing a wide range of national and external institutions. After a 2-3-month preparatory period, the conduct of the review usually lasted 2-3 weeks, including a first phase of meetings with authorities and review of documents, a second phase for field visits, and a third phase of discussion of findings and recommendations. The main lessons learned from the programme reviews were as follows: programme review is a useful tool to secure government commitment, reorient the tuberculosis control policies and replan the activities on solid grounds; the involvement of public health and academic institutions, cooperating agencies, and nongovernmental organizations secured a broad support to the new policies; programme success is linked to a centralized direction which supports a decentralized implementation through the primary health care services; monitoring and evaluation of case management functions

  20. Bedaquiline for the treatment of multidrug-resistant tuberculosis: great promise or disappointment?

    PubMed

    Field, Stephen K

    2015-07-01

    Acquired drug resistance by Mycobacterium tuberculosis (MTB) may result in treatment failure and death. Bedaquiline was recently approved for the treatment of multidrug-resistant tuberculosis (MDR-TB). This report examines the available data on this novel drug for the treatment of MDR-TB. PubMed searches, last updated 18 February 2015, using the terms bedaquiline, TMC 207 and R207910 identified pertinent English citations. Citation reference lists were reviewed to identify other relevant reports. Pertinent MDR-TB treatment reports on the US Food and Drug Administration, Centers for Disease Control and Prevention (CDC), World Health Organization (WHO) and Cochrane websites were also evaluated. Bedaquiline is an adenosine triphosphate (ATP) synthase inhibitor specific for MTB and some nontuberculous mycobacteria. The early bactericidal activity (EBA) of bedaquiline is delayed until ATP stores are depleted but subsequently it is similar to the EBA of isoniazid and rifampin. Bedaquiline demonstrated excellent minimum inhibitory concentrations (MICs) against both drug-sensitive and MDR-TB. Adding it to the WHO-recommended MDR-TB regimen reduced the time for sputum culture conversion in pulmonary MDR-TB. Rifampin, other cytochrome oxidase 3A4 inducers or inhibitors alter its metabolism. Adverse effects are common with MDR-TB treatment regimens with or without bedaquiline. Nausea is more common with bedaquiline and it increases the QTcF interval. It is not recommended for children, pregnant or lactating women. More patients died in the bedaquiline-treatment arms despite better microbiological outcomes in two recent trials. The WHO and CDC published interim guidelines that recommend restricting its use to patients with MDR-TB or more complex drug resistance who cannot otherwise be treated with a minimum of three effective drugs. It should never be added to a regimen as a single drug nor should it be added to a failing regimen to prevent the emergence of bedaquiline

  1. Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis--A Review.

    PubMed

    da Silva, Patricia Bento; de Freitas, Eduardo Sinésio; Bernegossi, Jessica; Gonçalez, Maíra Lima; Sato, Mariana Rillo; Leite, Clarice Queico Fujimura; Pavan, Fernando Rogério; Chorilli, Marlus

    2016-02-01

    Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB.

  2. [Commemorative lecture of receiving Imamura Memorial Prize. Studies on prevention and treatment of childhood tuberculosis].

    PubMed

    Takamatsu, I

    1999-11-01

    We performed a retrospective analysis of 394 patients who were treated for active tuberculosis (TB) at our hospital from 1976 to 1997. We had started early BCG vaccination campaign in Osaka Prefecture from 1995 and the coverage of BCG vaccination in infants rose up to about 90%. From that experience, we studied the current situations and measures on prevention and treatment of childhood tuberculosis. Pulmonary TB in children is successfully treated with 6-month standard short-course chemotherapy using isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin daily for 4 months. Prognosis of childhood tuberculous meningitis (TBM) is poor, early diagnosis and prevention of TBM is important. In order to promote TB control and eliminate childhood TB, especially in infants, the following is necessary; 1) early detection and treatment of adult TB patients, source of infection, 2) prompt and appropriate contact examination and chemoprophylaxis, 3) BCG vaccination during early infancy, 4) protection from MDR-TB are most important.

  3. Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis--A Review.

    PubMed

    da Silva, Patricia Bento; de Freitas, Eduardo Sinésio; Bernegossi, Jessica; Gonçalez, Maíra Lima; Sato, Mariana Rillo; Leite, Clarice Queico Fujimura; Pavan, Fernando Rogério; Chorilli, Marlus

    2016-02-01

    Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB. PMID:27305759

  4. [Commemorative lecture of receiving Imamura Memorial Prize. Studies on prevention and treatment of childhood tuberculosis].

    PubMed

    Takamatsu, I

    1999-11-01

    We performed a retrospective analysis of 394 patients who were treated for active tuberculosis (TB) at our hospital from 1976 to 1997. We had started early BCG vaccination campaign in Osaka Prefecture from 1995 and the coverage of BCG vaccination in infants rose up to about 90%. From that experience, we studied the current situations and measures on prevention and treatment of childhood tuberculosis. Pulmonary TB in children is successfully treated with 6-month standard short-course chemotherapy using isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin daily for 4 months. Prognosis of childhood tuberculous meningitis (TBM) is poor, early diagnosis and prevention of TBM is important. In order to promote TB control and eliminate childhood TB, especially in infants, the following is necessary; 1) early detection and treatment of adult TB patients, source of infection, 2) prompt and appropriate contact examination and chemoprophylaxis, 3) BCG vaccination during early infancy, 4) protection from MDR-TB are most important. PMID:10599214

  5. Unusual sex differences in tuberculosis notifications across Pakistan and the role of environmental factors.

    PubMed

    Khan, M S; Khan, M S; Hasan, R; Godfrey-Faussett, P

    2013-09-01

    In developing countries, only one-third of new tuberculosis cases notified are from women. It is not clear whether tuberculosis incidence is lower in women than men, or whether notification figures reflect under-detection of tuberculosis in women. Pakistan, however, presents an unusual pattern of sex differences in tuberculosis notifications. While 2 of the 4 provinces (Sindh and Punjab) report more notifications from men (female to male ratios 0.81 and 0.89 respectively in 2009), the other 2 provinces (Khyber-Pakhtunkhwa and Balochistan) consistently report higher numbers of smear-positive tuberculosis notifications from women than men (1.37 and 1.40). No other country is known to have such a large variation in the sex ratios of notifications across regions. Large variations in female to male smear-positive notification ratios in different settings across a single country may indicate that environmental factors, rather than endogenous biological factors, are important in influencing the observed sex differences in tuberculosis notifications.

  6. [Tuberculosis control in Malawi. Time distribution of cessation of treatment and proposals for reorientation of the program].

    PubMed

    Lehingue, Y; Urtizberea, J A

    1986-01-01

    In Kasungu district (Malaŵi), the patients with pulmonary tuberculosis are admitted in the district hospital for two months and then referred to the private organization LEPRA for further ambulatory treatment. Out of 73 patients found with positive expectoration for AAFB during 8 months, 54 were actually referred to LEPRA, 4 were sent to another hospital on died, and 15 defaulted. Later on 15% of the patients referred to LEPRA were lost to follow up during one year. 2/3 of defaulting happened during the 2 first months of the treatment. Furthermore the infectious patients case finding rate is likely to be very low. Those observations lead to propose three prioritary actions to improve tuberculosis control: case finding amelioration, relinquishment of compulsory long duration admissions, and integration of the tuberculosis care network into the general health system.

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

    PubMed

    Jenkins, Helen E; Crudu, Valeriu; Soltan, Viorel; Ciobanu, Ana; Domente, Liliana; Cohen, Ted

    2014-04-01

    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.

  8. Treatment paradox in musculo-skeletal tuberculosis in an immunocompetent adult male; a case report from a tertiary care hospital.

    PubMed

    Chaskar, Priyanka; Rana, Geetika; Anuradha; Duggal, Nandini; Arora, Jyoti

    2015-04-01

    Paradoxical reactions like immune reconstitution inflammatory syndrome (IRIS) as seen with patients on retroviral treatment in HIV infection, have also been identified in HIV sero-negative patients with extra pulmonary tuberculosis especially lymph-node tuberculosis. Musculo-skeletal tuberculosis presenting as a cold abscess of the anterior chest wall is a rare entity which poses diagnostic and therapeutic challenge. A 35-year-old immunocompetent male came with complains of painless lump on right side of his chest over 9th and 10th intercostal space which gradually increased and extended upto 11th rib area. Clinically, diagnosis of cold abscess was made and anti-tubercular therapy (ATT) was started. Despite of being on ATT for 3 weeks, patient developed pain and signs of inflammation. Fluid was aspirated and sent for biochemical and microbiological investigations. The aspirated fluid was positive for acid fast bacilli by ZN stain and grew Mycobacterium tuberculosis in culture, sensitive to first line ATT. Pyogenic and fungal culture was negative. This case presented as an anterior chest wall cold abscess which deteriorated on initiation of first line ATT, thus creating a suspicion of resistance to ATT which was cleared on ATT susceptibility testing. Hence, this case underlines the possibility of treatment paradoxes seen in immunocompetent musculo-skeletal tuberculosis. PMID:26046019

  9. Assessment of treatment interruption among pulmonary tuberculosis patients: A cross-sectional study

    PubMed Central

    Gorityala, Satya Bhgath; Mateti, Uday Venkat; Konuru, Venkateswarlu; Martha, Srinivas

    2015-01-01

    Background: Multi-drug resistant tuberculosis (TB) is a rising peril of the TB control in India caused mostly by incomplete treatment. Aim: The aim was to assess the treatment interruption among pulmonary TB (PTB) patients. Materials and Methods: A cross-sectional study was carried out for a period of 9 months among PTB patients. Patients admitted with active pulmonary Koch's and history of anti-TB treatment (ATT) for 1-month or more from any source and who returns to treatment after not taking ATT consecutively for 2 months or more were included in the study. The data were collected from the patients or their caretakers to obtain the source of treatment given previously before default, number of treatment interruptions, phase and reasons for treatment interruption treatment. Results: A total of 107 defaulters were identified during the study period. In the present study, 62.6% of the patients interrupted treatment only once, 55.34% of the patient's early continuation (3–4 months) treatment, and 47.66% of the patient's only one reason for the treatment interruptions during the course of the treatment. The most common reason for the treatment interruptions were felt well with TB treatment (29.53%) followed by side effects (16.06%), lack of money (8.29%), and other reasons. Conclusion: The study revealed that most of the defaulters were in the age group between 35 and 60 years, male gender, illiterates, daily wage labor, and married. The treatment interruptions were minimized by putting the efforts to improve direct supervision; pretreatment counseling and retrieve treatment interrupters were recommended. PMID:26229358

  10. Differences between Risk Factors Associated with Tuberculosis Treatment Abandonment and Mortality

    PubMed Central

    Gomes, Nathália Mota de Faria; Bastos, Meire Cardoso da Mota; Marins, Renata Magliano; Barbosa, Aline Alves; Soares, Luiz Clóvis Parente; de Abreu, Annelise Maria de Oliveira Wilken; Souto Filho, João Tadeu Damian

    2015-01-01

    Objectives. To identify the risk factors that were associated with abandonment of treatment and mortality in tuberculosis (TB) patients. Methods. This study was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2002 and 2008 in a TB reference center. Results. A total of 1,257 patients were evaluated, with 69.1% men, 54.4% under 40 years of age, 18.9% with extrapulmonary disease, and 9.3% coinfected with HIV. The risk factors that were associated with abandonment of treatment included male gender (OR = 2.05; 95% CI = 1.15–3.65) and nonadherence to previous treatment (OR = 3.14; 95% CI = 1.96–5.96). In addition, the presence of extrapulmonary TB was a protective factor (OR = 0.33, 95% CI = 0.14–0.76). The following risk factors were associated with mortality: age over 40 years (OR = 2.61, 95% CI = 1.76–3.85), coinfection with HIV (OR = 6.01, 95% CI = 3.78–9.56), illiteracy (OR = 1.88, 95% CI = 1.27–2.75), the presence of severe extrapulmonary TB (OR = 2.33, 95% CI = 1.24–4.38), and retreatment after relapse (OR = 1.95, 95% CI = 1.01–3.75). Conclusions. Male gender and retreatment after abandonment were independent risk factors for nonadherence to TB treatment. Furthermore, age over 40 years, coinfection with HIV, illiteracy, severe extrapulmonary TB, and retreatment after relapse were associated with higher TB mortality. Therefore, we suggest the implementation of direct measures that will control the identified risk factors to reduce the rates of treatment failure and TB-associated mortality. PMID:26600948

  11. Dry powder PA-824 aerosols for treatment of tuberculosis in guinea pigs.

    PubMed

    Garcia-Contreras, Lucila; Sung, Jean C; Muttil, Pavan; Padilla, Danielle; Telko, Martin; Verberkmoes, Jarod L; Elbert, Katharina J; Hickey, Anthony J; Edwards, David A

    2010-04-01

    Novel treatments for multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB), or latent TB are needed urgently. Recently, we reported the formulation and characterization of the nitroimidazo-oxazine PA-824 for efficient aerosol delivery as dry powder porous particles and the subsequent disposition in guinea pigs after pulmonary administration. The objective of the present study was to evaluate the effects of these PA-824 therapeutic aerosols on the extent of TB infection in the low-inoculum aerosol infection guinea pig model. Four weeks after infection by the pulmonary route, animals received daily treatment for 4 weeks of either a high or a low dose of PA-824 dry powder aerosol. Animals received PA-824 cyclodextrin/lecithin suspensions orally as positive controls, and those receiving placebo particles or no treatment were negative controls. The lungs and spleens of animals receiving the high dose of inhaled PA-824 particles exhibited a lower degree of inflammation (indicated by wet tissue weights), bacterial burden, and tissue damage (indicated by histopathology) than those of untreated or placebo animals. Treatment with oral PA-824 cyclodextrin/lecithin suspension resulted in a more significant reduction in the bacterial burden of lungs and spleen, consistent with a dose that was larger than inhaled doses (eight times the inhaled low dose and four times the inhaled high dose). However, histopathological analysis revealed that the extent of tissue damage was comparable in groups receiving the oral or either inhaled dose. The present studies indicate the potential use of PA-824 dry powder aerosols in the treatment of TB.

  12. [Tuberculosis in the Czech Republic. Current status. Diagnosis, treatment and prevention].

    PubMed

    Vašáková, M

    2013-04-01

    Despite the fact that the tuberculosis (TB) agent, Mycobacterium tuberculosis, was discovered more than a century ago and we have had a basic drug line for the treatment of this disease available for over 50 years, TB is still a worldwide threat, be it considering the number of the infected, or their mortality. The epidemiologic seriousness of this disease lies, however, in the chronic course of the illness, the length of time necessary for its treatment, unavailable preventative measures and the treatment in those parts of world that are stricken by hunger and poverty. The situation concerning TB in the Czech Republic (CR) is much more optimistic; the number of new cases is still decreasing. However, in order to keep the decreasing trend of new cases it is necessary to keep TB in mind so that diagnosis, isolation and treatment of TB patients occur in a timely manner. Since TB affects mainly people with low income and low social status, or patients exposed to specific treatment methods, it is essential for the prevention to be focused especially on these people and social groups. BCG vaccination in CR is selective since 2011; i.e. only high risk infants are vaccinated. Nevertheless, the BCG vaccine provides only an incomplete and highly variable TB protection and, moreover, it has severe adverse effects. Therefore, there has been an attempt to develop a new vaccine. Hand- in hand with the development of a new vaccine, there has been an attempt to synthesize new and more effective antituberculotics that would affect even multiresistant tubercle bacilli. PMID:23711054

  13. Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis.

    PubMed

    Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W

    2016-07-01

    Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment.

  14. Life experiences of patients who have completed tuberculosis treatment: a qualitative investigation in southeast Brazil

    PubMed Central

    2013-01-01

    Background Despite being curable, tuberculosis is still a stigmatized disease. Not only is TB patients’ suffering due to its clinical manifestations, but also because of society’s prejudice, embarrassing situations, and even self-discrimination. This study aims to investigate psychosocial experiences of patients who have completed tuberculosis treatment in São Carlos a municipality in the interior of São Paulo State, Brazil. Methods This study, of a clinical-qualitative nature, sought to understand the meanings provided by the participants themselves. Fifteen individuals, who had successfully completed tuberculosis treatment, participated in this research. The sample size was established using the information saturation criterion. Data were collected by means of interviews with in-depth open-ended questions. Data were treated by categorizing and analyzing content according to themes. Results Regardless of all progress, this study found that TB still causes patients to suffer from fear of transmission, social prejudice, and death. Despite the fact that the emotional support provided by families and healthcare professionals is considered essential to treatment adherence and completion, participants in this study reveal that friends and colleagues have distanced themselves from them for fear of contagion and/or prejudice. Ignorance about the disease and its transmission modes can be found in the interviewees’ statements, which seems to indicate that they have become vectors of transmission of stigma themselves. Patients’ medical leave from work during treatment may be due to both their health conditions and their attempt to avoid social/emotional embarrassment. There are accounts that TB has caused psychosocial damage to patients’ lives and that they feel more fatigue and lassitude and have begun to pay more attention to their own health. Conclusions Healthcare workers should be aware of the ways TB treatment affect patients’ psychosocial life and

  15. Risk factors for the development of non-response to first-line treatment for tuberculosis in southern Vietnam.

    PubMed

    Keane, V P; de Klerk, N; Krieng, T; Hammond, G; Musk, A W

    1997-10-01

    Since 1979, the International Organization for Migration has provided tuberculosis screening and treatment for those who intend to migrate from Viet Nam--a country with one of the highest tuberculosis incidence rates. The factors associated with non-response to first-line tuberculosis treatment were investigated in a comparative study of 130 non-responders (cases) and 673 responders (controls). Cases had worse radiologic signs and greater numbers of acid-fast bacilli on their sputum smears than controls. When these two factors were used as a diagnostic test to predict non-response, the model had a sensitivity of 70% and a specificity of 80%. Sensitivity increased to 80% when variables measured in the first 3 months of treatment were used. Failure to respond to treatment can be a result of infection with other mycobacteria, infection with a multi-drug resistant tuberculosis strain, or acquisition of resistance after the initiation of therapy. Further analysis of the same database is underway to determine the natural history and success of second-line treatment.

  16. Risk factors for the development of non-response to first-line treatment for tuberculosis in southern Vietnam.

    PubMed

    Keane, V P; de Klerk, N; Krieng, T; Hammond, G; Musk, A W

    1997-10-01

    Since 1979, the International Organization for Migration has provided tuberculosis screening and treatment for those who intend to migrate from Viet Nam--a country with one of the highest tuberculosis incidence rates. The factors associated with non-response to first-line tuberculosis treatment were investigated in a comparative study of 130 non-responders (cases) and 673 responders (controls). Cases had worse radiologic signs and greater numbers of acid-fast bacilli on their sputum smears than controls. When these two factors were used as a diagnostic test to predict non-response, the model had a sensitivity of 70% and a specificity of 80%. Sensitivity increased to 80% when variables measured in the first 3 months of treatment were used. Failure to respond to treatment can be a result of infection with other mycobacteria, infection with a multi-drug resistant tuberculosis strain, or acquisition of resistance after the initiation of therapy. Further analysis of the same database is underway to determine the natural history and success of second-line treatment. PMID:9363535

  17. Spatio-Temporal Distribution Characteristics and Trajectory Similarity Analysis of Tuberculosis in Beijing, China.

    PubMed

    Li, Lan; Xi, Yuliang; Ren, Fu

    2016-03-01

    Tuberculosis (TB) is an infectious disease with one of the highest reported incidences in China. The detection of the spatio-temporal distribution characteristics of TB is indicative of its prevention and control conditions. Trajectory similarity analysis detects variations and loopholes in prevention and provides urban public health officials and related decision makers more information for the allocation of public health resources and the formulation of prioritized health-related policies. This study analysed the spatio-temporal distribution characteristics of TB from 2009 to 2014 by utilizing spatial statistics, spatial autocorrelation analysis, and space-time scan statistics. Spatial statistics measured the TB incidence rate (TB patients per 100,000 residents) at the district level to determine its spatio-temporal distribution and to identify characteristics of change. Spatial autocorrelation analysis was used to detect global and local spatial autocorrelations across the study area. Purely spatial, purely temporal and space-time scan statistics were used to identify purely spatial, purely temporal and spatio-temporal clusters of TB at the district level. The other objective of this study was to compare the trajectory similarities between the incidence rates of TB and new smear-positive (NSP) TB patients in the resident population (NSPRP)/new smear-positive TB patients in the TB patient population (NSPTBP)/retreated smear-positive (RSP) TB patients in the resident population (RSPRP)/retreated smear-positive TB patients in the TB patient population (RSPTBP) to detect variations and loopholes in TB prevention and control among the districts in Beijing. The incidence rates in Beijing exhibited a gradual decrease from 2009 to 2014. Although global spatial autocorrelation was not detected overall across all of the districts of Beijing, individual districts did show evidence of local spatial autocorrelation: Chaoyang and Daxing were Low-Low districts over the six

  18. Spatio-Temporal Distribution Characteristics and Trajectory Similarity Analysis of Tuberculosis in Beijing, China

    PubMed Central

    Li, Lan; Xi, Yuliang; Ren, Fu

    2016-01-01

    Tuberculosis (TB) is an infectious disease with one of the highest reported incidences in China. The detection of the spatio-temporal distribution characteristics of TB is indicative of its prevention and control conditions. Trajectory similarity analysis detects variations and loopholes in prevention and provides urban public health officials and related decision makers more information for the allocation of public health resources and the formulation of prioritized health-related policies. This study analysed the spatio-temporal distribution characteristics of TB from 2009 to 2014 by utilizing spatial statistics, spatial autocorrelation analysis, and space-time scan statistics. Spatial statistics measured the TB incidence rate (TB patients per 100,000 residents) at the district level to determine its spatio-temporal distribution and to identify characteristics of change. Spatial autocorrelation analysis was used to detect global and local spatial autocorrelations across the study area. Purely spatial, purely temporal and space-time scan statistics were used to identify purely spatial, purely temporal and spatio-temporal clusters of TB at the district level. The other objective of this study was to compare the trajectory similarities between the incidence rates of TB and new smear-positive (NSP) TB patients in the resident population (NSPRP)/new smear-positive TB patients in the TB patient population (NSPTBP)/retreated smear-positive (RSP) TB patients in the resident population (RSPRP)/retreated smear-positive TB patients in the TB patient population (RSPTBP) to detect variations and loopholes in TB prevention and control among the districts in Beijing. The incidence rates in Beijing exhibited a gradual decrease from 2009 to 2014. Although global spatial autocorrelation was not detected overall across all of the districts of Beijing, individual districts did show evidence of local spatial autocorrelation: Chaoyang and Daxing were Low-Low districts over the six

  19. Spatio-Temporal Distribution Characteristics and Trajectory Similarity Analysis of Tuberculosis in Beijing, China.

    PubMed

    Li, Lan; Xi, Yuliang; Ren, Fu

    2016-03-07

    Tuberculosis (TB) is an infectious disease with one of the highest reported incidences in China. The detection of the spatio-temporal distribution characteristics of TB is indicative of its prevention and control conditions. Trajectory similarity analysis detects variations and loopholes in prevention and provides urban public health officials and related decision makers more information for the allocation of public health resources and the formulation of prioritized health-related policies. This study analysed the spatio-temporal distribution characteristics of TB from 2009 to 2014 by utilizing spatial statistics, spatial autocorrelation analysis, and space-time scan statistics. Spatial statistics measured the TB incidence rate (TB patients per 100,000 residents) at the district level to determine its spatio-temporal distribution and to identify characteristics of change. Spatial autocorrelation analysis was used to detect global and local spatial autocorrelations across the study area. Purely spatial, purely temporal and space-time scan statistics were used to identify purely spatial, purely temporal and spatio-temporal clusters of TB at the district level. The other objective of this study was to compare the trajectory similarities between the incidence rates of TB and new smear-positive (NSP) TB patients in the resident population (NSPRP)/new smear-positive TB patients in the TB patient population (NSPTBP)/retreated smear-positive (RSP) TB patients in the resident population (RSPRP)/retreated smear-positive TB patients in the TB patient population (RSPTBP) to detect variations and loopholes in TB prevention and control among the districts in Beijing. The incidence rates in Beijing exhibited a gradual decrease from 2009 to 2014. Although global spatial autocorrelation was not detected overall across all of the districts of Beijing, individual districts did show evidence of local spatial autocorrelation: Chaoyang and Daxing were Low-Low districts over the six

  20. Economic support to improve tuberculosis treatment outcomes in South Africa: a pragmatic cluster-randomized controlled trial

    PubMed Central

    2013-01-01

    Background Poverty undermines adherence to tuberculosis treatment. Economic support may both encourage and enable patients to complete treatment. In South Africa, which carries a high burden of tuberculosis, such support may improve the currently poor outcomes of patients on tuberculosis treatment. The aim of this study was to test the feasibility and effectiveness of delivering economic support to patients with pulmonary tuberculosis in a high-burden province of South Africa. Methods This was a pragmatic, unblinded, two-arm cluster-randomized controlled trial, where 20 public sector clinics acted as clusters. Patients with pulmonary tuberculosis in intervention clinics (n = 2,107) were offered a monthly voucher of ZAR120.00 (approximately US$15) until the completion of their treatment. Vouchers were redeemed at local shops for foodstuffs. Patients in control clinics (n = 1,984) received usual tuberculosis care. Results Intention to treat analysis showed a small but non-significant improvement in treatment success rates in intervention clinics (intervention 76.2%; control 70.7%; risk difference 5.6% (95% confidence interval: -1.2%, 12.3%), P = 0.107). Low fidelity to the intervention meant that 36.2% of eligible patients did not receive a voucher at all, 32.3% received a voucher for between one and three months and 31.5% received a voucher for four to eight months of treatment. There was a strong dose–response relationship between frequency of receipt of the voucher and treatment success (P <0.001). Conclusions Our pragmatic trial has shown that, in the real world setting of public sector clinics in South Africa, economic support to patients with tuberculosis does not significantly improve outcomes on treatment. However, the low fidelity to the delivery of our voucher meant that a third of eligible patients did not receive it. Among patients in intervention clinics who received the voucher at least once, treatment success rates were significantly

  1. A Novel Inhibitor of Gyrase B Is a Potent Drug Candidate for Treatment of Tuberculosis and Nontuberculosis Mycobacterial Infections

    PubMed Central

    Jones, Steven M.; Hanzelka, Brian L.; Perola, Emanuele; Shoen, Carolyn M.; Cynamon, Michael H.; Ngwane, Andile H.; Wiid, Ian J.; van Helden, Paul D.; Betoudji, Fabrice; Nuermberger, Eric L.; Thomson, John A.

    2014-01-01

    New drugs to treat drug-resistant tuberculosis are urgently needed. Extensively drug-resistant and probably the totally drug-resistant tuberculosis strains are resistant to fluoroquinolones like moxifloxacin, which target gyrase A, and most people infected with these strains die within a year. In this study, we found that a novel aminobenzimidazole, VXc-486, which targets gyrase B, potently inhibits multiple drug-sensitive isolates and drug-resistant isolates of Mycobacterium tuberculosis in vitro (MICs of 0.03 to 0.30 μg/ml and 0.08 to 5.48 μg/ml, respectively) and reduces mycobacterial burdens in lungs of infected mice in vivo. VXc-486 is active against drug-resistant isolates, has bactericidal activity, and kills intracellular and dormant M. tuberculosis bacteria in a low-oxygen environment. Furthermore, we found that VXc-486 inhibits the growth of multiple strains of Mycobacterium abscessus, Mycobacterium avium complex, and Mycobacterium kansasii (MICs of 0.1 to 2.0 μg/ml), as well as that of several strains of Nocardia spp. (MICs of 0.1 to 1.0 μg/ml). We made a direct comparison of the parent compound VXc-486 and a phosphate prodrug of VXc-486 and showed that the prodrug of VXc-486 had more potent killing of M. tuberculosis than did VXc-486 in vivo. In combination with other antimycobacterial drugs, the prodrug of VXc-486 sterilized M. tuberculosis infection when combined with rifapentine-pyrazinamide and bedaquiline-pyrazinamide in a relapse infection study in mice. Furthermore, the prodrug of VXc-486 appeared to perform at least as well as the gyrase A inhibitor moxifloxacin. These findings warrant further development of the prodrug of VXc-486 for the treatment of tuberculosis and nontuberculosis mycobacterial infections. PMID:25534737

  2. Factors affecting treatment outcomes in drug-resistant tuberculosis cases in the Northern Cape, South Africa.

    PubMed

    Elliott, E; Draper, H R; Baitsiwe, P; Claassens, M M

    2014-09-21

    The Northern Cape Province has low cure rates (21%) for multidrug-resistant tuberculosis (TB). We audited the programme to identify factors affecting treatment outcomes. Cases admitted to two drug-resistant TB units from 2007 to 2009 had data extracted from clinical folders. Unfavourable treatment outcomes were found in 58% of the 272 cases. A multivariable regression analysis found that male sex was associated with unfavourable outcome (P = 0.009). Weight at diagnosis (P < 0.001) and oral drug adherence (P < 0.001) were also associated with an unfavourable outcome; however, injectable drug adherence was not (P = 0.395). Positive baseline smear and human immunodeficiency virus positive status were not associated with unfavourable outcome. Shorter, more patient-friendly regimens may go a long way to improving adherence and outcomes.

  3. Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research

    PubMed Central

    Munro, Salla A; Lewin, Simon A; Smith, Helen J; Engel, Mark E; Fretheim, Atle; Volmink, Jimmy

    2007-01-01

    Background Tuberculosis (TB) is a major contributor to the global burden of disease and has received considerable attention in recent years, particularly in low- and middle-income countries where it is closely associated with HIV/AIDS. Poor adherence to treatment is common despite various interventions aimed at improving treatment completion. Lack of a comprehensive and holistic understanding of barriers to and facilitators of, treatment adherence is currently a major obstacle to finding effective solutions. The aim of this systematic review of qualitative studies was to understand the factors considered important by patients, caregivers and health care providers in contributing to TB medication adherence. Methods and Findings We searched 19 electronic databases (1966–February 2005) for qualitative studies on patients', caregivers', or health care providers' perceptions of adherence to preventive or curative TB treatment with the free text terms “Tuberculosis AND (adherence OR compliance OR concordance)”. We supplemented our search with citation searches and by consulting experts. For included studies, study quality was assessed using a predetermined checklist and data were extracted independently onto a standard form. We then followed Noblit and Hare's method of meta-ethnography to synthesize the findings, using both reciprocal translation and line-of-argument synthesis. We screened 7,814 citations and selected 44 articles that met the prespecified inclusion criteria. The synthesis offers an overview of qualitative evidence derived from these multiple international studies. We identified eight major themes across the studies: organisation of treatment and care; interpretations of illness and wellness; the financial burden of treatment; knowledge, attitudes, and beliefs about treatment; law and immigration; personal characteristics and adherence behaviour; side effects; and family, community, and household support. Our interpretation of the themes across all

  4. Benzothiazinethione is a potent preclinical candidate for the treatment of drug-resistant tuberculosis

    PubMed Central

    Gao, Chao; Peng, Cuiting; Shi, Yaojie; You, Xinyu; Ran, Kai; Xiong, Lu; Ye, Ting-hong; Zhang, Lidan; Wang, Ningyu; Zhu, Yongxia; Liu, Kun; Zuo, Weiqiong; Yu, Luoting; Wei, Yuquan

    2016-01-01

    New chemotherapeutic compounds are needed to combat multidrug-resistant Mycobacterium tuberculosis (Mtb), which remains a serious public-health challenge. Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1 enzyme) has been characterized as an attractive therapeutic target to address this urgent demand. Herein, we have identified a new class of DprE1 inhibitors benzothiazinethiones as antitubercular agents. Benzothiazinethione analogue SKLB-TB1001 exhibited excellent activity against Mtb in the Microplate Alamar blue assay and intracellular model, meanwhile SKLB-TB1001 was also highly potent against multi-drug resistant extensively and drug resistant clinical isolates. Importantly, no antagonism interaction was found with any two-drug combinations tested in the present study and the combination of SKLB-TB1001 with rifampicin (RMP) was proved to be synergistic. Furthermore, benzothiazinethione showed superb in vivo antitubercular efficacy in an acute Mtb infection mouse model, significantly better than that of BTZ043. These data combined with the bioavailability and safety profiles of benzothiazinethione indicates SKLB-TB1001 is a promising preclinical candidate for the treatment of drug-resistant tuberculosis. PMID:27405961

  5. Tuberculosis in humans and its epidemiology, diagnosis and treatment in the United States.

    PubMed

    LoBue, P A; Enarson, D A; Thoen, T C

    2010-10-01

    Tuberculosis (TB) is a pulmonary and systemic disease caused by Mycobacterium tuberculosis complex species. TB is spread from person to person by airborne transmission. Several factors determine the probability of transmission, including the infectiousness of the source patient and the nature of the environment where exposure occurs. This initial infection (primary TB) rapidly progresses to disease in some persons (especially children and immunocompromised persons), but resolves spontaneously in most individuals. This condition in which the organism lies dormant is known as latent TB infection (LTBI). In the United States, the diagnosis of LTBI is made with either the tuberculin skin test or an interferon-gamma release assay. LTBI is treated with isoniazid (INH; usually for 9 months) to prevent progression to TB disease. Up to 5% of immunocompetent persons will progress to TB disease at some time in the future, even decades after infection, if they are not treated for LTBI. Pulmonary TB disease is diagnosed using a combination of chest radiography and microscopic examination, culture and nucleic acid amplification testing of sputum. Treatment of drug-susceptible TB consists of at least 6 months of an INH and rifampin-containing regimen (with ethambutol and pyrazinamide for the first 2 months). In the United States, drug-resistant TB is relatively rare (approximately 1% of all patients), and is treated with an 18-24 month individualized regimen based on drug susceptibility test results.

  6. Is real-time PCR better than conventional PCR for Mycobacterium tuberculosis complex detection in clinical samples?

    PubMed

    Tortoli, Enrico; Urbano, Pasquale; Marcelli, Fiorella; Simonetti, Tullia M; Cirillo, Daniela M

    2012-08-01

    Cobas Amplicor MTB and later Cobas TaqMan MTB were used to test a very large series of consecutive specimens received for tuberculosis diagnosis. Performance parameters were estimated and compared overall and for separate specimen categories. Both systems showed excellent specificity, and that of TaqMan was the higher. The sensitivities were similar but satisfactory only with respiratory specimens and smear-positive samples.

  7. [Possibilities of intravenous use of helium-neon laser in the treatment of experimental tuberculosis of animals].

    PubMed

    Topol'nitskiĭ, V G; Maliev, B M; Gracheva, M P; Kruglova, E G

    1992-01-01

    The study presents experimental finding of 40 mongrel dogs whose intravascular blood was irradiated with laser as a supplement to the multimodality treatment of respiratory tuberculosis. Earlier disappearance of intoxication symptoms and reduced terms of destruction cavity decrease and closure, as roentgenologically evidenced, was achieved. The influence of this treatment on certain lipid peroxidation parameters, hemocoagulation, immunity status and bacteriostatic blood activity were found. There were no side effects during treatment. PMID:1409508

  8. Factors that influence treatment adherence of tuberculosis patients living in Java, Indonesia

    PubMed Central

    Widjanarko, Bagoes; Gompelman, Michelle; Dijkers, Maartje; van der Werf, Marieke J

    2009-01-01

    Background and objective: Due to nonadherence of tuberculosis (TB) patients to treatment, complications may arise and if remaining infectious, these patients may infect other people with TB. To obtain information about factors associated with nonadherence, we performed a study comparing adherent and nonadherent TB patients. Methods: Adherent and nonadherent patients randomly selected from hospital records in one urban and two rural districts were interviewed using semi-structured questionnaires. Key informant interviews were done with TB nurses and doctors. Results: The most frequently mentioned reason for nonadherence to treatment was feeling better. Although the drugs were given free of charge, many patients were nonadherent because of lack of money. Social support was considered very important for adherence. The study indicated that some patients had a negative image about the health care staff, treatment, and quality of medication. Conclusion: Treatment adherence of TB patients receiving treatment in hospitals in Central Java might be improved by providing health education about treatment duration and side effects, facilitating procedures for receiving treatment free of charge and reducing costs of transportation and consultation. Qualified friendly health care staff able to motivate patients might further improve adherence. PMID:19936166

  9. Within patient microevolution of Mycobacterium tuberculosis correlates with heterogeneous responses to treatment

    PubMed Central

    Liu, Qingyun; Via, Laura E.; Luo, Tao; Liang, Lili; Liu, Xin; Wu, Sufang; Shen, Qingyu; Wei, Wang; Ruan, Xianglin; Yuan, Xing; Zhang, Guolong; Barry, Clifton E.; Gao, Qian

    2015-01-01

    Genetic heterogeneity of Mycobacterium tuberculosis (MTB) within a patient has caused great concern as it might complicate antibiotic treatment and cause treatment failure. But the extent of genetic heterogeneity has not been described in detail nor has its association with heterogeneous treatment response. During treatment of a subject with MDR-TB, serial computed tomography (CT) scans showed this subject had six anatomically discrete lesions and they responded to treatment with disparate kinetics, suggesting heterogeneous MTB population may exist. To investigate this heterogeneity, we applied deep whole genome sequencing of serial sputum isolates and discovered that the MTB population within this patient contained three dominant sub-clones differing by 10 ~ 14 single nucleotide polymorphisms (SNPs). Differential mutation patterns in known resistance alleles indicated these sub-clones had different drug-resistance patterns, which may explain the heterogeneous treatment responses between lesions. Our results showed clear evidence of branched microevolution of MTB in vivo, which led to a diverse bacterial community. These findings indicated that complex sub-populations of MTB might coexist within patient and contribute to lesions’ disparate responses to antibiotic treatment. PMID:26620446

  10. Costs associated with tuberculosis diagnosis and treatment in Yemen for patients and public health services.

    PubMed

    Othman, G Q; Ibrahim, M I M; Raja'a, Y A

    2012-04-01

    This study determined the costs associated with tuberculosis (TB) diagnosis and treatment for the public health services and patients in Sana'a, Yemen. Data were collected prospectively from 320 pulmonary and extrapulmonary TB patients (160 each) who were followed until completion of treatment. Direct medical and nonmedical costs and indirect costs were calculated. The proportionate cost to the patients for pulmonary TB and extrapulmonary TB was 76.1% arid 89.4% respectively of the total for treatment. The mean cost to patients for pulmonary and extrapulmonary TB treatment was US$ 108.4 and US$ 328.0 respectively. The mean cost per patient to the health services for pulmonary and extrapulmonary TB treatment was US$ 34.0 and US$ 38.8 respectively. For pulmonary and extrapulmonary TB, drug treatment represented 59.3% and 77.9% respectively of the total cost to the health services. The greatest proportionate cost to patients for pulmonary TB treatment was time away from work (67.5% of the total cost), and for extrapulmonary TB was laboratory and X-ray costs (55.5%) followed by transportation (28.6%).

  11. Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.

    PubMed

    Nahid, Payam; Dorman, Susan E; Alipanah, Narges; Barry, Pennan M; Brozek, Jan L; Cattamanchi, Adithya; Chaisson, Lelia H; Chaisson, Richard E; Daley, Charles L; Grzemska, Malgosia; Higashi, Julie M; Ho, Christine S; Hopewell, Philip C; Keshavjee, Salmaan A; Lienhardt, Christian; Menzies, Richard; Merrifield, Cynthia; Narita, Masahiro; O'Brien, Rick; Peloquin, Charles A; Raftery, Ann; Saukkonen, Jussi; Schaaf, H Simon; Sotgiu, Giovanni; Starke, Jeffrey R; Migliori, Giovanni Battista; Vernon, Andrew

    2016-10-01

    The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the

  12. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.

    PubMed

    Nahid, Payam; Dorman, Susan E; Alipanah, Narges; Barry, Pennan M; Brozek, Jan L; Cattamanchi, Adithya; Chaisson, Lelia H; Chaisson, Richard E; Daley, Charles L; Grzemska, Malgosia; Higashi, Julie M; Ho, Christine S; Hopewell, Philip C; Keshavjee, Salmaan A; Lienhardt, Christian; Menzies, Richard; Merrifield, Cynthia; Narita, Masahiro; O'Brien, Rick; Peloquin, Charles A; Raftery, Ann; Saukkonen, Jussi; Schaaf, H Simon; Sotgiu, Giovanni; Starke, Jeffrey R; Migliori, Giovanni Battista; Vernon, Andrew

    2016-10-01

    The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the

  13. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.

    PubMed

    Nahid, Payam; Dorman, Susan E; Alipanah, Narges; Barry, Pennan M; Brozek, Jan L; Cattamanchi, Adithya; Chaisson, Lelia H; Chaisson, Richard E; Daley, Charles L; Grzemska, Malgosia; Higashi, Julie M; Ho, Christine S; Hopewell, Philip C; Keshavjee, Salmaan A; Lienhardt, Christian; Menzies, Richard; Merrifield, Cynthia; Narita, Masahiro; O'Brien, Rick; Peloquin, Charles A; Raftery, Ann; Saukkonen, Jussi; Schaaf, H Simon; Sotgiu, Giovanni; Starke, Jeffrey R; Migliori, Giovanni Battista; Vernon, Andrew

    2016-10-01

    The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the

  14. Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.

    PubMed

    Nahid, Payam; Dorman, Susan E; Alipanah, Narges; Barry, Pennan M; Brozek, Jan L; Cattamanchi, Adithya; Chaisson, Lelia H; Chaisson, Richard E; Daley, Charles L; Grzemska, Malgosia; Higashi, Julie M; Ho, Christine S; Hopewell, Philip C; Keshavjee, Salmaan A; Lienhardt, Christian; Menzies, Richard; Merrifield, Cynthia; Narita, Masahiro; O'Brien, Rick; Peloquin, Charles A; Raftery, Ann; Saukkonen, Jussi; Schaaf, H Simon; Sotgiu, Giovanni; Starke, Jeffrey R; Migliori, Giovanni Battista; Vernon, Andrew

    2016-10-01

    The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the

  15. Methodology matters: what type of research is suitable for evaluating community treatment supporters for HIV and tuberculosis treatment?

    PubMed

    Maher, Dermot; Harries, Anthony D; Nachega, Jean B; Jaffar, Shabbar

    2012-03-01

    The choice of research method relevant to the evaluation of delivery of a health intervention is not always straightforward. We use the evaluation of HIV and tuberculosis community treatment supporters in promoting adherence to treatment in Africa as a case study to illustrate the pros and cons of operational research and randomised controlled trials. The choice of this intervention for the case study reflects the importance of maximising the benefits of unprecedented efforts to scale-up treatments of these two epidemics. International policy supporting the role of community treatment supporters in tuberculosis is largely based on the findings of operational research studies. This reflects the advantages that operational research is less costly than randomised controlled trials, provides more rapid answers to policy questions, enables standard evaluation of the intervention in 'real life' conditions in several diverse settings and has in-built potential to influence policy and practice, because the research is conducted within health programmes. Recent evidence on the role of community treatment supporters in HIV is largely based on randomised trials. This reflects the advantages that randomised trials compared to operational research are more rigorous and generate a more convincing result. Operational research and randomised trials may be viewed as providing complementary findings to inform new policies and practice aimed at improving programme performance and patient outcomes. However, in practice, insufficient funds are likely to be made available for randomised trials to answer all the current research questions on delivery of programme interventions. In deciding on the type of research to evaluate a particular health intervention, dialogue is necessary with policy-makers to weigh up explicitly the trade-offs between research rigour and other factors such as cost, speed of implementation of research and speed of policy uptake and of change in programme practice

  16. Xpert MTB/RIF: a New Pillar in Diagnosis of Extrapulmonary Tuberculosis?▿

    PubMed Central

    Vadwai, Viral; Boehme, Catharina; Nabeta, Pamela; Shetty, Anjali; Alland, David; Rodrigues, Camilla

    2011-01-01

    Approximately 10 to 15% of tuberculosis (TB) cases in India are estimated to have extrapulmonary disease, and due to a lack of diagnostic means, they often remain untreated. The early detection of Mycobacterium tuberculosis and multidrug resistance is a priority in TB diagnosis to improve the successful treatment rate of TB and reduce transmission. The Xpert MTB/RIF (Xpert) test, recently endorsed by the World Health Organization for the detection of pulmonary TB, was evaluated to test its utility in 547 patients with suspected extrapulmonary tuberculosis. Five hundred forty-seven extrapulmonary specimens were split and processed simultaneously for both culture (solid and liquid) and Xpert testing. For culture, the sensitivity was low, 53% (150/283 specimens). Xpert sensitivity and specificity results were assessed in comparison to a composite reference standard made up of smear and culture results and clinical, radiological, and histological findings. The sensitivity of the Xpert assay was 81% (228/283 specimens) (64% [89/138] for smear-negative cases and 96% [139/145] for smear-positive cases), with a specificity of 99.6%. The sensitivity was found to be high for the majority of specimen types (63 to 100%) except for cerebrospinal fluid, the sensitivity of which was 29% (2/7 specimens). The Xpert test correctly identified 98% of phenotypic rifampin (RIF)-resistant cases and 94% of phenotypic RIF-susceptible cases. Sequencing of the 6 discrepant samples resolved 3 of them, resulting in an increased specificity of 98%. In conclusion, the results of this study suggest that the Xpert test also shows good potential for the diagnosis of extrapulmonary TB and that its ease of use makes it applicable for countries where TB is endemic. PMID:21593262

  17. Is nonstructural bone graft useful in surgical treatment of lumbar spinal tuberculosis?

    PubMed Central

    Liu, Jia-Ming; Chen, Xuan-Yin; Zhou, Yang; Long, Xin-Hua; Chen, Wen-Zhao; Liu, Zhi-Li; Huang, Shan-Hu; Yao, Hao-Qun

    2016-01-01

    Abstract Surgical intervention is an important option for treating spinal tuberculosis. Previous studies have reported different surgical procedures and bone grafts for it. To our knowledge, few studies demonstrated the clinical results of using nonstructural autogenous bone graft in surgical treatment of spinal tuberculosis. The purpose of this study is to compare the clinical outcomes of surgical management lumbar spinal tuberculosis by one-stage posterior debridement with nonstructural autogenous bone grafting and instrumentation versus anterior debridement, strut bone grafting combined with posterior instrumentation. A total of 58 consecutive patients who underwent surgical treatment due to lumbar spinal tuberculosis from January 2011 to December 2013 were included. A total of 22 patients underwent one-stage posterior debridement, nonstructural autogenous bone grafting, and instrumentation (group A), and 36 patients received anterior debridement, strut bone grafting combined with posterior instrumentation (group B). The operative duration, total blood loss, perioperative transfusion, length of hospital stay, hospitalization cost, and complications were recorded. The bony fusion of the graft was assessed by computed tomography scans. American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate the neurological function of patients in the 2 groups. All the patients were followed up, with a mean follow-up duration of 21.6 ± 5.7 months in group A and 22.3 ± 6.2 months in group B (P = 0.47). The average operative duration was 257.5 ± 91.1 minutes in group A and 335.7 ± 91.0 minutes in group B (P = 0.002). The mean total blood loss was 769.6 ± 150.9 mL in group A and 1048.6 ± 556.9 mL in group B (P = 0.007). Also, significant differences were found between the 2 groups in perioperative transfusion volumes, length of hospital stay, and hospitalization cost (P < 0.05), which were less in group A

  18. Risk factors for nosocomial tuberculosis transmission among health care workers.

    PubMed

    Ito, Yutaka; Nagao, Miki; Iinuma, Yoshitsugu; Matsumura, Yasufumi; Yamamoto, Masaki; Takakura, Shunji; Igawa, Junko; Yamanaka, Hiroe; Hashimoto, Akiko; Hirai, Toyohiro; Niimi, Akio; Ichiyama, Satoshi; Mishima, Michiaki

    2016-05-01

    We conducted hospital-based contact investigations of 55 serial sputum smear-positive tuberculosis (TB) patients and 771 health care workers (HCWs) from 2006-2013. HCWs who made contact with TB patients in the absence of appropriate airborne precautions were evaluated using interferon gamma release assays to identify TB infection. Twenty-nine HCWs (3.8%) were newly diagnosed with TB infection. The 10 TB patients responsible for transmission had a duration of contact of >7 days by multivariate analysis. PMID:26777287

  19. Is repositioning of drugs a viable alternative in the treatment of tuberculosis?

    PubMed

    Palomino, Juan Carlos; Martin, Anandi

    2013-02-01

    Antimicrobial resistance is a serious problem because of the scarcity of new antibiotics effective against pathogens such as methicillin-resistant Staphylococcus aureus, β-lactamase-producing Gram-negative bacteria and multidrug-resistant Mycobacterium tuberculosis. Extensively drug resistance is particularly worrying in tuberculosis (TB), since the causative bacteria have become resistant to almost all available first- and second-line drugs and resistance is a threat to achieving control of the disease. Development of new drugs is a lengthy and costly endeavour. This is a particular problem for antibiotics, usage of which is likely to be of limited duration, and is even more true of antibiotics whose use is restricted to the treatment of a disease, such as TB, that is considered to be 'poverty related', and for which the return on the investment is seen as non-attractive. In spite of this, there is an emerging pipeline of new drugs under development that hopefully will bring new anti-TB drugs to the market in the near future. The strategy of drug repurposing, finding new uses for existing approved medicines, has seen unexpected success in other medical areas. More than one blockbuster drug has originated from this strategy. And in the field of TB, there have been several examples in recent years of this approach leading to the use of drugs for which there is undeniable evidence of efficacy in the treatment of the disease, the best example being the fluoroquinolones, which were not developed originally to treat TB. This article reviews some examples of repurposing of drugs in the treatment of TB, newer candidates for repurposing for which there is already preliminary evidence of activity and possible new options that merit further investigation.

  20. Incidence, Clinical Features and Impact on Anti-Tuberculosis Treatment of Anti-Tuberculosis Drug Induced Liver Injury (ATLI) in China

    PubMed Central

    Shang, Penghui; Xia, Yinyin; Liu, Feiying; Wang, Xiaomeng; Yuan, Yanli; Hu, Daiyu; Tu, Dehua; Chen, Yixin; Deng, Peiyuan; Cheng, Shiming; Zhou, Lin; Ma, Yu; Zhu, Lizhen; Gao, Weiwei; Wang, Hongyuan; Chen, Dafang; Yang, Li; He, Pingping; Wu, Shanshan; Tang, Shaowen; Lv, Xiaozhen; Shu, Zheng; Zhang, Yuan; Yang, Zhirong; Chen, Yan; Li, Na; Sun, Feng; Li, Xiaoting; He, Yingjian; Garner, Paul; Zhan, Siyan

    2011-01-01

    Background Anti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China. Methodology/Principal Findings In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%–3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69–15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI,1.23–3.60) risk of prolonged intensive treatment phase. Conclusions/Significance ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the

  1. Tuberculosis treatment and risk of stavudine substitution in first line antiretroviral therapy

    PubMed Central

    Westreich, Daniel J.; Sanne, Ian; Maskew, Mhairi; Malope-Kgokong, Babatyi; Conradie, Francesca; Majuba, Pappie; Funk, Michele Jonsson; Kaufman, Jay S.; Van Rie, Annelies; MacPhail, Patrick

    2009-01-01

    Background Treatment for tuberculosis (TB) is common among individuals receiving stavudine-containing highly active antiretroviral therapy (HAART), but the effect of TB treatment on stavudine toxicity has received little attention. We estimated the effect of TB treatment on risk of stavudine substitution among individuals receiving first-line HAART. Methods We evaluated a cohort of 7,066 patients who initiated HAART between April 2004 and March 2007 in Johannesburg, South Africa. Three exposure categories were considered: ongoing TB treatment at HAART initiation; concurrent initiation of TB treatment and HAART; incident TB treatment after HAART initiation. The outcome was single-drug stavudine substitution. Adjusted hazard ratios (aHRs) were estimated using marginal structural models to control for confounding, loss to follow-up, and competing risks. Results Individuals with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dose. For ongoing TB treatment, aHR was 3.18 (95% confidence interval [CI] 1.82-5.56) in the first two months of HAART, 2.51 (95% CI 1.77-3.54) in months 3-6, and 1.19 (95% CI 0.94-1.52) thereafter. For concurrent TB treatment, aHR was 6.60 (95% CI 3.03-14.37) in the first two months,1.88 (95% CI 0.87-4.09) in months 3-6, and 1.07 (95% CI 0.65-1.76) thereafter. There was no effect of incident TB on stavudine substitution risk. Conclusions Risk of stavudine substitution was increased among patients receiving TB treatment, especially soon after HAART initiation. In settings where alternative antiretroviral drugs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered. PMID:19385733

  2. The effectiveness of sputum pH analysis in the prediction of response to therapy in patients with pulmonary tuberculosis.

    PubMed

    Masuda, Makoto; Sato, Takashi; Sakamaki, Kentaro; Kudo, Makoto; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2015-01-01

    Purpose. The predictive factor of response to antituberculous therapy has not been fully elucidated. Airway acidity has been thought to be a potential indicator of the bactericidal activity. Therefore, we hypothesized that monitoring airway acidity by measuring sputum pH could predict response to therapy. Methods. A total of 47 patients having newly diagnosed, smear-positive, active pulmonary tuberculosis were enrolled between October 2011 and March 2014. Sputum samples were serially analyzed before and after treatment. Eligible patients who initiated a standard 6-month treatment were monitored for the length of time to sputum smear and culture conversion. Results. There were 39 patients who completed a 2-month intensive phase of isoniazid, rifampicin, pyrazinamide, and ethambutol therapy followed by a 4-month continuation phase of isoniazid and rifampicin. Although factors including age, cavitation, sputum grade, and use of an acid-suppressant were associated with initial low sputum pH in univariate analysis, multivariate analysis revealed that only age ≥61 years was a statistically important factor predicting low pH value (p = 0.005). Further outcome analysis showed that initial low sputum pH before treatment was the only factor significantly associated with shorter length of time to both sputum smear and culture conversion (p = 0.034 and 0.019, respectively) independent of the effects of age, sputum bacterial load, extent of lung lesion, and cavitation. Thus, initial low sputum pH indicated favorable response to anti-tuberculosis therapy. Conclusions. Measuring sputum pH is an easy and inexpensive way of predicting response to standard combination therapy in patients with pulmonary tuberculosis. PMID:26644982

  3. The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis

    PubMed Central

    Chung, Wou Young; Yoon, Dukyong; Lee, Keu Sung; Jung, Yun Jung; Kim, Young Sun; Sheen, Seung Soo; Park, Kwang Joo

    2016-01-01

    Abstract Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB. We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into “fast” and “slow” based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as “significant.” In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-γ levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%–93%), while specificity (92%–96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P

  4. Psychological distress and its effect on tuberculosis treatment outcomes in Ethiopia

    PubMed Central

    Tola, Habteyes Hailu; Shojaeizadeh, Davoud; Garmaroudi, Gholamreza; Tol, Azar; Yekaninejad, Mir Saeed; Ejeta, Luche Tadesse; Kebede, Abebaw; Karimi, Mehrdad; Kassa, Desta

    2015-01-01

    Background Psychological distress is the major comorbidity among tuberculosis (TB) patients. However, its magnitude, associated factors, and effect on treatment outcome have not been adequately studied in low-income countries. Objective This study aimed to determine the magnitude of psychological distress and its effect on treatment outcome among TB patients on treatment. Design A follow-up study was conducted in Addis Ababa, Ethiopia, from May to December 2014. Patients (N=330) diagnosed with all types of TB who had been on treatment for 1–2 months were enrolled consecutively from 15 randomly selected health centers and one TB specialized hospital. Data on sociodemographic variables and economic status were collected using a structured questionnaire. The presence of psychological distress was assessed at baseline (within 1–2 months after treatment initiation) and end point (6 months after treatment initiation) using the 10-item Kessler (K-10) scale. Alcohol use and tobacco smoking history were assessed using WHO Alcohol Use Disorder Identification Test and Australian Smoking Assessment Checklist, respectively. The current WHO TB treatment outcome definition was used to differentiate the end result of each patient at completion of the treatment. Results The overall psychological distress was 67.6% at 1–2 months and 48.5% at 6 months after treatment initiation. Multiple logistic regression analysis revealed that past TB treatment history [adjusted odds ratio (AOR): 3.76; 95% confidence interval (CI): 1.67–8.45], being on anti-TB and anti-HIV treatments (AOR: 5.35; 95% CI: 1.83–15.65), being unmarried (AOR: 4.29; 95% CI: 2.45–7.53), having alcohol use disorder (AOR: 2.95; 95% CI: 1.25–6.99), and having low economic status (AOR: 4.41; 95% CI: 2.44–7.97) were significantly associated with psychological distress at baseline. However, at 6 months after treatment initiation, only being a multidrug-resistant tuberculosis (MDR-TB) patient (AOR: 3.02; 95% CI

  5. Epidemiology of Tuberculosis in Immigrants in a Large City with Large-Scale Immigration (1991-2013)

    PubMed Central

    Orcau, Àngels; Millet, Joan-Pau; Ros, Miriam; Gil, Sonia; Caylà, Joan A.

    2016-01-01

    Background The increase in immigration in Barcelona between 2000 and 2008 forced a reorganization of the control of tuberculosis (TB). TB clinical units (TBCU) were created and community health workers (CHW) were gradually included. Objective To understand trends in the incidence of TB among immigrants, their main characteristics and treatment compliance during the period 1991–2013. Design We conducted a cross-sectional population-based study of cases detected among immigrants by the Tuberculosis Program in Barcelona, Spain. Sociodemographic, clinical characteristics and risk factors were described. The annual incidence was calculated for various periods and geographical areas of origin. In the linear trend analysis, a p-value of <0.05 was considered statistically significant. Results We detected 3,284 cases. Incidence decreased from 144.8/100,000 inhabitants in 1991 to 53.4/100,000 in 2013. Individuals born in Pakistan-India-Bangladesh had the highest average annual incidence (675/100,000). In all, 2,156 cases (65.7%) were male. 2,272 (69.2%) had pulmonary TB, of which 48.2% were smear-positive. 33% of the cases (1,093) lived in the inner city. Contact tracing (CT) coverage in smear-positive individuals rose from 56.8% in 1991–1999 to 81.4% in 2000–2013 (p<0.01); this value was less than 50% in people from Africa and Eastern European countries. The case fatality rate was 3.6% overall and 9.8% among those born in high-income countries (p<0.01). The highest rate of treatment default (12.8%) was observed among cases from the Maghreb. The rate of successful treatment increased from 69.9% in 1991–1999 to 87.5% in 2000–2013 (p<0.01). Conclusion The incidence of TB in immigrants is decreasing in Barcelona. Organizational actions, such as incorporating CHWs and TBCUs, have been decisive for the observed improvements. PMID:27749904

  6. Identification of multidrug resistance in previously treated tuberculosis patients: a mixed methods study in Cambodia

    PubMed Central

    Royce, S; Khann, S; Yadav, RP; Mao, ET; Cattamanchi, A; Sam, S; Handley, MA

    2014-01-01

    SUMMARY Setting Previously treated tuberculosis (TB) patients are a priority for drug susceptibility testing (DST) to identify cases with multidrug resistance (MDR). In Cambodia, a recent study found that only one-third of smear-positive previously treated patients had DST results. Objective To quantify the gaps in detecting MDR in previously treated TB patients in Cambodia, and describe health workers’ perspectives on barriers, facilitators and potential interventions. Design We analyzed case notifications in Cambodia (2004–2012) and conducted semi-structured interviews with key stakeholders Results The proportion of previously treated notifications varied significantly across provinces 2010–12, in the context of longer term trends of decreasing relapse and increasing “other” retreatment notifications. Correct classification of patients’ TB treatment history and ensuring specimens from previously-treated patients are collected and reach the laboratory could nearly double the number of detected MDR-TB cases. Identified barriers include patients’ reluctance to disclose and staff difficulty eliciting treatment history, partly due to availability of streptomycin only in hospitals. Facilitators include trained health workers, collection of sputum for DST even if previously treated patients are not taking streptomycin, streamlining sputum transportation and promptly reporting results. Conclusion Improved monitoring, supportive supervision, and correctly classifying previously treated patients are essential for improving detection of MDR-TB. PMID:25299861

  7. Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method

    PubMed Central

    White, Richard A.; Lu, Chunling; Rodriguez, Carly A.; Bayona, Jaime; Becerra, Mercedes C.; Burgos, Marcos; Centis, Rosella; Cohen, Theodore; Cox, Helen; D'Ambrosio, Lia; Danilovitz, Manfred; Falzon, Dennis; Gelmanova, Irina Y.; Gler, Maria T.; Grinsdale, Jennifer A.; Holtz, Timothy H.; Keshavjee, Salmaan; Leimane, Vaira; Menzies, Dick; Milstein, Meredith B.; Mishustin, Sergey P.; Pagano, Marcello; Quelapio, Maria I.; Shean, Karen; Shin, Sonya S.; Tolman, Arielle W.; van der Walt, Martha L.; Van Deun, Armand; Viiklepp, Piret

    2016-01-01

    Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection. We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference. Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34–0.42) for all patients and 0.33 (0.25–0.42) for HIV-co-infected patients. Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests. PMID:27587552

  8. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment.

    PubMed

    Pienaar, Elsje; Cilfone, Nicholas A; Lin, Philana Ling; Dartois, Véronique; Mattila, Joshua T; Butler, J Russell; Flynn, JoAnne L; Kirschner, Denise E; Linderman, Jennifer J

    2015-02-21

    While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials. The site of infection in TB is the granuloma, a collection of immune cells and bacteria that form in the lung, and new data suggest that penetration of drugs throughout granulomas is problematic. Here we integrate our computational model of granuloma formation and function with models for plasma pharmacokinetics, lung tissue pharmacokinetics and pharmacodynamics for two first line anti-TB antibiotics. The integrated model is calibrated to animal data. We make four predictions. First, antibiotics are frequently below effective concentrations inside granulomas, leading to bacterial growth between doses and contributing to the long treatment periods required for TB. Second, antibiotic concentration gradients form within granulomas, with lower concentrations toward their centers. Third, during antibiotic treatment, bacterial subpopulations are similar for INH and RIF treatment: mostly intracellular with extracellular bacteria located in areas non-permissive for replication (hypoxic areas), presenting a slowly increasing target population over time. Finally, we find that on an individual granuloma basis, pre-treatment infection severity (including bacterial burden, host cell activation and host cell death) is predictive of treatment outcome.

  9. [Multifocal tuberculosis in immunocompetent patients].

    PubMed

    Rezgui, Amel; Fredj, Fatma Ben; Mzabi, Anis; Karmani, Monia; Laouani, Chadia

    2016-01-01

    Multifocal tuberculosis is defined as the presence of lesions affecting at least two extrapulmonary sites, with or without pulmonary involvement. This retrospective study of 10 cases aims to investigate the clinical and evolutionary characteristics of multifocal tuberculosis. It included 41 cases with tuberculosis collected between 1999 and 2013. Ten patients had multifocal tuberculosis (24%): 9 women and 1 man, the average age was 50 years (30-68 years). Our patients were correctly BCG vaccinated. The evaluation of immunodepression was negative in all patients. 7 cases had lymph node tuberculosis, 3 cases digestive tuberculosis, 2 cases pericardial tuberculosis, 2 cases osteoarticular tuberculosis, 1 case brain tuberculosis, 2 cases urinary tuberculosis, 4 cases urogenital tuberculosis, 1 case adrenal tuberculosis, 1 case cutaneous and 1 case muscle tuberculosis. All patients received anti-tuberculosis treatment for a mean duration of 10 months, with good evolution. Multifocal tuberculosis is difficult to diagnose. It can affect immunocompetent patients but often has good prognosis. Anti-tuberculosis therapy must be initiated as soon as possible to avoid sequelae. PMID:27583077

  10. Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis.

    PubMed

    Chien, Jung-Yien; Chien, Shun-Tien; Chiu, Wei-Yih; Yu, Chong-Jen; Hsueh, Po-Ren

    2016-08-01

    It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were included in the study. Among the 81 patients with OFX-resistant MDR-TB, 50 (61.7%) were successfully treated and 31 (38.3%) had unfavorable outcomes, including treatment failure (n = 25; 30.9%), loss to follow-up (n = 2; 2.5%), and death (n = 4; 4.9%). Patients treated with MFX had a significantly higher rate of treatment success (77.3% versus 43.2%; odds ratio [OR] = 4.46, 95% confidence interval [CI] = 1.710 to 11.646, P = 0.002) than patients not treated with MFX, especially among those infected with MFX-susceptible isolates (40.7%) or isolates with low-level resistance to MFX (28.4%). Multivariate logistic regression analysis showed that treatment with MFX (adjusted odds ratio = 6.54, 95% CI = 1.44 to 29.59, P = 0.015) was the only independent factor associated with treatment success. Mutation at codon 94 in the gyrA gene was the most frequent mutation (68.0%) associated with high-level MFX resistance. Multivariate Cox proportional hazards regression analysis showed that treatment with MFX was also an independent factor associated with early culture conversion (hazard ratio = 3.12, 95% CI = 1.48 to 6.54, P = 0.003). Our results show that a significant proportion of OFX-resistant MDR-TB isolates were susceptible or had low-level resistance to MFX, indicating that patients with OFX-resistant MDR-TB benefit from treatment with MFX. PMID:27216062

  11. Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence.

    PubMed

    Vidal, Júlia Souza; Silva, Marcus Tolentino; Sanchez, Mauro Niskier

    2015-01-01

    Latent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy. PMID:26516958

  12. Impacts of 12-dose regimen for latent tuberculosis infection: Treatment completion rate and cost-effectiveness in Taiwan.

    PubMed

    Huang, Yi-Wen; Yang, Shun-Fa; Yeh, Yen-Po; Tsao, Thomas Chang-Yao; Tsao, Shih-Ming

    2016-08-01

    Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P <0.001). The cost of 3HP and 9H was US$261.24 and US$717.3, respectively. The cost-effectiveness ratio with isoniazid for 9 months was US$ 15392/avoided 1 case of tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment

  13. Emotional representation of tuberculosis with stigma, treatment delay, and medication adherence in Russia.

    PubMed

    Woith, Wendy M; Rappleyea, Megan L

    2016-05-01

    This descriptive cross-sectional study aimed to explore emotional representation and illness coherence, the understanding a person has about an illness which helps them make sense of the experience, in Russians with tuberculosis. In a secondary analysis of questionnaires from 105 Russians treated for pulmonary tuberculosis, social isolation and disease consequences were predictors of negative emotions related to tuberculosis and accounted for 49 percent of the variance. Participants who scored higher on illness coherence were less likely to experience negative emotions. Development of programs to help patients understand tuberculosis and to manage emotional responses and stigma is suggested.

  14. PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.

    PubMed

    Chen, Ray Y; Dodd, Lori E; Lee, Myungsun; Paripati, Praveen; Hammoud, Dima A; Mountz, James M; Jeon, Doosoo; Zia, Nadeem; Zahiri, Homeira; Coleman, M Teresa; Carroll, Matthew W; Lee, Jong Doo; Jeong, Yeon Joo; Herscovitch, Peter; Lahouar, Saher; Tartakovsky, Michael; Rosenthal, Alexander; Somaiyya, Sandeep; Lee, Soyoung; Goldfeder, Lisa C; Cai, Ying; Via, Laura E; Park, Seung-Kyu; Cho, Sang-Nae; Barry, Clifton E

    2014-12-01

    Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed. PMID:25473034

  15. Tuberculosis in native Israeli Arabs and Jews: trends and treatment outcomes, 1999-2011.

    PubMed

    Bishara, H; Goldblatt, D; Rorman, E; Mor, Z

    2015-11-01

    The incidence of tuberculosis (TB) in native ethnic minorities remains high in developed countries. Arabs, the major ethnic minority in Israel, comprise 21% of its population. This retrospective study compared TB incidence, demographic, clinical, laboratory, genotyping characteristics and treatment outcomes in all Israeli-born citizens diagnosed with TB between 1999 and 2011 by ethnicity, i.e. Israeli-born Arabs (IA) and Jews (IJ). A total of 831 Israeli-born TB patients were reported. Of those, there were 530 (64%) IJ and 301 (36%) IA, with an average annual TB rate of 1·1 and 1·6 cases/100 000 population, respectively, lower than the national average (7·0 cases/100 000 population). TB rates in IA and IJ declined and converged to 1 case/100 000 residents. IA TB patients were more likely to be older, have more pulmonary TB and have lower treatment success rates than IJ. Older age and HIV co-infection, but not ethnicity, were predictive of non-success in TB treatment. Ten mixed IA-IJ clades were detected by spoligotyping and three mixed IA-IJ clusters were identified by MIRU-VNTR typing. Only one IA-IJ couple recalled mutual contact. In conclusion, TB rate in IA was higher than in IJ, but declined and converged in both to 1 case/100 000. Treatment success was high in both groups, and was unrelated to ethnicity.

  16. Phytotherapeutic Information on Plants Used for the Treatment of Tuberculosis in Eastern Cape Province, South Africa

    PubMed Central

    Lawal, I. O.; Grierson, D. S.; Afolayan, A. J.

    2014-01-01

    The current rate of deforestation in Africa constitutes a serious danger to the future of medicinal plants on this continent. Conservation of these medicinal plants in the field and the scientific documentation of our knowledge about them are therefore crucial. An ethnobotanical survey of plants used for the treatment of tuberculosis (TB) was carried out in selected areas of the Eastern Cape, South Africa. These areas were Hala, Ncera, Sheshegu, and Gquamashe, all within the Nkonkobe Municipality. One hundred informants were interviewed. The survey included the identification of scientific and vernacular names of the plants used for treatment of TB as well as the methods of preparation and administration, the part used, dosage, and duration of treatment. The survey revealed 30 plants belonging to 21 families which are commonly used by traditional healers for the treatment of TB and associated diseases. Of these plants Clausena anisata, Haemanthus albiflos, and Artemisia afra were the most cited. The leaves were the most common part used in the medicinal preparations. Our findings are discussed in relation to the importance of the documentation of medicinal plants. PMID:24864158

  17. Factors associated with treatment default by tuberculosis patients in Fez, Morocco.

    PubMed

    Slama, K; Tachfouti, N; Obtel, M; Nejjari, C

    2013-08-01

    Interruption in tuberculosis (TB) treatment still remains the most important challenge for control of the disease. This study aimed to identify the determinants of TB treatment default in Fez, Morocco. A 1:2 pair-matched case-control study was carried out in the TB control units in Fez. Cases were defaulters to TB treatment and were matched by age and sex to non-defaulters (controls). Of the 320 patients (108 defaulters, 212 controls), 80.6% were male. The main reason for defaulting reported by patients was the sensation of being cured. Predictive factors for treatment default in the multivariate conditional logistic regression analysis, were: relapsed case (adjusted OR = 4.49; 95% Cl: 1.87-10.8), current smoking (aOR= 2.10; 95% Cl: 1.07-4.14), alcohol use (aOR = 2.92; 95% Cl: 1.04-8.19), being more than 30 minutes away from the health centre (aOR = 3.34; 95% Cl: 1.06-10.5) and perception of having received insufficient explanation about the disease (aOR = 2.87; 95% CI: 1.53-5.36). The rate of defaulting in Fez can be lowered through targeted and realistic measures.

  18. Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery.

    PubMed

    Datta, Meenal; Via, Laura E; Kamoun, Walid S; Liu, Chong; Chen, Wei; Seano, Giorgio; Weiner, Danielle M; Schimel, Daniel; England, Kathleen; Martin, John D; Gao, Xing; Xu, Lei; Barry, Clifton E; Jain, Rakesh K

    2015-02-10

    Tuberculosis (TB) causes almost 2 million deaths annually, and an increasing number of patients are resistant to existing therapies. Patients who have TB require lengthy chemotherapy, possibly because of poor penetration of antibiotics into granulomas where the bacilli reside. Granulomas are morphologically similar to solid cancerous tumors in that they contain hypoxic microenvironments and can be highly fibrotic. Here, we show that TB-infected rabbits have impaired small molecule distribution into these disease sites due to a functionally abnormal vasculature, with a low-molecular-weight tracer accumulating only in peripheral regions of granulomatous lesions. Granuloma-associated vessels are morphologically and spatially heterogeneous, with poor vessel pericyte coverage in both human and experimental rabbit TB granulomas. Moreover, we found enhanced VEGF expression in both species. In tumors, antiangiogenic, specifically anti-VEGF, treatments can "normalize" their vasculature, reducing hypoxia and creating a window of opportunity for concurrent chemotherapy; thus, we investigated vessel normalization in rabbit TB granulomas. Treatment of TB-infected rabbits with the anti-VEGF antibody bevacizumab significantly decreased the total number of vessels while normalizing those vessels that remained. As a result, hypoxic fractions of these granulomas were reduced and small molecule tracer delivery was increased. These findings demonstrate that bevacizumab treatment promotes vascular normalization, improves small molecule delivery, and decreases hypoxia in TB granulomas, thereby providing a potential avenue to improve delivery and efficacy of current treatment regimens.

  19. Social determinants of nonadherence to tuberculosis treatment in Buenos Aires, Argentina.

    PubMed

    Herrero, Maria Belen; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres

    2015-09-01

    This study aimed to identify the individual and environmental determinants of nonadherence to tuberculosis (TB) treatment in selected districts in the Buenos Aires Metropolitan Area, in Argentina. We conducted a cross-sectional study using a hierarchical model. Using primary and secondary data, logistic regression was performed to analyze two types of determinants. The likelihood of nonadherence to treatment was greatest among male patients. The following factors led to a greater likelihood of nonadherence to treatment: patients living in a home without running water; head of household without medical insurance; need to use more than one means of transport to reach the health center; place of residence in an area with a high proportion of households connected to the natural gas network; place of residence in an area where a large proportion of families fall below the minimum threshold of subsistence capacity; place of residence in an area where a high proportion of households do not have flushing toilets and basic sanitation. Our results show that social and economic factors - related to both individual and environmental characteristics - influence adherence to TB treatment. PMID:26578022

  20. Intermittent Versus Daily Pulmonary Tuberculosis Treatment Regimens: A Meta-Analysis

    PubMed Central

    Kasozi, Samuel; Clark, Justin; Doi, Suhail A. R.

    2015-01-01

    Background Several systematic reviews suggest that intermittent pulmonary tuberculosis (TB) chemotherapy is effective, but intensity (daily versus intermittent) and duration of rifampicin use (intensive phase only versus both phases) have not been distinguished. In addition, the various outcomes (success, failure, relapse, and default) have only selectively been evaluated. Methods We conducted a meta-analysis of proportions using all four outcomes as multi-category proportions to examine the effectiveness of WHO category 1 TB treatment regimens. Database searches of studies reporting treatment outcomes of HIV negative subjects were included and stratified by intensity of therapy and duration of rifampicin therapy. Using a bias-adjusted statistical model, we pooled proportions of the four treatment outcome categories using a method that handles multi-category proportions. Results A total of 27 studies comprising of 48 data sets with 10,624 participants were studied. Overall, treatment success was similar among patients treated with intermittent (I/I) (88%) (95% CI, 81–92) and daily (D/D) (90%) (95% CI, 84–95) regimens. Default was significantly less with I/I (0%) (95% CI, 0–2) compared to D/D regimens (5%) (95% CI, 1–9). Nevertheless, I/I relapse rates (7%) (95% CI, 3–11) were higher than D/D relapse rates (1%) (95% CI, 0–3). Conclusion Treatment regimens that are offered completely intermittently versus completely daily are associated with a trade-off between treatment relapse and treatment default. There is a possibility that I/I regimens can be improved by increasing treatment duration, and this needs to be urgently addressed by future studies. PMID:26056374

  1. A systematic review of delay in the diagnosis and treatment of tuberculosis

    PubMed Central

    Storla, Dag Gundersen; Yimer, Solomon; Bjune, Gunnar Aksel

    2008-01-01

    Background Early diagnosis and immediate initiation of treatment are essential for an effective tuberculosis (TB) control program. Delay in diagnosis is significant to both disease prognosis at the individual level and transmission within the community. Most transmissions occur between the onset of cough and initiation of treatment. Methods A systematic review of 58 studies addressing delay in diagnosis and treatment of TB was performed. We found different definitions of, for example, debut of symptoms, first appropriate health care provider, time to diagnosis, and start of treatment. Rather than excluding studies that failed to meet strict scientific criteria (like in a meta-analysis), we tried to extract the "solid findings" from all of them to arrive on a more global understanding of diagnostic delay in TB. Results The main factors associated with diagnostic delay included human immunodeficiency virus; coexistence of chronic cough and/or other lung diseases; negative sputum smear; extrapulmonary TB; rural residence; low access (geographical or sociopsychological barriers); initial visitation of a government low-level healthcare facility, private practitioner, or traditional healer; old age; poverty; female sex; alcoholism and substance abuse; history of immigration; low educational level; low awareness of TB; incomprehensive beliefs; self-treatment; and stigma. Conclusion The core problem in delay of diagnosis and treatment seemed to be a vicious cycle of repeated visits at the same healthcare level, resulting in nonspecific antibiotic treatment and failure to access specialized TB services. Once generation of a specific diagnosis was in reach, TB treatment was initiated within a reasonable period of time. PMID:18194573

  2. Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Treatment among Co-Infected Persons in South Africa, 2008–2010

    PubMed Central

    Webb Mazinyo, Ernesha; Kim, Lindsay; Masuku, Sikhethiwe; Lancaster, Joey L.; Odendaal, Ronel; Uys, Margot; Podewils, Laura Jean; Van der Walt, Martie L.

    2016-01-01

    Background Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. Methods A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008–31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence. Results Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). Conclusions The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment. PMID:27442440

  3. Factors Associated with Tuberculosis Treatment Default in an Endemic Area of the Brazilian Amazon: A Case Control-Study

    PubMed Central

    Garrido, Marlucia da Silva; Penna, Maria Lucia; Perez-Porcuna, Tomàs M.; de Souza, Alexandra Brito; Marreiro, Leni da Silva; Albuquerque, Bernardino Claudio; Martínez-Espinosa, Flor Ernestina; Bührer-Sékula, Samira

    2012-01-01

    Setting Treatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains. Objective This study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions. Design Observational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as ‘cases’ and those completing treatment as ‘controls’. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls. Results Treatment default was observed to be associated to previous default (aOR 3.20; p<0.001), HIV positivity (aOR 1.62; p<0.001), alcoholism (aOR 1.51; p<0.001), low education level (aOR 1.35; p<0.001) and other co-morbidities (aOR 1.31; p = 0.05). Older patients (aOR 0.98; p = 0.001) and DOT (aOR 0,72; p<0.01) were considered as protective factor for default. Conclusions Associated factors should be considered in addressing care and policy actions to tuberculosis control. Information on disease and treatment should be intensified and appropriate to the level of education of the population, in order to promote adherence to treatment and counter the spread of multidrug resistance to anti-TB drugs. PMID:22720052

  4. [Pharyngeal tuberculosis: Case report].

    PubMed

    Spini, Roxana Gabriela; Bordino, Lucas; Cohen, Daniela; Martins, Andrea; Ramírez, Zaida; González, Norma E

    2015-08-01

    Pharyngeal tuberculosis is a rare extrapulmonary manifestation. In Argentina, the number of cases of tuberculosis reported in children under 19 years in 2012 was 1752. Only 12.15% had extrapulmonary manifestation. A case of a 17 year old girl with pharyngeal tuberculosis is reported. The patient presented intermittent fever and swallowing pain for 6 months, without response to conventional antibiotic treatment. Chest X-ray showedbilateral micronodular infiltrate, so hospitalization was decided to study and treat. The sputum examination for acid-fast resistant bacilli was positive and treatment with four antituberculous drugs was started, with good evolution and disappearance of symptoms. Diagnostic confirmation with the isolation of Mycobacterium tuberculosis in sputum culture was obtained. The main symptoms of pharyngeal tuberculosis are sore throat and difficulty in swallowing of long evolution. It is important to consider tuberculosis as differential diagnosis in patients with chronic pharyngitis unresponsive to conventional treatment. PMID:26172025

  5. Treatment Outcomes in Tuberculosis Patients with Diabetes: A Polytomous Analysis Using Brazilian Surveillance System

    PubMed Central

    Reis-Santos, Bárbara; Gomes, Teresa; Locatelli, Rodrigo; de Oliveira, Elizabete R.; Sanchez, Mauro N.; Horta, Bernardo L.; Riley, Lee W.; Maciel, Ethel L.

    2014-01-01

    Background The impact of non-communicable diseases on tuberculosis incidence has received significant attention. It has been suggested that the risk of tuberculosis is higher among subjects with diabetes and these subjects also has poor TB treatment outcomes.This study was aimed at assessing the socio-demographic and clinical factors that may influence different outcome of TB in patients with DM (TB-DM) identified in the Brazilian national database from 2001 to 2011. Methods TB-DM cases reported in the Brazilian information system were identified and compared.Covariates associated with the outcomes of interest (cure, default, deaths, and development of TB MDR) were included in a hierarchical regression model. Results TB-DM cases increased from 380/100,000/year in 2001 to 6,150/100,000/year in 2011. Some of the main associations found are pointed. The odds of default was higher among those in the age group 20–39 years (OR = 2.07, 95%CI 1.32–3.24); alcoholics (OR = 2.17, 95%CI 1.86–2.54), and HIV/AIDS (OR = 2.16, 95%CI 1.70–2.74);positive monitoring smear (OR = 1.94, 95%CI 1.55–2.43); prior default (OR = 5.41, 95%CI 4.47–6.54), and unknown type of treatment (OR = 3.33, 95%CI 1.54–7.22). The odds of death was greater for subjects ≥60 years old (OR = 2.74, 95%CI 1.74–4.29); institutionalized in shelter (OR = 2.69, 95%CI 1.07–6.77); alcoholics (OR = 2.70, 95%CI 2.27–3.22); HIV/AIDS (OR = 2.87, 95%CI 2.13–3.86); pulmonary+extrapulmonary TB (OR = 2.49, 95%CI 1.79–3.46); with unknown type of treatment (OR = 14.12, 95%CI 7.04–28.32).Development of MDR TB was more related to relapse (OR = 9.60, 95%CI 6.07–15.14);previous default (OR = 17.13, 95%CI 9.58–30.63); and transfer of treatment center (OR = 7.87, 95%CI 4.74–13.07). Conclusions Older subjects and those with comorbidities and with a previous treatment of TB had poorest outcomes. TB control program in Brazil will need to expand

  6. Patients with Tuberculosis Have a Dysfunctional Circulating B-Cell Compartment, Which Normalizes following Successful Treatment

    PubMed Central

    del Nonno, Franca; Baiocchini, Andrea; Petrone, Linda; Vanini, Valentina; Smits, Hermelijn H.; Palmieri, Fabrizio; Goletti, Delia; Ottenhoff, Tom H. M.

    2016-01-01

    B-cells not only produce immunoglobulins and present antigens to T-cells, but also additional key roles in the immune system. Current knowledge on the role of B-cells in infections caused by intracellular bacteria is fragmentary and contradictory. We therefore analysed the phenotypical and functional properties of B-cells during infection and disease caused by Mycobacterium tuberculosis (Mtb), the bacillus causing tuberculosis (TB), and included individuals with latent TB infection (LTBI), active TB, individuals treated successfully for TB, and healthy controls. Patients with active or treated TB disease had an increased proportion of antibodies reactive with mycobacteria. Patients with active TB had reduced circulating B-cell frequencies, whereas only minor increases in B-cells were detected in the lungs of individuals deceased from TB. Both active TB patients and individuals with LTBI had increased relative fractions of B-cells with an atypical phenotype. Importantly, these B-cells displayed impaired proliferation, immunoglobulin- and cytokine- production. These defects disappeared upon successful treatment. Moreover, T-cell activity was strongest in individuals successfully treated for TB, compared to active TB patients and LTBI subjects, and was dependent on the presence of functionally competent B-cells as shown by cellular depletion experiments. Thus, our results reveal that general B-cell function is impaired during active TB and LTBI, and that this B-cell dysfunction compromises cellular host immunity during Mtb infection. These new insights may provide novel strategies for correcting Mtb infection-induced immune dysfunction towards restored protective immunity. PMID:27304615

  7. Tuberculosis Infection and Latent Tuberculosis

    PubMed Central

    2016-01-01

    Active tuberculosis (TB) has a greater burden of TB bacilli than latent TB and acts as an infection source for contacts. Latent tuberculosis infection (LTBI) is the state in which humans are infected with Mycobacterium tuberculosis without any clinical symptoms, radiological abnormality, or microbiological evidence. TB is transmissible by respiratory droplet nucleus of 1–5 µm in diameter, containing 1–10 TB bacilli. TB transmission is affected by the strength of the infectious source, infectiousness of TB bacilli, immunoresistance of the host, environmental stresses, and biosocial factors. Infection controls to reduce TB transmission consist of managerial activities, administrative control, engineering control, environmental control, and personal protective equipment provision. However, diagnosis and treatment for LTBI as a national TB control program is an important strategy on the precondition that active TB is not missed. Therefore, more concrete evidences for LTBI management based on clinical and public perspectives are needed. PMID:27790271

  8. Treatment Outcomes with Fluoroquinolone-Containing Regimens for Isoniazid-Resistant Pulmonary Tuberculosis

    PubMed Central

    Lee, Hyun; Jeong, Byeong-Ho; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Lee, Nam Yong

    2015-01-01

    Resistance to isoniazid (INH) is the most common form of drug resistance in pulmonary tuberculosis (TB). Although fluoroquinolones (FQs) are recommended to strengthen treatment regimens for INH-resistant pulmonary TB, few studies have evaluated the clinical efficacy of FQ-containing regimens in patients with INH-resistant pulmonary TB. A retrospective cohort study of 140 patients with INH-resistant pulmonary TB was performed between 2005 and 2012. We evaluated whether FQ-containing regimens yielded improved treatment outcomes for patients with INH-resistant pulmonary TB. Overall, favorable outcomes were achieved in 128 (91.4%) patients. Unfavorable outcomes occurred in 12 patients (8.6%), including 7 with treatment failure (5.0%) and 5 with relapse after initial treatment completion (3.6%). FQs, such as levofloxacin and moxifloxacin, were given to 75 (53.6%) patients. Favorable treatment outcomes were more frequent for patients who received FQs (97.3% [73/75 patients]) than for those who did not receive FQs (84.6% [55/65 patients]) (P = 0.007). Patients who did not receive FQs were more likely to develop treatment failure (9.2% [6/65 patients] versus 1.3% [1/75 patients]) (P = 0.049) than patients who received FQs. The adjusted proportion of unfavorable outcomes was significantly higher among patients who did not receive FQs (8.8%; 95% confidence interval [CI], 3.3 to 21.5%) than among those who did receive FQs (1.5%; 95% CI, 0.3 to 7.7%) (P = 0.037). These results suggest that the addition of FQs can improve treatment outcomes for patients with INH-resistant pulmonary TB. PMID:26525801

  9. The impact of pulmonary tuberculosis treatment on the prevalence of allergic rhinitis.

    PubMed

    Lin, Carren Teh Sui; Gopala, Krishnan; Manuel, Anura Michelle

    2013-08-01

    Atopy is a syndrome characterized by immediate hypersensitivity reactions to common environmental antigens. The "hygiene hypothesis" stipulates that childhood infections are associated with a lower risk of allergies. Not much has been published about the effects that the treatment of pulmonary tuberculosis (TB) has on allergies, specifically allergic rhinitis. We conducted a study to investigate the prevalence of allergic rhinitis in patients with pulmonary TB before and after treatment of their TB. Our initial study group was made up of 121 patients with confirmed pulmonary TB who were followed up by questionnaire. In addition to demographic data, they provided information about their personal and family history of atopy and their current status with regard to allergic rhinitis. After providing informed consent, all patients underwent skin-prick testing with Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis allergens before and after TB treatment. Stool samples were obtained to identify patients with worm infestation, and they were excluded from the study. In all, 94 patients completed treatment and follow-up, and their data were included in the final analysis. Of this group, 31 patients (33.0%) exhibited symptoms of allergic rhinitis prior to TB treatment, and 26 (27.7%) had a positive skin-prick test. Following treatment, only 12 patients (12.8%) reported allergic rhinitis symptoms (p = 0.004), but there was no significant reduction in the number of patients with a positive skin-prick test (n = 20 [21.3%]; p = 0.555). We conclude that the treatment of pulmonary TB results in significant relief of atopy, particularly allergic rhinitis symptoms.

  10. Tuberculosis situation among tribal population of Car Nicobar, India, 15 years after intensive tuberculosis control project and implementation of a national tuberculosis programme.

    PubMed Central

    Murhekar, M. V.; Kolappan, C.; Gopi, P. G.; Chakraborty, A. K.; Sehgal, S. C.

    2004-01-01

    OBJECTIVE: To assess the tuberculosis (TB) situation in the tribal community of Car Nicobar island 15 years after the national TB programme was implemented in this area after an intensive phase of TB control in 1986. METHODS: The entire population of Car Nicobar was enumerated through a house-to-house survey. Children aged <14 years were tuberculin tested and read for reaction sizes. Individuals aged >15 years were asked about the presence of chest symptoms (cough, chest pain, and unexplained fever for two weeks or longer and haemoptysis), and sputum samples were collected from patients with chest symptoms. Sputum samples were examined for presence of acid-fast bacilli. FINDINGS: Among the 4,543 children enumerated, 4,351 (95.8%) were tuberculin tested and read. Of the 981 children without bacille Calmette-Guerin scars, 161 (16.4%) were infected with TB. A total of 77 cases who were smear-positive for TB were detected from among 10,570 people aged >15 years; the observed smear-positive case prevalence was 728.5 per 100,000. The standardized prevalence of TB infection, annual risk of TB infection, and prevalence of cases smear-positive for TB were 17.0%, 2.5%, and 735.3 per 100,000, respectively. CONCLUSION: The prevalence of TB infection and smear-positive cases of TB increased significantly between 1986 and 2002. Such escalation took place despite the implementation of the national TB programme on this island, which was preceded by a set of special anti-TB measures that resulted in sputum conversion in a substantially large proportion of the smear-positive cases prevalent in the community. The most likely reason for the increase seems to be the absence of a district TB programme with enough efficiency to sustain the gains made from the one-time initial phase of special anti-TB measures. High risk of transmission of TB infection currently observed on this island calls for a drastic and sustained improvement in TB control measures. PMID:15640919

  11. Diagnosis and Treatment of Childhood Pulmonary Tuberculosis: A Cross-Sectional Study of Practices among Paediatricians in Private Sector, Mumbai

    PubMed Central

    Tauro, Carolyn Kavita; Gawde, Nilesh Chandrakant

    2015-01-01

    Majority of children with tuberculosis are treated in private sector in India with no available data on management practices. The study assessed diagnostic and treatment practices related to childhood pulmonary tuberculosis among paediatricians in Mumbai's private sector in comparison with International Standards for Tuberculosis Care (ISTC) 2009. In this cross-sectional study, 64 paediatricians from private sector filled self-administered questionnaires. Cough was reported as a symptom of childhood TB by 77.8% of respondents. 38.1% request sputum smear or culture for diagnosis and fewer (32.8%) use it for patients positive on chest radiographs and 32.8% induce sputum for those unable to produce it. Sputum negative TB suspect is always tested with X-ray or tuberculin skin test. 61.4% prescribe regimen as recommended in ISTC and all monitor progress to treatment clinically. Drug-resistance at beginning of treatment is suspected for child in contact with a drug-resistant patient (67.7%) and with prior history of antitubercular treatment (12.9%). About half of them (48%) request drug-resistance test for rifampicin in case of nonresponse after two to three months of therapy and regimen prescribed by 41.7% for multidrug-resistant TB was as per ISTC. The study highlights inappropriate diagnostic and treatment practices for managing childhood pulmonary TB among paediatricians in private sector. PMID:26379705

  12. Tuberculosis notifications, characteristics and treatment outcomes: urban vs. rural Solomon Islands, 2000–2011

    PubMed Central

    Hill, P. C.; Bissell, K.; Harries, A. D.; Viney, K.; Gounder, S.

    2014-01-01

    Setting: All provincial tuberculosis (TB) management units in the Solomon Islands. Objective: To compare TB notifications, characteristics and treatment outcomes in urban vs. rural areas. Design: A retrospective descriptive cohort study involving record review and data extraction from provincial TB and laboratory registers and treatment charts from 2000 to 2011. Results: Of 4137 TB cases notified, 1364 (33%) were from urban and 3227 (67%) from rural areas. Notification rates per year of study were consistently higher in urban areas (104–150 per 100 000 population) than in rural areas (49–70/100 000). Cases in rural areas were more likely to have smear-negative pulmonary TB and less likely to have extra-pulmonary TB (P < 0.001). TB cases in rural areas were more likely to die from TB than those from urban areas (3.2% vs. 5.9%). In contrast, TB cases in rural areas were less likely to default (2.8% vs. 1.8%). Conclusion: TB notification rates were much higher in urban than in rural areas in the Solomon Islands. Rural patients are more likely to die from the disease but are slightly less likely to default. Further research is required to explore the possibility of under-reporting in rural areas and to improve treatment outcomes. PMID:26477283

  13. An ontology for factors affecting tuberculosis treatment adherence behavior in sub-Saharan Africa

    PubMed Central

    Ogundele, Olukunle Ayodeji; Moodley, Deshendran; Pillay, Anban W; Seebregts, Christopher J

    2016-01-01

    Purpose Adherence behavior is a complex phenomenon influenced by diverse personal, cultural, and socioeconomic factors that may vary between communities in different regions. Understanding the factors that influence adherence behavior is essential in predicting which individuals and communities are at risk of nonadherence. This is necessary for supporting resource allocation and intervention planning in disease control programs. Currently, there is no known concrete and unambiguous computational representation of factors that influence tuberculosis (TB) treatment adherence behavior that is useful for prediction. This study developed a computer-based conceptual model for capturing and structuring knowledge about the factors that influence TB treatment adherence behavior in sub-Saharan Africa (SSA). Methods An extensive review of existing categorization systems in the literature was used to develop a conceptual model that captured scientific knowledge about TB adherence behavior in SSA. The model was formalized as an ontology using the web ontology language. The ontology was then evaluated for its comprehensiveness and applicability in building predictive models. Conclusion The outcome of the study is a novel ontology-based approach for curating and structuring scientific knowledge of adherence behavior in patients with TB in SSA. The ontology takes an evidence-based approach by explicitly linking factors to published clinical studies. Factors are structured around five dimensions: factor type, type of effect, regional variation, cross-dependencies between factors, and treatment phase. The ontology is flexible and extendable and provides new insights into the nature of and interrelationship between factors that influence TB adherence. PMID:27175067

  14. Evaluation of tuberculosis public health surveillance, Al-Madinah province, Kingdom of Saudi Arabia, 2012.

    PubMed

    Alkhalawi, Mohammed J; McNabb, Scott J N; Assiri, Abdullah M; Memish, Ziad A

    2016-03-01

    The objective of the study is to evaluate the quality of the data, the sensitivity of the surveillance, and the completeness of identification and investigation of tuberculosis (TB) patient's contacts. The study covered the TB surveillance program in Al-Madinah province in 2011. First, we reviewed all the notifications, treatment cards, and register books, as well as monthly and quarterly reports, for completeness and accuracy of data. Then, we searched for the missed cases that were not reported. Finally, we reviewed all the patients' household contacts' reports to assess the degree of completion of identification and investigation. There were 444 cases detected during the study period; only 200 cases were reported. The sensitivity of the TB surveillance system was 45%. Among the 200 reported cases, the results revealed high completeness rates for demographic and disease data and low completeness rates for the test result fields. The contact identification and investigation showed that 34.4% of smear-positive cases' contacts were not identified. Only 67% of identified contacts were investigated. The review of hospital records and lab registers showed that 244 cases were not reported. In conclusion, the TB surveillance system has several areas that need improvement.

  15. Tuberculosis in Somalia.

    PubMed

    Turpie, I D

    2008-05-01

    This is a description of a tuberculosis treatment programme in a country at war where security and the absence of order pose problems to health care delivery. It is also a description of an epidemic of tuberculosis where treatment and diagnosis are difficult and the methods used have changed little in many years. More international pressure is needed.

  16. Acceleration of Tuberculosis Treatment by Adjunctive Therapy with Verapamil as an Efflux Inhibitor

    PubMed Central

    Gupta, Shashank; Tyagi, Sandeep; Almeida, Deepak V.; Maiga, Mariama C.; Ammerman, Nicole C.

    2013-01-01

    Rationale: A major priority in tuberculosis (TB) is to reduce effective treatment times and emergence of resistance. Recent studies in macrophages and zebrafish show that inhibition of mycobacterial efflux pumps with verapamil reduces the bacterial drug tolerance and may enhance drug efficacy. Objectives: Using mice, a mammalian model known to predict human treatment responses, and selecting conservative human bioequivalent doses, we tested verapamil as an adjunctive drug together with standard TB chemotherapy. As verapamil is a substrate for CYP3A4, which is induced by rifampin, we evaluated the pharmacokinetic/pharmacodynamic relationships of verapamil and rifampin coadministration in mice. Methods: Using doses that achieve human bioequivalent levels matched to those of standard verapamil, but lower than those of extended release verapamil, we evaluated the activity of verapamil added to standard chemotherapy in both C3HeB/FeJ (which produce necrotic granulomas) and the wild-type background C3H/HeJ mouse strains. Relapse rates were assessed after 16, 20, and 24 weeks of treatment in mice. Measurements and Main Results: We determined that a dose adjustment of verapamil by 1.5-fold is required to compensate for concurrent use of rifampin during TB treatment. We found that standard TB chemotherapy plus verapamil accelerates bacterial clearance in C3HeB/FeJ mice with near sterilization, and significantly lowers relapse rates in just 4 months of treatment when compared with mice receiving standard therapy alone. Conclusions: These data demonstrate treatment shortening by verapamil adjunctive therapy in mice, and strongly support further study of verapamil and other efflux pump inhibitors in human TB. PMID:23805786

  17. A Step toward Tuberculosis Elimination in a Low-Incidence Country: Successful Diagnosis and Treatment of Latent Tuberculosis Infection in a Refugee Clinic.

    PubMed

    Rennert-May, Elissa; Hansen, Elisabeth; Zadeh, Toktam; Krinke, Valerie; Houston, Stan; Cooper, Ryan

    2016-01-01

    Objectives. Approximately 65 percent of tuberculosis (TB) cases in Canada each year occur from reactivation in foreign-born individuals. Refugees are at high risk after immigration. Routine screening of this population for latent TB infection (LTBI) is generally considered infeasible. We evaluated the outcome of LTBI screening and treatment amongst refugees. Methods. Government-sponsored refugees in Edmonton are seen at the New Canadians' Clinic and screened for TB and LTBI. We reviewed records of patients between 2009 and 2011. Completeness of initial assessment, diagnosis of latent infection, and completion of LTBI treatment were evaluated. Treatment for LTBI was offered when patients had a positive Tuberculin Skin Test (TST) and risk factors for progression to TB. An Interferon-Gamma Release Assay (IGRA) was performed on all other TST positives; treatment is only offered if it was positive. Results. 949 refugees were evaluated. 746 TSTs were read, with 265 positive individuals. IGRA testing was performed in 203 TST positive individuals without other TB risk factors; 110 were positive. LTBI treatment was offered to 147 of 151 eligible patients, 141 accepted, and 103 completed a treatment course. Conclusion. We observed high proportions of patient retention, completion of investigations, and treatment. This care model promises to be a component of effective TB prevention in this high-risk population. PMID:27445565

  18. A Step toward Tuberculosis Elimination in a Low-Incidence Country: Successful Diagnosis and Treatment of Latent Tuberculosis Infection in a Refugee Clinic

    PubMed Central

    Rennert-May, Elissa; Hansen, Elisabeth; Zadeh, Toktam; Krinke, Valerie; Houston, Stan; Cooper, Ryan

    2016-01-01

    Objectives. Approximately 65 percent of tuberculosis (TB) cases in Canada each year occur from reactivation in foreign-born individuals. Refugees are at high risk after immigration. Routine screening of this population for latent TB infection (LTBI) is generally considered infeasible. We evaluated the outcome of LTBI screening and treatment amongst refugees. Methods. Government-sponsored refugees in Edmonton are seen at the New Canadians' Clinic and screened for TB and LTBI. We reviewed records of patients between 2009 and 2011. Completeness of initial assessment, diagnosis of latent infection, and completion of LTBI treatment were evaluated. Treatment for LTBI was offered when patients had a positive Tuberculin Skin Test (TST) and risk factors for progression to TB. An Interferon-Gamma Release Assay (IGRA) was performed on all other TST positives; treatment is only offered if it was positive. Results. 949 refugees were evaluated. 746 TSTs were read, with 265 positive individuals. IGRA testing was performed in 203 TST positive individuals without other TB risk factors; 110 were positive. LTBI treatment was offered to 147 of 151 eligible patients, 141 accepted, and 103 completed a treatment course. Conclusion. We observed high proportions of patient retention, completion of investigations, and treatment. This care model promises to be a component of effective TB prevention in this high-risk population. PMID:27445565

  19. Design and construction of a DNA origami drug delivery system based on MPT64 antibody aptamer for tuberculosis treatment

    PubMed Central

    Ranjbar, Reza; Hafezi-Moghadam, Mohammad Sadegh

    2016-01-01

    Introduction With all of the developments on infectious diseases, tuberculosis (TB) remains a cause of death among people. One of the most promising assembly techniques in nano-technology is “scaffolded DNA origami” to design and construct a nano-scale drug delivery system. Because of the global health problems of tuberculosis, the development of potent new anti-tuberculosis drug delivery system without cross-resistance with known anti-mycobacterial agents is urgently needed. The aim of this study was to design a nano-scale drug delivery system for TB treatment using the DNA origami method Methods In this study, we presented an experimental research on a DNA drug delivery system for treating Tuberculosis. TEM images were visualized with an FEI Tecnai T12 BioTWIN at 120 kV. The model was designed by caDNAno software and computational prediction of the 3D solution shape and its flexibility was calculated with a CanDo server. Results Synthesizing the product was imaged using transmission electron microscopy after negative-staining by uranyl formate. Conclusion We constructed a multilayer 3D DNA nanostructure system by designing square lattice geometry with the scaffolded-DNA-origami method. With changes in the lock and key sequences, we recommend that this system be used for other infectious diseases to target the pathogenic bacteria. PMID:27053991

  20. Surgical treatment of selected patients with multilevel contiguous thoracolumbar spinal tuberculosis by only posterior instrumentation without any bone fusion.

    PubMed

    Shen, Xiongjie; Huang, Xiangwang; Xiao, Sheng; Liu, Hongzhe; Zhang, Yi; Xiang, Tiecheng; Wang, Guoping; Sheng, Bin; Huang, Shu; Liu, Xiangyang

    2015-01-01

    The retrospective clinical study is to determine the feasibility and efficacy of surgical management of multilevel contiguous thoracolumbar spinal tuberculosis (MCTLST) by only posterior instrumentation without posterior or anterior bone fusion and without anterior fixation in the study of eleven selected cases. Eleven selected cases with MCTLST were treated with combined posterior instrumentation and debridement and/or decompression without any bone fusion. The mean follow-up was 33.1 months (range 20-48 months). The kyphosis angle ranged from 9.2 to 40.4° before operation, 27.8° in average. The American Spinal Injury Association (ASIA) score system was used to evaluate the neurological deficits and erythrocytesedimentationrate (ESR) used to judge the activity of tuberculosis, which were collected at certain time. Spinal tuberculosis (STB) was completely cured in all eleven patients. There was no recurrent tuberculosis infection. The postoperative kyphosis angle was 7.1° to 12.5°, 9.6° in average and there was no significant loss of the correction at the final follow-up. Solid fusion was achieved in all cases. Neurological condition in all patients was improved after surgery. In conclusions, combined posterior instrumentation and debridement and/or decompression without any bone fusion can be a feasible and effective method in treatment of patients with MCTLST. However, the strict selection of patients was the critical of the surgery success.

  1. Surgical treatment of selected patients with multilevel contiguous thoracolumbar spinal tuberculosis by only posterior instrumentation without any bone fusion

    PubMed Central

    Shen, Xiongjie; Huang, Xiangwang; Xiao, Sheng; Liu, Hongzhe; Zhang, Yi; Xiang, Tiecheng; Wang, Guoping; Sheng, Bin; Huang, Shu; Liu, Xiangyang

    2015-01-01

    The retrospective clinical study is to determine the feasibility and efficacy of surgical management of multilevel contiguous thoracolumbar spinal tuberculosis (MCTLST) by only posterior instrumentation without posterior or anterior bone fusion and without anterior fixation in the study of eleven selected cases. Eleven selected cases with MCTLST were treated with combined posterior instrumentation and debridement and/or decompression without any bone fusion. The mean follow-up was 33.1 months (range 20-48 months). The kyphosis angle ranged from 9.2 to 40.4° before operation, 27.8° in average. The American Spinal Injury Association (ASIA) score system was used to evaluate the neurological deficits and erythrocytesedimentationrate (ESR) used to judge the activity of tuberculosis, which were collected at certain time. Spinal tuberculosis (STB) was completely cured in all eleven patients. There was no recurrent tuberculosis infection. The postoperative kyphosis angle was 7.1° to 12.5°, 9.6° in average and there was no significant loss of the correction at the final follow-up. Solid fusion was achieved in all cases. Neurological condition in all patients was improved after surgery. In conclusions, combined posterior instrumentation and debridement and/or decompression without any bone fusion can be a feasible and effective method in treatment of patients with MCTLST. However, the strict selection of patients was the critical of the surgery success. PMID:26770474

  2. The Influence of Mining and Human Immunodeficiency Virus Infection Among Patients Admitted for Retreatment of Tuberculosis in Northern Tanzania.

    PubMed

    Mpagama, Stellah G; Lekule, Isaack A; Mbuya, Alexander W; Kisonga, Riziki M; Heysell, Scott K

    2015-08-01

    In tuberculosis (TB)-prevalent settings, patients admitted for retreatment of TB may account for a high burden of poor treatment outcome. We performed a retrospective cohort study to characterize retreatment patients and outcomes at a TB referral hospital in northern Tanzania. From 2009 to 2013, 185 patients began a retreatment regimen, the majority for relapse after prior treatment completion. Men accounted for an unexpected majority (88%), 36 (20%) were human immunodeficiency virus (HIV) infected and for 45 (24%) mining was their primary occupation. A poor outcome (death, default, or persistent smear positivity after 7 months of treatment) was found in 37 (23%). HIV infection was the only significant predictor of poor outcome (adjusted odds ratio [aOR] = 2.50, 95% confidence interval [CI] = 1.07-5.83, P = 0.034). Interventions to minimize need for retreatment or improve retreatment success may be regionally specific. In our setting, community-based diagnosis and management among at-risk subpopulations such as miners and those HIV infected appear of highest yield.

  3. The Influence of Mining and Human Immunodeficiency Virus Infection among Patients Admitted for Retreatment of Tuberculosis in Northern Tanzania

    PubMed Central

    Mpagama, Stellah G.; Lekule, Isaack A.; Mbuya, Alexander W.; Kisonga, Riziki M.; Heysell, Scott K.

    2015-01-01

    In tuberculosis (TB)–prevalent settings, patients admitted for retreatment of TB may account for a high burden of poor treatment outcome. We performed a retrospective cohort study to characterize retreatment patients and outcomes at a TB referral hospital in northern Tanzania. From 2009 to 2013, 185 patients began a retreatment regimen, the majority for relapse after prior treatment completion. Men accounted for an unexpected majority (88%), 36 (20%) were human immunodeficiency virus (HIV) infected and for 45 (24%) mining was their primary occupation. A poor outcome (death, default, or persistent smear positivity after 7 months of treatment) was found in 37 (23%). HIV infection was the only significant predictor of poor outcome (adjusted odds ratio [aOR] = 2.50, 95% confidence interval [CI] = 1.07–5.83, P = 0.034). Interventions to minimize need for retreatment or improve retreatment success may be regionally specific. In our setting, community-based diagnosis and management among at-risk subpopulations such as miners and those HIV infected appear of highest yield. PMID:26013368

  4. Peritoneal tuberculosis.

    PubMed

    Guirat, A; Koubaa, M; Mzali, R; Abid, B; Ellouz, S; Affes, N; Ben Jemaa, M; Frikha, F; Ben Amar, M; Beyrouti, M I

    2011-01-01

    The peritoneum is one of the locations outside the most common pulmonary tuberculosis. Peritoneal tuberculosis poses a public health problem in endemic regions of the world. The phenomenon of migration, the increased use of immunosuppressive therapy and the epidemic of AIDS have contributed to a resurgence of this disease in regions where it was previously controlled. The aim of this review is to expose the clinical, biologic end radiologic futures of the peritoneal tuberculosis and to present the methods of diagnosis and treatment. The diagnosis of this disease is difficult and still remains a challenge because of its insidious nature, the variability of presentation and limitations of available diagnostic tests. The disease usually presents a picture of lymphocytic exudative ascites. There are many complementary tests with variable sensitivities and specificities to confirm the diagnosis of peritoneal tuberculosis. Isolation of mycobacteria by culture of ascitic fluid or histological examination of peritoneal biopsy ideally performed by laparoscopy remains the investigation of choice. The role of PCR, ascitic adenosine deaminase, interferon gamma and the radiometric BACTEC system can improve the diagnostic yield. An antituberculous treatment with group 1 of the WHO for 6 months is sufficient in most cases.

  5. Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India.

    PubMed

    Singhal, Ritu; Reynolds, Paul R; Marola, Jamie L; Epperson, L Elaine; Arora, Jyoti; Sarin, Rohit; Myneedu, Vithal Prasad; Strong, Michael; Salfinger, Max

    2016-09-01

    Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in the gyrA and gyrB genes of Mycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in the gyrA and gyrB genes of acid-fast bacillus (AFB) smear-positive sediments or of M. tuberculosis isolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of the gyrA and gyrB genes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in the gyrA genes of 25 strains, while no mutations were observed in the gyrB genes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. The gyrA mutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis. PMID:27335153

  6. Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011

    PubMed Central

    Tran, Huong Thi Giang; Bui, Quyen Thi Tu

    2016-01-01

    Introduction Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Methods Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. Results A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. Conclusion This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance. PMID:27508089

  7. Factors Affecting Mortality and Treatment Completion of Tuberculosis Patients in Isfahan Province from 2006 to 2011

    PubMed Central

    Shahrezaei, Marzieh; Maracy, Mohammad Reza; Farid, Fariba

    2015-01-01

    Background: Regarding cases of infectious diseases tuberculosis (TB) is the most important cause of death and according to the DALY criteria, this disease has the seventh position in global disease ranking. In this study, we aim to determine the risk factors, which have a significant effect on the treatment completion and mortality of TB patients. Methods: This study is a retrospective cohort study. The sample is made up of registered TB patients in the Isfahan Province from 2006 to 2011. Information of the patients was collected from their files in health centers in the Isfahan Province. Variables such as age, sex, weight, nationality, residence, type of TB, imprisonment, human immunodeficiency virus, TB case were measured. Descriptive statistics (including frequency, percentage, mean and standard deviation) and statistical analysis (including Cox proportional hazard model) were used. Results: The result showed that imprisonment (hazard ratio [HR] = 4.76, P = 0.019), age (HR = 4.44, P = 0.001) and the TB case (HR = 2.73, P = 0.037) of pulmonary TB had significant impacts on mortality of the patients, also in the case of treatment completion, the TB case (HR = 0.34, P < 0.001) proved to have a significant impact on completion of the treatment. Type of extra-pulmonary TB in extra-pulmonary TB patients also had an effect on treatment completion. Conclusions: We can conclude that factors such as age, imprisonment, TB case and type of extra-pulmonary TB are effective on the treatment completion and mortality of the patients. It may be useful for policy makers to make more control of high-risk patients. PMID:26445638

  8. Delays in presenting for tuberculosis treatment associated with fear of learning one is HIV-positive.

    PubMed

    Møller, Valerie; Erstad, Ida; Cramm, Jane M; Nieboer, Anna P; Finkenflügel, Harry; Radloff, Sarah; Ndoro, Tinashe; Kwizera, Stella A

    2011-04-01

    A cornerstone of tuberculosis (TB) control is early diagnosis and treatment. The first hurdle that prospective TB patients must overcome is to present at a public health clinic for treatment. The Global Plan to Stop TB addresses the new challenges of the intersecting epidemics of TB and HIV, and it aims to cut the transmission chain by achieving early and effective treatment of all people with TB infection. This goal may be more difficult to achieve in practice. Findings from a representative community survey conducted in an area of high HIV prevalence in the Eastern Cape Province of South Africa suggest that patients must conquer fear of knowing their HIV status in order to present for TB diagnosis and treatment. A total of 1 020 adults residing in a low-income suburb of Grahamstown, Makana Municipality, participated in a questionnaire survey that probed attitudes and opinions about TB and HIV/AIDS-related issues. The respondents were presented with eight factors previously cited in the literature as causing delays in presenting for TB treatment at a public health clinic. The single largest proportion of respondents attributed delay to a fear of discovering that one is HIV-positive. While the vast majority of the respondents agreed that knowing one's HIV status is a civic responsibility ('the right thing to do'), half indicated that the lack of privacy during voluntary counselling and testing for HIV at a public health clinic acts as a disincentive. The evidence suggests that a fear of knowing one's HIV status is a deep-seated anxiety that is often not openly acknowledged, and that it is intertwined with the stigma related to the 'new' TB associated with HIV and AIDS. It is crucial to allay this deep-seated fear in the general public so that South Africa's integrated HIV and TB services, designed to accelerate control of the twin epidemics, are successful.

  9. [The process of detection and treatment of cases of tuberculosis in a prison].

    PubMed

    Valença, Mariana Soares; Cezar-Vaz, Marta Regina; Brum, Clarice Brinck; Silva, Pedro Eduardo Almeida da

    2016-06-01

    This study seeks to analyze the process of detection and treatment of cases of tuberculosis (TB) in a prison in the south of Brazil. An active and passive search for TB was conducted to estimate the scale of TB in a prison with 764 inmates. In conjunction with the detection strategies and clinical follow-up of the 41 TB cases, participant observation and records in field diaries were performed, making it possible to analyze the scope and limitations of detection and treatment of cases of TB in prison. The development of search strategies is discussed along with the use of questionnaires to detect symptomatic cases, as well as the inadequacy of the clinical follow-up of TB cases, involvement of different workers and coordination between prison and health services. There is clear potential for the control of TB using an active search to induce the passive detection and screening for symptoms that - even skewed by the perceptions of inmates regarding symptoms of TB - enabled an increase in detection. The functional dynamics of prison life hamper the inclusion of health routines and can restrict actions to control TB and other diseases. In the process of control of TB in prisons, the feasibility of effective detection methods is as important as planning based on disease conditions, network services and workers involved. PMID:27383345

  10. The procurement landscape of pediatric tuberculosis treatment: a Global Drug Facility perspective.

    PubMed

    Scott, C; Gardiner, E; de Lucia, A

    2015-12-01

    Simple, quality-assured, child-friendly formulations of existing first-line anti-tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products.

  11. Ethnomedical Knowledge of Plants Used for the Treatment of Tuberculosis in Johor, Malaysia

    PubMed Central

    Sabran, Siti Fatimah; Mohamed, Maryati; Abu Bakar, Mohd Fadzelly

    2016-01-01

    This study documented ethnomedical knowledge of plants used for the treatment of tuberculosis (TB) and its related symptoms as practiced by the Jakun community of Kampung Peta, situated in Endau Rompin Johor National Park, Johor, Malaysia. Eight key informants were selected by snowball sampling technique and data about medicinal plants were collected by semistructured interviews, participatory observations, and focus group. Qualitative analysis was undertaken using thematic analysis. There were 23 species of plants (22 genera, 20 families) documented and herbarium specimens were deposited at the UTHM Herbarium. Dipterocarpus sublamellatus was recorded for the first time with ethnomedical uses while other species were previously reported. The qualitative approach employed in this study demonstrates the emic perspective in terms of perceptions on traditional herbal medicine, transfer of knowledge, significant taboos related with medicinal plants, and their conservation efforts. Local and biomedical terminology in treatment of TB showed substantial correspondence. The outcomes obtained in the study are worth being further investigated for conservation strategies and are worthy of verifying their ethnomedical claims scientifically. PMID:26881002

  12. The procurement landscape of pediatric tuberculosis treatment: a Global Drug Facility perspective.

    PubMed

    Scott, C; Gardiner, E; de Lucia, A

    2015-12-01

    Simple, quality-assured, child-friendly formulations of existing first-line anti-tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products. PMID:26564536

  13. Elucidating Emergence and Transmission of Multidrug-Resistant Tuberculosis in Treatment Experienced Patients by Whole Genome Sequencing

    PubMed Central

    Clark, Taane G.; Mallard, Kim; Coll, Francesc; Preston, Mark; Assefa, Samuel; Harris, David; Ogwang, Sam; Mumbowa, Francis; Kirenga, Bruce; O’Sullivan, Denise M.; Okwera, Alphonse; Eisenach, Kathleen D.; Joloba, Moses; Bentley, Stephen D.; Ellner, Jerrold J.; Parkhill, Julian; Jones-López, Edward C.; McNerney, Ruth

    2013-01-01

    Background Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings. We have used whole genome analysis to investigate M. tuberculosis strains isolated from treatment experienced patients with MDR-TB in Uganda over a period of four years. Methods and Findings We used high throughput genome sequencing technology to investigate small polymorphisms and large deletions in 51 Mycobacterium tuberculosis samples from 41 treatment-experienced TB patients attending a TB referral and treatment clinic in Kampala. This was a convenience sample representing 69% of MDR-TB cases identified over the four year period. Low polymorphism was observed in longitudinal samples from individual patients (2-15 SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three clusters comprising a total of 8 patients were found with almost identical genetic profiles, including mutations predictive for resistance to rifampicin and isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug susceptible disease were found to have acquired MDR strains, one of which shared its genotype with an isolate from another patient in the cohort. Conclusions Whole genome sequence analysis identified MDR-TB strains that were shared by more than one patient. The transmission of multidrug-resistant disease in this cohort of retreatment patients emphasises the importance of early detection and need for infection control. Consideration should be given to rapid testing for drug resistance in patients undergoing treatment to monitor the

  14. Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo

    PubMed Central

    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G.; Swaminathan, Soumya; Gumbo, Tawanda

    2016-01-01

    Background. No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. Methods. We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix. We then used the hollow fiber system (HFS) model of intracellular tuberculosis to identify optimal dose schedules and exposures of moxifloxacin and linezolid in combination. We mimicked pediatric half-lives and concentrations achieved by each drug. We sampled the peripheral compartment on days 0, 7, 14, 21, and 28 for Mtb quantification, and compared the slope of microbial kill of Mtb by these regimens to the standard regimen of isoniazid, rifampin, and pyrazinamide, based on exponential decline regression. Results. The full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 ± 0.66 for linezolid and 3.80 ± 1.34 hours for moxifloxacin. The kill rate constant was 0.060 ± 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 ± 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively. Conclusions. We identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children. PMID:27742639

  15. Tuberculosis preventive treatment in a single medical center and evaluation of the results

    PubMed Central

    ÇAKAR, BEYHAN; DEMIR, NALAN; KARNAK, DEMET; ÖZKARA, ŞEREF

    2014-01-01

    The aim of the present study was to evaluate the application of tuberculosis preventive treatment (TB-PT). Demographic data, indications and results for cases that received TB-PT at the Ankara Tuberculosis Control Dispensary No. 7 between 2008 and 2011 were retrospectively evaluated. The ‘Prevention with Drugs’ registry at the dispensary was used. A total of 463 cases received TB-PT, with the indications including close contact with an active TB case (44%), positive tuberculin skin test (TST) in a child <15 years-old (25%) and immunosuppressive therapy (31%). The immunosuppressed group (n=144) were administered steroids (10%) or tumor necrosis factor (TNF)-α inhibitors (90%). Indications of TST conversion and sequela lesions were not observed among the cases. The male/female ratio was 106/98 for cases with TB close contact, 61/54 for TST-positive cases and 85/59 for immunosuppressed cases. The mean ages of these groups were 9±5.7, 9.5±3.8 and 38±14.9 years, respectively. TB-PT was completed in 364 cases (78.6%), and the rate of discontinuation due to adverse effects was 1% for TB close contact and 2% for TST-positive cases, but 5% for immunosuppressed cases. While the percentage of TB close contact cases receiving TB-PT decreased during the four-year study period, the percentage of cases with immunosuppression (in particular patients using TNF-α inhibitors) increased. Among the studied cases, only two subjects developed active TB. The first case involved a 1.5-year-old female that had close contact exposure to TB from a parent, while the other case involved a 14-year-old TST-positive male (induration size,16 mm). In conclusion, patients receiving TB-PT should be monitored and/or followed-up carefully to control any side-effects from the treatment and development of active TB. PMID:25371747

  16. TB-SA antibody test for diagnosis and monitoring treatment outcome of sputum smear negative pulmonary tuberculosis patients.

    PubMed

    Li, Xinxu; Xu, Hancheng; Jiang, Shiwen; Jing, Kuanhe; Wang, Li; Liu, Xiaoqiu; Li, Weibin; Zhang, Hui; Wang, Lixia

    2011-09-01

    The objectives of this study were to evaluate the suitability of the TB-SA antibody test to diagnose tuberculosis in sputum smear negative (SS-) pulmonary tuberculosis (TB) patients and its applicability for monitoring treatment outcomes in these patients. This study was conducted in three counties/districts in Chongqing Municipality, Liaoning Province, China between June 2005 and June 2007. A total of 432 SS suspected pulmonary TB patients were recruited and their blood was collected prior to treatment, at the end of 1 month of treatment, 2 months of treatment and 6 months of treatment (E6MT). The serum samples were analyzed with a TB-SA antibody test kit. Of the 432 SS suspected pulmonary TB patients, serum samples were obtained at all time points in 316 patients and analyzed. The 316 patients were divided into three groups according to sputum smear and sputum culture results and the chest X-ray results before treatment and at E6MT. Ten point four percent were SS-/culture positive (C+), 73.1% were SS-/culture negative (C-) with X-rays abnormalities, and 16.5% were SS-/C- without X-rays abnormalities. The positive rates for TB-SA antibody in the three groups were 57.6, 44.6 and 44.2%, respectively, before treatment, and 18.2, 19.1 and 26.9%, respectively, at E6MT. There was a significant decrease in TB-SA antibody positivity with treatment for all 3 groups. The TB-SA antibody test may be a useful adjunct to diagnose tuberculosis in SS- pulmonary TB patients, and may be useful for monitoring treatment outcomes of SS- pulmonary TB patients. PMID:22299440

  17. Cost-comparison of different management policies for tuberculosis patients in Italy. AIPO TB Study Group.

    PubMed Central

    Migliori, G. B.; Ambrosetti, M.; Besozzi, G.; Farris, B.; Nutini, S.; Saini, L.; Casali, L.; Nardini, S.; Bugiani, M.; Neri, M.; Raviglione, M. C.

    1999-01-01

    Although in developing countries the treatment of tuberculosis (TB) cases is among the most cost-effective health interventions, few studies have evaluated the cost-effectiveness of TB control in low-prevalence countries. The aim of the present study was to carry out an economic analysis in Italy that takes into account both the perspective of the resource-allocating authority (i.e. the Ministry of Health) and the broader social perspective, including a cost description based on current outcomes applied to a representative sample of TB patients nationwide (admission and directly observed treatment (DOT) during the initial intensive phase of treatment); a cost-comparison analysis of two alternative programmes: current policy based on available data (scenario 1) and an hypothetical policy oriented more towards outpatient care (scenario 2) (both scenarios included the option of including or not including DOT outside hospital admission, and incentives) were compared in terms of cost per case treated successfully. Indirect costs (such as loss of productivity) were included in considerations of the broader social perspective. The study was designed as a prospective monitoring activity based on the supervised collection of forms from a representative sample of Italian TB units. Individual data were collected and analysed to obtain a complete economic profile of the patients enrolled and to evaluate the effectiveness of the intervention. A separate analysis was done for each scenario to determine the end-point at different levels of cure rate (50-90%). The mean length of treatment was 6.6 months (i.e. patients hospitalized during the intensive phase; length of stay was significantly higher in smear-positive patients and in human immunodeficiency virus (HIV) seropositive patients). Roughly six direct smear and culture examinations were performed during hospital admission and three during ambulatory treatment. The cost of a single bed day was US$186.90, whereas that of a

  18. Immunogenicity of mycobacterial vesicles in humans: identification of a new tuberculosis antibody biomarker.

    PubMed

    Ziegenbalg, Anke; Prados-Rosales, Rafael; Jenny-Avital, Elisabeth R; Kim, Ryung S; Casadevall, Arturo; Achkar, Jacqueline M

    2013-07-01

    Biomarkers for active tuberculosis (TB) are urgently needed. Mycobacteria produce membrane vesicles (MVs) that contain concentrated immune-modulatory factors that are released into the host. We evaluated the human immune responses to BCG and Mycobacterium tuberculosis MVs to characterize the antibody responses and identify potentially novel TB biomarkers. Serological responses to MVs were evaluated by ELISAs and immunoblots with sera from 16 sputum smear-positive, 12 smear-negative HIV uninfected pulmonary TB patients and 16 BCG vaccinated Tuberculin skin-test positive controls with and without latent tuberculosis infection. MVs from both BCG and M. tuberculosis induced similar responses and were strongly immunogenic in TB patients but not in controls. Several MV-associated antigens appear to induce robust antibody responses, in particular the arabinomanan portion of the cell wall glycolipid lipoarabinomannan. Three proteins at ≈ 36, 25, and 23 kDa were simultaneously recognized by sera from 16/16 smear-positive, 9/12 smear-negative TB patients and 0/16 controls. These results provide promise and encouragement that antibody responses to proteins enriched in MVs of pathogenic mycobacteria may constitute a novel TB biomarker signature that could have diagnostic information.

  19. Accessibility to tuberculosis control services and tuberculosis programme performance in southern Ethiopia

    PubMed Central

    Dangisso, Mesay Hailu; Datiko, Daniel Gemechu; Lindtjørn, Bernt

    2015-01-01

    Background Despite the expansion of health services and community-based interventions in Ethiopia, limited evidence exists about the distribution of and access to health facilities and their relationship with the performance of tuberculosis (TB) control programmes. We aim to assess the geographical distribution of and physical accessibility to TB control services and their relationship with TB case notification rates (CNRs) and treatment outcome in the Sidama Zone, southern Ethiopia. Design We carried out an ecological study to assess physical accessibility to TB control facilities and the association of physical accessibility with TB CNRs and treatment outcome. We collected smear-positive pulmonary TB (PTB) cases treated during 2003–2012 from unit TB registers and TB service data such as availability of basic supplies for TB control and geographic locations of health services. We used ArcGIS 10.2 to measure the distance from each enumeration location to the nearest TB control facilities. A linear regression analysis was employed to assess factors associated with TB CNRs and treatment outcome. Results Over a decade the health service coverage (the health facility–to-population ratio) increased by 36% and the accessibility to TB control facilities also improved. Thus, the mean distance from TB control services was 7.6 km in 2003 (ranging from 1.8 to 25.5 km) between kebeles (the smallest administrative units) and had decreased to 3.2 km in 2012 (ranging from 1.5 to 12.4 km). In multivariate linear regression, as distance from TB diagnostic facilities (b-estimate=−0.25, p<0.001) and altitude (b-estimate=−0.31, p<0.001) increased, the CNRs of TB decreased, whereas a higher population density was associated with increased TB CNRs. Similarly, distance to TB control facilities (b-estimate=−0.27, p<0.001) and altitude (b-estimate=−0.30, p<0.001) were inversely associated with treatment success (proportion of treatment completed or cured cases). Conclusions

  20. Predictors of Death among Patients Who Completed Tuberculosis Treatment: A Population-Based Cohort Study

    PubMed Central

    Millet, Juan-Pablo; Orcau, Angels; Rius, Cristina; Casals, Marti; de Olalla, Patricia Garcia; Moreno, Antonio; Nelson, Jeanne L.; Caylà, Joan A.

    2011-01-01

    Background Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. Methods A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995–1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 41–60 years old (HR: 3.5; CI:2.1–5.7), age greater than 60 years (HR: 14.6; CI:8.9–24), alcohol abuse (HR: 1.7; CI:1.2–2.4) and HIV-infected IDU (HR: 7.9; CI:4.7–13.3). Conclusions The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival. PMID:21980423

  1. Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis.

    PubMed Central

    Wobeser, W L; Krajden, M; Conly, J; Simpson, H; Yim, B; D'costa, M; Fuksa, M; Hian-Cheong, C; Patterson, M; Phillips, A; Bannatyne, R; Haddad, A; Brunton, J L; Krajden, S

    1996-01-01

    The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial culture, with the BACTEC 460 system and inoculation on Lowenstein-Jensen media. Results were interpreted with an adjusted "gold standard" incorporating clinical diagnosis. A total of 1,480 clinical specimens from 1,155 patients, including tissues and fluids, as well as 141 specimens which demonstrated a positive growth index on the BACTEC 460 system were assessed. The sensitivity, specificity, and positive and negative predictive values of RMtb-PCR compared with the adjusted gold standard for clinical specimens were 79, 99, 93, and 98%, respectively. In smear-positive specimens, the sensitivity of RMtb-PCR was 98% versus 53% for smear-negative specimens. When RMtb-PCR was performed two times per week, PCR results were available an average of 21 days before the culture results. For specimens demonstrating a positive growth index on the BACTEC 460 system, RMtb-PCR had a sensitivity and specificity of 98 and 100%, respectively. This study demonstrates the value of a commercial nucleic acid amplification kit for rapid diagnosis of M. tuberculosis, particularly in smear-positive specimens or BACTEC culture-positive specimens. PMID:8748289

  2. Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): Lessons learnt & challenges ahead

    PubMed Central

    Sharma, Surendra K.; Mohan, Alladi; Chauhan, L.S.; Narain, J.P.; Kumar, P.; Behera, D.; Sachdeva, K.S.; Kumar, Ashok

    2013-01-01

    Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of ‘new smear-positives’ diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement. PMID:23563371

  3. Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model.

    PubMed

    Garcia-Contreras, L; Fiegel, J; Telko, M J; Elbert, K; Hawi, A; Thomas, M; VerBerkmoes, J; Germishuizen, W A; Fourie, P B; Hickey, A J; Edwards, D

    2007-08-01

    Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content. Pharmacokinetic parameters were determined by noncompartmental methods with healthy guinea pigs after administration of capreomycin particles by insufflation. The efficacy of the particles was evaluated by histopathological analysis and in terms of wet organ weight and bacterial burden in TB-infected animals. Lungs of animals receiving a 14.5-mg/kg dose of capreomycin particles showed significantly lower wet weights and smaller bacterial burdens than those of animals receiving any other treatment. These results were supported by histopathological analysis. The feasibility of inhaling capreomycin in a novel powder form, with the ultimate objective of the treatment of MDR-TB, is demonstrated by pharmacokinetic and pharmacodynamic studies with guinea pigs. If applied to humans with MDR-TB, such a therapeutic approach might simplify drug delivery by eliminating injections and might reduce adverse effects through lowering the dose.

  4. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis.

    PubMed

    Pym, Alexander S; Diacon, Andreas H; Tang, Shen-Jie; Conradie, Francesca; Danilovits, Manfred; Chuchottaworn, Charoen; Vasilyeva, Irina; Andries, Koen; Bakare, Nyasha; De Marez, Tine; Haxaire-Theeuwes, Myriam; Lounis, Nacer; Meyvisch, Paul; Van Baelen, Ben; van Heeswijk, Rolf P G; Dannemann, Brian

    2016-02-01

    Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline.Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline.Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively.Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB. PMID:26647431

  5. Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response

    PubMed Central

    Nam, Sung-Jin; Jeong, Jee-Yeong; Jang, Tae-Won; Jung, Mann-Hong; Chun, Bong-Kwon; Cha, Hee-Jae; Oak, Chul-Ho

    2016-01-01

    Background/Aims: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. Methods: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. Results: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. Conclusions: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions. PMID:27271274

  6. Prevention of hepatotoxicity due to anti tuberculosis treatment: A novel integrative approach

    PubMed Central

    Adhvaryu, Meghna R; Reddy, Narsimha M; Vakharia, Bhasker C

    2008-01-01

    AIM: To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity. METHODS: Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result. RESULTS: Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316, P < 0.0001). Mean aspartate transaminase (AST) (195.93 ± 108.74 vs 85 ± 4.24, P < 0.0001), alanine transaminase (ALT) (75.74 ± 26.54 vs 41 ± 1.41, P < 0.0001) and serum bilirubin (5.4 ± 3.38 vs 1.5 ± 0.42, P < 0.0001). A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P = 0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278, P = 0.0037) was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P < 0.0001). CONCLUSION: The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects. PMID:18720535

  7. Incidence and Clinical Outcomes of Clostridium difficile Infection after Treatment with Tuberculosis Medication

    PubMed Central

    Lee, Yu Mi; Huh, Kyu Chan; Yoon, Soon Man; Jang, Byung Ik; Shin, Jeong Eun; Koo, Hoon Sup; Jung, Yunho; Kim, Sae Hee; Moon, Hee Seok; Lee, Seung Woo

    2016-01-01

    Background/Aims To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection. Methods This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication. Results C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26). Conclusions The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status. PMID:26260753

  8. Universal public finance of tuberculosis treatment in India: an extended cost-effectiveness analysis.

    PubMed

    Verguet, Stéphane; Laxminarayan, Ramanan; Jamison, Dean T

    2015-03-01

    Universal public finance (UPF)-government financing of an intervention irrespective of who is receiving it-for a health intervention entails consequences in multiple domains. First, UPF increases intervention uptake and hence the extent of consequent health gains. Second, UPF generates financial consequences including the crowding out of private expenditures. Finally, UPF provides insurance either by covering catastrophic expenditures, which would otherwise throw households into poverty or by preventing diseases that cause them. This paper develops a method-extended cost-effectiveness analysis (ECEA)-for evaluating the consequences of UPF in each of these domains. It then illustrates ECEA with an evaluation of UPF for tuberculosis treatment in India. Using plausible values for key parameters, our base case ECEA concludes that the health gains and insurance value of UPF would accrue primarily to the poor. Reductions in out-of-pocket expenditures are more uniformly distributed across income quintiles. A variant on our base case suggests that lowering costs of borrowing for the poor could potentially achieve some of the health gains of UPF, but at the cost of leaving the poor more deeply in debt.

  9. New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid

    PubMed Central

    Brigden, Grania; Hewison, Cathy; Varaine, Francis

    2015-01-01

    The current treatment for drug-resistant tuberculosis (TB) is long, complex, and associated with severe and life-threatening side effects and poor outcomes. For the first time in nearly 50 years, there have been two new drugs registered for use in multidrug-resistant TB (MDR-TB). Bedaquiline, a diarylquinoline, and delamanid, a nitromidoxazole, have received conditional stringent regulatory approval and have World Health Organization interim policy guidance for their use. As countries improve and scale up their diagnostic services, increasing number of patients with MDR-TB and extensively drug-resistant TB are identified. These two new drugs offer a real opportunity to improve the outcomes of these patients. This article reviews the evidence for these two new drugs and discusses the clinical questions raised as they are used outside clinical trial settings. It also reviews the importance of the accompanying drugs used with these new drugs. It is important that barriers hindering the use of these two new drugs are addressed and that the existing clinical experience in using these drugs is shared, such that their routine-use programmatic conditions is scaled up, ensuring maximum benefit for patients and countries battling the MDR-TB crisis. PMID:26586956

  10. Universal public finance of tuberculosis treatment in India: an extended cost-effectiveness analysis.

    PubMed

    Verguet, Stéphane; Laxminarayan, Ramanan; Jamison, Dean T

    2015-03-01

    Universal public finance (UPF)-government financing of an intervention irrespective of who is receiving it-for a health intervention entails consequences in multiple domains. First, UPF increases intervention uptake and hence the extent of consequent health gains. Second, UPF generates financial consequences including the crowding out of private expenditures. Finally, UPF provides insurance either by covering catastrophic expenditures, which would otherwise throw households into poverty or by preventing diseases that cause them. This paper develops a method-extended cost-effectiveness analysis (ECEA)-for evaluating the consequences of UPF in each of these domains. It then illustrates ECEA with an evaluation of UPF for tuberculosis treatment in India. Using plausible values for key parameters, our base case ECEA concludes that the health gains and insurance value of UPF would accrue primarily to the poor. Reductions in out-of-pocket expenditures are more uniformly distributed across income quintiles. A variant on our base case suggests that lowering costs of borrowing for the poor could potentially achieve some of the health gains of UPF, but at the cost of leaving the poor more deeply in debt. PMID:24497185

  11. Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis

    PubMed Central

    Tupasi, Thelma; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

    2016-01-01

    Abstract Problem New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. Approach We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization – Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Local setting Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Relevant changes Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Lessons learnt Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial. PMID:26908964

  12. Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

    PubMed Central

    Wu, Jiun-Ting; Chiu, Chien-Tung; Wei, Yu-Feng; Lai, Yung-Fa

    2015-01-01

    OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. PMID:26106962

  13. Imaging Manifestations of Thoracic Tuberculosis.

    PubMed

    Restrepo, Carlos Santiago; Katre, Rashmi; Mumbower, Amy

    2016-05-01

    Despite significant improvements in the diagnosis and treatment of tuberculosis achieved during the last 3 decades, tuberculosis still remains one of the deadliest communicable diseases worldwide. Tuberculosis is still present in all regions of the world, with a more significant impact in developing countries. This article reviews the most common imaging manifestations of primary and postprimary tuberculosis, their complications, and the critical role of imaging in the diagnosis and follow-up of affected patients.

  14. [Guidelines for the diagnosis and treatment of latent tuberculosis infection and active tuberculosis in patients with inflammatory joint diseases proposed for treatment with tumour necrosis factor alpha antagonist drugs].

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2006-01-01

    The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-a) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-a therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-a therapy. If the IJD activity requires urgent anti-TNF-a therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-a therapy, even in the presence of a negative test.

  15. Integrating Social Contact and Environmental Data in Evaluating Tuberculosis Transmission in a South African Township

    PubMed Central

    Andrews, Jason R.; Morrow, Carl; Walensky, Rochelle P.; Wood, Robin

    2014-01-01

    Background. Population models of tuberculosis transmission have not accounted for social contact structure and the role of the environment in which tuberculosis is transmitted. Methods. We utilized extensions to the Wells–Riley model of tuberculosis transmission, using exhaled carbon dioxide as a tracer gas, to describe transmission patterns in an endemic community. Drawing upon social interaction data and carbon dioxide measurements from a South African township, we created an age-structured model of tuberculosis transmission in households, public transit, schools, and workplaces. We fit the model to local data on latent tuberculosis prevalence by age. Results. Most tuberculosis infections (84%) were estimated to occur outside of one's own household. Fifty percent of infections among young adults (ages 15–19) occurred in schools, due to high contact rates and poor ventilation. Despite lower numbers of contacts in workplaces, assortative mixing among adults with high rates of smear-positive tuberculosis contributed to transmission in this environment. Households and public transit were important sites of transmission between age groups. Conclusions. Consistent with molecular epidemiologic estimates, a minority of tuberculosis transmission was estimated to occur within households, which may limit the impact of contact investigations. Further work is needed to investigate the role of schools in tuberculosis transmission. PMID:24610874

  16. Safety and effectiveness of CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy for the treatment of pleural tuberculosis

    PubMed Central

    Geng, Shujun; Li, Lijuan; Liu, Jianling; Song, Tao

    2016-01-01

    The aim of the study was to compare the mid- and long-term effects of different treatments such as CT-guided percutaneous pulmonary paracentesis, tuberculoma perfusing chemotherapy and whole-body standard chemotherapy or extended chemotherapy on safety and effectiveness for pleural chemotherapy. A total of 60 subjects diagnosed to have pleural tuberculosis between February 2010 and February 2014 were prospectively selected for this study and were considered as the experimental group. Seventy pleural tuberculosis patients who underwent treatment between February 2006 and February 2010 were considered as the control group. The patients in the experimental group were treated with CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy of not more than three courses with each course consisting of administration of 0.1 g isoniazid, n 0.5 gkanamyci, 0.2 g levofloxacin, and 1 ml lidocaine once a week for four times. The patients in the control group were treated with whole-body standard or extended chemotherapy regimen 3~6HRZE(S)/6~12HR. The patients were followed up for 18 months and the treatment effects were compared. The diameter of tuberculoma in patients of the experimental group during 6, 12 and 18 months was shorter than that of the control group (P<0.05). The total effective rate of treatment and the duration of treatment in experimental group during 18 months were higher than that of control group (P<0.05). The frequency of drug-related complications were lower in comparison with the control group (P<0.05). No surgically acquired complications were observed in the experimental group. Thus, treatments such as CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy for pleural tuberculosis are safe and effective, which has greater value and can be promoted for use in the clinical setting. PMID:27446302

  17. Pulmonary Paragonimiasis Mimicking Tuberculosis.

    PubMed

    Prasad, Kj; Basu, Arup; Khana, Shilpi; Wattal, Chand

    2015-08-01

    Paragonimiasis is a disease which is frequently misdiagnosed as pulmonary tuberculosis. In the areas where people eat crab/crayfish this disease should be considered in the differential diagnosis to avoid antituberculosis treatment for a non-tubercular condition. We are reporting a case of pulmonary paragonimiasis who had been treated for tuberculosis. PMID:27604443

  18. GenoType® Mtbdrsl assay for resistance to second-line anti-tuberculosis drugs

    PubMed Central

    Theron, Grant; Peter, Jonny; Richardson, Marty; Warren, Rob; Dheda, Keertan; Steingart, Karen R

    2016-01-01

    Background Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. Objectives To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. Search methods We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. Selection criteria We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Data collection and analysis Two review authors independently extracted data and assessed

  19. GenoType® Mtbdrsl assay for resistance to second-line anti-tuberculosis drugs

    PubMed Central

    Theron, Grant; Peter, Jonny; Richardson, Marty; Warren, Rob; Dheda, Keertan; Steingart, Karen R

    2016-01-01

    Background Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. Objectives To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. Search methods We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. Selection criteria We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Data collection and analysis Two review authors independently extracted data and assessed

  20. Integrated Pre-Antiretroviral Therapy Screening and Treatment for Tuberculosis and Cryptococcal Antigenemia

    PubMed Central

    Pac, Lincoln; Horwitz, Mara; Namutebi, Anne Marion; Auerbach, Brandon J.; Semeere, Aggrey; Namulema, Teddy; Schwarz, Miriam; Bbosa, Robert; Muruta, Allan; Meya, David; Manabe, Yukari C.

    2015-01-01

    Objective To demonstrate the feasibility of integrated screening for cryptococcal antigenemia and tuberculosis (TB) prior to antiretroviral therapy (ART) initiation and to assess disease specific and all-cause mortality in the first 6 months of follow-up. Methods We enrolled a cohort of HIV-infected, ART-naïve adults with CD4 counts ≤ 250 cells/µL in rural Uganda who were followed for 6 months after ART initiation. All subjects underwent screening for TB; those with CD4 ≤ 100 cells/µL also had cryptococcal antigen (CrAg) screening. For those who screened positive, standard treatment for TB or preemptive treatment for cryptococcal infection was initiated, followed by ART two weeks later. Results Of 540 participants enrolled, pre-ART screening detected 10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count ≤ 100 cells/µL) with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed with TB and one patient developed cryptococcal meningitis. Overall 7.2% of participants died (incidence rate 15.6 per 100 person years at risk). Death rates were significantly higher among subjects with TB and cryptococcal antigenemia compared to subjects without these diagnoses. In multivariate analysis, significant risk factors for mortality were male sex, baseline anemia of hemoglobin ≤ 10 mg/dL, wasting defined as body mass index ≤ 15.5 kg/m2, and opportunistic infections (TB, positive serum CrAg). Conclusion Pre-ART screening for opportunistic infections detects many prevalent cases of TB and cryptococcal infection. However, severely immunosuppressed and symptomatic HIV patients continue to experience high mortality after ART initiation. PMID:25761234

  1. Optimizing outpatient serial sputum colony counting for studies of tuberculosis treatment in resource-poor settings.

    PubMed

    Sloan, Derek J; Corbett, Elizabeth L; Butterworth, Anthony E; Mwandumba, Henry C; Khoo, Saye H; Mdolo, Aaron; Shani, Doris; Kamdolozi, Mercy; Allen, Jenny; Mitchison, Denis A; Coleman, David J; Davies, Geraint R

    2012-07-01

    Serial Sputum Colony Counting (SSCC) is an important technique in clinical trials of new treatments for tuberculosis (TB). Quantitative cultures on selective Middlebrook agar are used to calculate the rate of bacillary elimination from sputum collected from patients at different time points during the first 2 months of therapy. However, the procedure can be complicated by high sample contamination rates. This study, conducted in a resource-poor setting in Malawi, assessed the ability of different antifungal drugs in selective agar to reduce contamination. Overall, 229 samples were studied and 15% to 27% were contaminated. Fungal organisms were particularly implicated, and samples collected later in treatment were at particular risk (P < 0.001). Amphotericin B (AmB) is the standard antifungal drug used on SSCC plates at a concentration of 10 mg/ml. On selective Middlebrook 7H10 plates, AmB at 30 mg/ml reduced sample contamination by 17% compared with AmB at 10 mg/ml. The relative risk of contamination using AmB at 10 mg/ml was 1.79 (95% confidence interval [CI], 1.25 to 3.55). On Middlebrook 7H11 plates, a combination of AmB at 10 mg/ml and carbendazim at 50 mg/ml was associated with 10% less contamination than AmB at 30 mg/ml. The relative risk of contamination with AmB at 30 mg/ml was 1.79 (95% CI, 1.01 to 3.17). Improved antifungal activity was accompanied by a small reduction in bacillary counts, but this did not affect modeling of bacillary elimination. In conclusion, a combination of AmB and carbendazim optimized the antifungal activity of selective media for growth of TB. We recommend this method to reduce contamination rates and improve SSCC studies in African countries where the burden of TB is highest.

  2. Defaulting from tuberculosis treatment in The Netherlands: rates, risk factors and trend in the period 1993-1997.

    PubMed

    Borgdorff, M W; Veen, J; Kalisvaart, N A; Broekmans, J F; Nagelkerke, N J

    2000-08-01

    The aim of this study was to assess the rate of defaulting from treatment among tuberculosis patients diagnosed in the Netherlands in the period 1993-1997, whether risk groups for defaulting can be identified at the start of treatment and the trend of defaulting over time. The Netherlands Tuberculosis Register provided data on all patients diagnosed in the Netherlands during the period 1993-1997. Defaulting probabilities were determined using Kaplan-Meier survival analysis and risk factors were identified with Cox's proportional hazard analysis. Of 7,529 patients with reported treatment outcome, 718 (10%) defaulted or left the country within 1 yr after starting treatment. Defaulting probabilities were 9% (95% confidence interval (CI) 8-10%) among 5,256 patients in low-risk groups, 17% (95% CI 14-19%) among 1,437 asylum seekers and 29% (95% CI 24-34%) among 836 patients in other high-risk groups (other recent immigrants, illegal immigrants, the homeless, prisoners and nationals from Eastern Europe). Defaulting probabilities decreased over time from 12% in 1993 to 7% in 1997. Risk groups for defaulting can be recognized at the start of treatment. The decreasing defaulting probabilities were probably due in part to shortening treatment from 9 to 6 months and improved follow-up of asylum seekers. However, additional measures are needed to reduce defaulting among the homeless, recent immigrants, illegal immigrants and prisoners.

  3. Using Survival Analysis to Identify Risk Factors for Treatment Interruption among New and Retreatment Tuberculosis Patients in Kenya

    PubMed Central

    Masini, Enos O.; Mansour, Omar; Speer, Clare E.; Addona, Vittorio; Hanson, Christy L.; Sitienei, Joseph K.; Kipruto, Hillary K.; Githiomi, Martin Muhingo; Mungai, Brenda Nyambura

    2016-01-01

    Despite high tuberculosis (TB) treatment success rate, treatment adherence is one of the major obstacles to tuberculosis control in Kenya. Our objective was to identify patient-related factors that were associated with time to TB treatment interruption and the geographic distribution of the risk of treatment interruption by county. Data of new and retreatment patients registered in TIBU, a Kenyan national case-based electronic data recording system, between 2013 and 2014 was obtained. Kaplan-Meier curves and log rank tests were used to assess the adherence patterns. Mixed-effects Cox proportional hazards modeling was used for multivariate analysis. Records from 90,170 patients were included in the study. The cumulative incidence of treatment interruption was 4.5% for new patients, and 8.5% for retreatment patients. The risk of treatment interruption was highest during the intensive phase of treatment. Having previously been lost to follow-up was the greatest independent risk factor for treatment interruption (HR: 4.79 [3.99, 5.75]), followed by being HIV-positive not on ART (HR: 1.96 [1.70, 2.26]) and TB relapse (HR: 1.70 [1.44, 2.00]). Male and underweight patients had high risks of treatment interruption (HR: 1.46 [1.35, 1.58]; 1.11 [1.03, 1.20], respectively). High rates of treatment interruption were observed in counties in the central part of Kenya while counties in the northeast had the lowest risk of treatment interruption. A better understanding of treatment interruption risk factors is necessary to improve adherence to treatment. Interventions should focus on patients during the intensive phase, patients who have previously been lost to follow-up, and promotion of integrated TB and HIV services among public and private facilities. PMID:27706230

  4. A Study on the Relapse Rate of Tuberculosis and Related Factors in Korea Using Nationwide Tuberculosis Notification Data

    PubMed Central

    Lee, Hyungmin; Kim, Jusang

    2014-01-01

    Objectives From the perspective of public health, tuberculosis (TB) remains an important issue that threatens health. Korea is an intermediate burden country with a TB incidence of 97/100,000 individuals. Among many TB control measures, a relapse rate of TB is one indicator that can be used to indirectly assess the level of TB control in countries and in communities. Relapse TB has an approximately 12% yearly incidence in Korea. This study aims to estimate the relapse rate of TB and to investigate the associated factors by using nationwide TB notification data in Korea. Methods The nationwide TB notification data in 2005 was used with the exclusion criteria of duplicated reporting, foreign-born patients, outcome–died, and outcome–diagnosis changed. The data were double-checked as to whether they were reported again during 2006–2010 and the estimated relapse rate of TB. Associated factors were analyzed by multivariate logistic regression with the variables of age, sex, registration type, results of sputum smear test, medication, and outcome of treatment. Results Among 45,434 TB patients in 2005, 4,371 patients were again reported as TB patients from 2006 to 2010. Five hundred and sixty-four patients were reported more than twice and the cumulative number of relapses was 5,072 cases. The 5-year relapse rate was estimated as 9.62%. The relapse rate decreased yearly: 4.8% in 2006, 2.4% in 2007, 1.6% in 2008, 1.4% in 2009, and 1.0% in 2010. Age, sex, registration type, tuberculosis type, and medication were independently associated with a relapse of TB. In the multivariate logistic regression analysis, the following factors were related: male sex, 40–49 years old; registration type, relapse, treatment after failure, treatment after default, transfer in, and other, the sputum smear-positive pulmonary TB, and medications (including individuals taking 2–5 drugs). Conclusion This study has estimated a 5-year relapse rate of TB in Korea that is slightly lower than

  5. Treatment Outcomes of New Tuberculosis Patients Hospitalized in Kampala, Uganda: A Prospective Cohort Study

    PubMed Central

    Kirenga, Bruce J.; Levin, Jonathan; Ayakaka, Irene; Worodria, William; Reilly, Nancy; Mumbowa, Francis; Nabanjja, Helen; Nyakoojo, Grace; Fennelly, Kevin; Nakubulwa, Susan; Joloba, Moses; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Mugerwa, Roy D.; Smith, Peter G.; Ellner, Jerrold J.; Jones-López, Edward C.

    2014-01-01

    Background In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda Methods and findings Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 – 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 – 4.01, P = 0.045). Conclusion Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART. PMID:24608875

  6. Month 2 Culture Status and Treatment Duration as Predictors of Recurrence in Pulmonary Tuberculosis: Model Validation and Update

    PubMed Central

    Wallis, Robert S.; Peppard, Thomas; Hermann, David

    2015-01-01

    Background New regimens capable of shortening tuberculosis treatment without increasing the risk of recurrence are urgently needed. A 2013 meta-regression analysis, using data from trials published from 1973 to 1997 involving 7793 patients, identified 2-month sputum culture status and treatment duration as independent predictors of recurrence. The resulting model predicted that if a new 4-month regimen reduced the proportion of patients positive at month 2 to 1%, it would reduce to 10% the risk of a relapse rate >10% in a trial with 680 subjects per arm. The 1% target was far lower than anticipated. Methods Data from the 8 arms of 3 recent unsuccessful phase 3 treatment-shortening trials of fluoroquinolone-substituted regimens (REMox, OFLOTUB, and RIFAQUIN) were used to assess and refine the accuracy of the 2013 meta-regression model. The updated model was then tested using data from a treatment shortening trial reported in 2009 by Johnson et al. Findings The proportions of patients with recurrence as predicted by the 2013 model were highly correlated with observed proportions as reported in the literature (R2 = 0.86). Using the previously proposed threshold of 10% recurrences as the maximum likely considered acceptable by tuberculosis control programs, the original model correctly identified all 4 six-month regimens as satisfactory, and 3 of 4 four-month regimens as unsatisfactory (sensitivity = 100%, specificity = 75%, PPV = 80%, and NPV = 100%). A revision of the regression model based on the full dataset of 66 regimens and 11181 patients resulted in only minimal changes to its predictions. A test of the revised model using data from the treatment shortening trial of Johnson et al found the reported relapse rates in both arms to be consistent with predictions. Interpretation Meta-regression modeling of recurrence based on month 2 culture status and regimen duration can inform the design of future phase 3 tuberculosis clinical trials. PMID:25923700

  7. Characterization and evaluation of the directly observed treatment for tuberculosis in Santiago de Compostela (1996–2006)

    PubMed Central

    Mejuto, Beatriz; Tuñez, Victoria; del Molino, María Luisa Pérez; García, Rosario

    2010-01-01

    Objective To realize a retrospective study of the characterization, results, and effectiveness of directly observed therapy, short course (DOTS) in the regional health area of Santiago de Compostela (population 453 068) between 1996 and 2006. Design Tuberculosis (TB) patient cases involved in DOTS treatment were reviewed. The studied variables included: age, sex, type of TB, TB location, microbiological studies, chest radiology, pattern and treatment duration, final status of case, and TB recurrence. Results There were 2456 diagnosed TB cases in the time period studied and 259 received DOTS. The reasons for inclusion in this treatment strategy were social dystocia in 33.2% of cases, retreatment in 30.8% of cases, alcoholism in 29.3% of cases, drug use in 17.4% of cases, HIV coinfection in 11.6% of cases, multidrug-resistant strains of TB (MDR-TB) in 3.1%, and being an immigrant in 1.9% of cases. Primary TB represented 3.5% of the instances and pulmonary TB represented 87.6%. Bacteriological confirmation was performed in 76.8% of this population. Cavitated forms in chest radiology were shown in 46.7% of patients. Standard treatment guidelines were used in 71.4% of patients. Treatment adherence was achieved in 96.1% of the cases and 86.9% cases had a successful final status. Recurrence of TB was 1.5%. Conclusion Although it is not possible to determine the exact influence of the DOTS strategy, its introduction under the conditions of the Galician Program for Prevention and Control of Tuberculosis (GPPCT)5 has worked to improve the control of tuberculosis in our health area. PMID:22312214

  8. Impact of reduced hospitalisation on the cost of treatment for drug-resistant tuberculosis in South Africa

    PubMed Central

    Sinanovic, E.; Ramma, L.; Vassall, A.; Azevedo, V.; Wilkinson, L.; Ndjeka, N.; McCarthy, K.; Churchyard, G.; Cox, H.

    2015-01-01

    SUMMARY SETTING The cost of multidrug-resistant tuberculosis (MDR-TB) treatment is a major barrier to treatment scale-up in South Africa. OBJECTIVE To estimate and compare the cost of treatment for rifampicin-resistant tuberculosis (RR-TB) in South Africa in different models of care in different settings. DESIGN We estimated the costs of different models of care with varying levels of hospitalisation. These costs were used to calculate the total cost of treating all diagnosed cases of RR-TB in South Africa, and to estimate the budget impact of adopting a fully or partially decentralised model vs. a fully hospitalised model. RESULTS The fully hospitalised model was 42% more costly than the fully decentralised model (US$13 432 vs. US$7753 per patient). A much shorter hospital stay in the decentralised models of care (44–57 days), compared to 128 days of hospitalisation in the fully hospitalised model, was the key contributor to the reduced cost of treatment. The annual total cost of treating all diagnosed cases ranged from US$110 million in the fully decentralised model to US$190 million in the fully hospitalised model. CONCLUSION Following a more decentralised approach for treating RR-TB patients could potentially improve the affordability of RR-TB treatment in South Africa. PMID:25574915

  9. Social Impact of Stigma Regarding Tuberculosis Hindering Adherence to Treatment: A Cross Sectional Study Involving Tuberculosis Patients in Rajshahi City, Bangladesh.

    PubMed

    Chowdhury, Md Rocky Khan; Rahman, Md Shafiur; Mondal, Md Nazrul Islam; Sayem, Abu; Billah, Baki

    2015-01-01

    Stigma, considered a social disease, is more apparent in developing societies which are driven by various social affairs, and influences adherence to treatment. The aim of the present study was to examine levels of social stigma related to tuberculosis (TB) in sociodemographic context and identify the effects of sociodemographic factors on stigma. The study sample consisted of 372 TB patients. Data were collected using stratified sampling with simple random sampling techniques. T tests, chi-square tests, and binary logistic regression analysis were performed to examine correlations between stigma and sociodemographic variables. Approximately 85.9% of patients had experienced stigma. The most frequent indicator of the stigma experienced by patients involved problems taking part in social programs (79.5%). Mean levels of stigma were significantly higher in women (55.5%), illiterate individuals (60.8%), and villagers (60.8%) relative to those of other groups. Chi-square tests revealed that education, monthly family income, and type of patient (pulmonary and extrapulmonary) were significantly associated with stigma. Binary logistic regression analysis demonstrated that stigma was influenced by sex, education, and type of patient. Stigma is one of the most important barriers to treatment adherence. Therefore, in interventions that aim to reduce stigma, strong collaboration between various institutions is essential.

  10. Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment

    PubMed Central

    Liu, Qin; Abba, Katharine; Alejandria, Marissa M; Sinclair, David; Balanag, Vincent M; Lansang, Mary Ann D

    2014-01-01

    Background People with active tuberculosis (TB) require six months of treatment. Some people find it difficult to complete treatment, and there are several approaches to help ensure completion. One such system relies on reminders, where the health system prompts patients to attend for appointments on time, or re-engages people who have missed or defaulted on a scheduled appointment. Objectives To assess the effects of reminder systems on improving attendance at TB diagnosis, prophylaxis, and treatment clinic appointments, and their effects on TB treatment outcomes. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Effective Practice andOrganization of Care Group Specialized Register, CENTRAL,MEDLINE, EMBASE, LILACS, CINAHL, SCI-EXPANDED, SSCI, m RCT, and the Indian Journal of Tuberculosis without language restriction up to 29 August 2014. We also checked reference lists and contacted researchers working in the field. Selection criteria Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing reminder systems with no reminders or an alternative reminder system for people with scheduled appointments for TB diagnosis, prophylaxis, or treatment. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in the included trials. We compared the effects of interventions by using risk ratios (RR) and presented RRs with 95% confidence intervals (CIs). Also we assessed the quality of evidence using the GRADE approach. Main results Nine trials, including 4654 participants, met our inclusion criteria. Five trials evaluated appointment reminders for people on treatment for active TB, two for people on prophylaxis for latent TB, and four for people undergoing TB screening using skin tests.We classified the interventions into 'pre-appointment' reminders (telephone calls or letters prior to a scheduled appointment) or

  11. Evaluation of community-based treatment for drug-resistant tuberculosis in Bangladesh

    PubMed Central

    Cavanaugh, Joseph S.; Kurbatova, Ekaterina; Alami, Negar N.; Mangan, Joan; Sultana, Zinia; Ahmed, Shahriar; Begum, Vikarunessa; Sultana, Sabera; Daru, Paul; Ershova, Julia; Golubkov, Alexander; Banu, Sayera; Heffelfinger, James D.

    2015-01-01

    OBJECTIVE Drug-resistant tuberculosis (TB) threatens global TB control because it is difficult to diagnose and treat. Community-based programmatic management of drug-resistant TB (cPMDT) has made therapy easier for patients, but data on these models are scarce. Bangladesh initiated cPMDT in 2012, and in 2013, we sought to evaluate programme performance. METHODS In this retrospective review, we abstracted demographic, clinical, microbiologic and treatment outcome data for all patients enrolled in the cPMDT programme over 6 months in three districts of Bangladesh. We interviewed a convenience sample of patients about their experience in the programme. RESULTS Chart review was performed on 77 patients. Sputum smears and cultures were performed, on average, once every 1.35 and 1.36 months, respectively. Among 74 initially culture-positive patients, 70 (95%) converted their cultures and 69 (93%) patients converted the cultures before the sixth month. Fifty-two (68%) patients had evidence of screening for adverse events. We found written documentation of musculoskeletal complaints for 16 (21%) patients, gastrointestinal adverse events for 16 (21%), hearing loss for eight (10%) and psychiatric events for four (5%) patients; conversely, on interview of 60 patients, 55 (92%) reported musculoskeletal complaints, 54 (90%) reported nausea, 36 (60%) reported hearing loss, and 36 (60%) reported psychiatric disorders. CONCLUSIONS The cPMDT programme in Bangladesh appears to be programmatically feasible and clinically effective; however, inadequate monitoring of adverse events raises some concern. As the programme is brought to scale nationwide, renewed efforts at monitoring adverse events should be prioritised. PMID:26489698

  12. Tuberculosis Recurrence after Completion Treatment in a European City: Reinfection or Relapse?

    PubMed Central

    Millet, Juan-Pablo; Shaw, Evelyn; Orcau, Àngels; Casals, Martí; Miró, Jose M.; Caylà, Joan A.

    2013-01-01

    Background Tuberculosis (TB) recurrence can be due to reinfection or relapse. The contribution of each to TB incidence and the factors associated with recurrence are not well known. Effectiveness of TB control programs is assessed in part by recurrence rates. The aim of this study was to establish the recurrence rate of TB in Barcelona, the associated risk factors and the role of reinfection. Methods A population-based retrospective longitudinal study was performed in Barcelona, Spain. TB patients with positive culture results who completed treatment between Jan 1st, 2003 and Dec 31st, 2006 were followed-up until December 31st, 2009 by the TB Control Program. The incidence rate of recurrence was calculated per person-year of follow-up (py). Kaplan-Meier and Cox regression methods were used for the survival analysis by calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results Of the 1,823 TB cases identified, 971 fulfilled the inclusion criteria and 13 (1.3%) had recurrent TB. The recurrence rate was 341 cases per 100,000 py, 13 times higher than the TB incidence of the general population. Likelihood of TB recurrence at the 1st, 3rd and 5th year of follow-up was 0.1%, 1.4% and 1.6%, respectively. Factors associated with recurrence were HIV infection (HR: 4.7, CI: 1.4–15.7), living in the inner city district (HR: 3.9, CI: 1.3–11.8) and history of TB treatment (HR: 5.2, CI: 1.7–16.2). Genotyping results of recurrent cases were available for 6 patients (3 reinfections and 3 relapses). Conclusion The rate of TB recurrence in Barcelona is low and most episodes occur within the first three years. Patients at higher risk of recurrence are co-infected with HIV, living in neighborhoods with high TB incidence or with a history of TB treatment. When available, genotyping results help determine whether the recurrence is due to reinfection or relapse. PMID:23776440

  13. Abandonment of Treatment for Latent Tuberculosis Infection and Socioeconomic Factors in Children and Adolescents: Rio De Janeiro, Brazil

    PubMed Central

    Mendonça, Angela Marcia Cabral; Kritski, Afrânio Lineu; Land, Marcelo Gerardin Poirot; Sant’Anna, Clemax Couto

    2016-01-01

    Background Routine data on the use of isoniazid preventive therapy (IPT) in children and adolescents are scarce in high tuberculosis (TB) burden countries. Objective To describe the factors related to abandonment of IPT in children and adolescents with latent tuberculosis infection (LTBI) receiving routine care. Methods Retrospective (2005–2009) descriptive study of 286 LTBI cases with indication of IPT and serviced at a pediatric hospital in the State of Rio de Janeiro, Brazil. Survival analysis of the risk of abandonment of IPT over six months was performed, including multivariate analysis using the Cox proportional hazards model. Results Out of the 245 cases of LTBI included, 62 abandoned IPT (25.3%; 95% CI: 20%-31%). On multivariate analysis, the variables related to the IPT abandonment hazard ratio were the Human Development Index (HDI) (hazard ratio—HR: 0.004; 0.000–0.569) of the place of residence and the contact with adults that were not undergoing anti-TB treatment (HR: 7.30; 1.00–53.3). Conclusion This study reveals the relevance of the relation of abandonment of IPT to the socioeconomic conditions at the place of residence and poor adherence to the active TB treatment. Educational measures to stimulate preventive treatment of child contacts and curative treatment of index cases should target the full familial setting. PMID:27149514

  14. Patterns of Drug Resistance Among Tuberculosis Patients in West and Northwestern Iran

    PubMed Central

    Sahebi, Leyla; Ansarin, Khalil; Mohajeri, Parviz; Khalili, Majid; Monfaredan, Amir; Farajnia, Safar; Zadeh, Simin Khayyat

    2016-01-01

    Background: Tuberculosis (TB) is the leading cause of morbidity and mortality among chronic infectious diseases. Objective: The goal of this cross-sectional study (2011-2013;2013) was to examine the patterns of TB drug resistance among HIV-negative pulmonary TB patients in regions near the Iranian border. Method: To this end, MTB isolates were harvested from 300 HIV-negative, pulmonary smear-positive TB patients from the northwest and west Iranian border provinces. Isolates were subjected to first and second-line drug susceptibility testing by the 1% proportion method. Demographic and clinical data were provided using a questionnaire and information from patient records. Results were analyzed using SPSS-18. Results: The mean age of the patients was 52.03 years and 54.3% were male. The prevalence of resistance to any TB drug was 13.6% (38 cases). Eleven percent of the new treatment TB group (28 patients) and 40.7% of the retreatment TB group (11 patients) were resistant to all TB drugs. Twelve (4.3%) patients had multidrug-resistant tuberculosis (MDR-TB) (2.38% in the new TB treatment group and 23.1% in the retreatment group). One patient had extensively drug-resistant tuberculosis (XDR-TB). There was a statistically significant relationship between TB drug resistance and smoking (p=0.02) and a history of migration from village to city (p=0.04), also between TB drug resistance and recurrence of TB in patients that had previously received treatment (p<0.001). Conclusion: Knowledge of drug resistance patterns for new and previously treated cases is critical for effective control of MDR-TB in different regions of the country. The burden of MDR-TB in retreatment cases was high. Previous TB treatment was one of the most important mokers and those who had a history of rural to urban migration were at high risk for the occurrence of TB drug resistance. PMID:27583054

  15. Transmissibility of Tuberculosis among School Contacts: An Outbreak Investigation in a Boarding Middle School, China

    PubMed Central

    Ma, Mai-Juan; Yang, Yang; Wang, Hai-Bin; Zhu, Yi-Fan; Fang, Li-Qun; An, Xiao-Ping; Wan, Kang-Lin; Whalen, Christopher C.; Yang, Xiao-Xian; Lauzardo, Michael; Zhang, Zhi-Yi; Cao, Jin-Feng; Tong, Yi-Gang; Dai, Er-Hei; Cao, Wu-Chun

    2015-01-01

    Tuberculosis (TB) outbreak occurred in a boarding middle school of China. We explored its probable sources and quantified the transmissibility and pathogenicity of TB. Clinical evaluation, tuberculin skin testing and chest radiography were conducted to identify TB cases. Mycobacterium tuberculosis isolates underwent genotyping analysis to identify the outbreak source. A chain-binomial transmission model was used to evaluate transmissibility and pathogenicity of TB. A total of 46 active cases were ascertained among 258 students and 15 teachers/staff, an attack rate of 16.8%. Genetic analyses revealed two groups of M. tuberculosis cocirculating during the outbreak and possible importation from local communities. Secondary attack rates among students were 4.1% (2.9%, 5.3%) within grade and 7.9% (4.9%, 11%) within class. An active TB case was estimated to infect 8.4 (7.2, 9.6) susceptible people on average. The smear-positive cases were 28 (8, 101) times as infective as smear-negative cases. Previous BCG vaccination could reduce the probability of developing symptoms after infection by 70% (1.4%, 91%). The integration of clinical evaluation, genetic sequencing, and statistical modeling greatly enhanced our understanding of TB transmission dynamics. Timely diagnosis of smear-positive cases, especially in the early phase of the outbreak, is the key to preventing further spread among close contacts. PMID:25757905

  16. Factors Associated with Loss to Follow-up during Treatment for Multidrug-Resistant Tuberculosis, the Philippines, 2012–2014

    PubMed Central

    Garfin, Anna Marie Celina G.; Kurbatova, Ekaterina V.; Mangan, Joan M.; Orillaza-Chi, Ruth; Naval, Leilani C.; Balane, Glenn I.; Basilio, Ramon; Golubkov, Alexander; Joson, Evelyn S.; Lew, Woo-jin; Lofranco, Vivian; Mantala, Mariquita; Pancho, Stuart; Sarol, Jesus N.

    2016-01-01

    To identify factors associated with loss to follow-up during treatment for multidrug-resistant (MDR) tuberculosis (TB) in the Philippines, we conducted a case–control study of adult patients who began receiving treatment for rifampin-resistant TB during July 1–December 31, 2012. Among 91 case-patients (those lost to follow-up) and 182 control-patients (those who adhered to treatment), independent factors associated with loss to follow-up included patients’ higher self-rating of the severity of vomiting as an adverse drug reaction and alcohol abuse. Protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses. These results provide insights for designing interventions aimed at reducing patient loss to follow-up during treatment for MDR TB. PMID:26889786

  17. Latent Tuberculosis Infection in an Urban Cohort: Screening and Treatment for Latent TB in an Urban Setting

    PubMed Central

    Morano, Jamie P.; Walton, Mary R.; Zelenev, Alexei; Bruce, R. Douglas; Altice, Frederick L.

    2013-01-01

    Background Despite its benefit for treating active tuberculosis, directly observed therapy (DOT) for latent tuberculosis infection (LTBI) has been largely understudied among challenging inner city populations. Methods Utilizing questionnaire data from a comprehensive mobile healthcare clinic in New Haven, CT from 2003 to July 2011, a total of 2523 completed tuberculin skin tests (TST’s) resulted in 357 new LTBIs. Multivariate logistic regression correlated covariates of the two outcomes 1) initiation of isoniazid preventative therapy (IPT) and 2) completion of 9-months IPT. Results Of 357 new LTBIs, 86.3% (n=308) completed screening CXRs: 90.3% (n=278) were normal and 0.3% (n=1) with active tuberculosis. Of those completing CXR screening, 44.0% (n=135) agreed to IPT: 69.6% (n=94) selected DOT, and 30.4% (n=41) selected SAT. Initiating IPT was correlated with undocumented status (AOR=3.43; p<0.001) and being born in a country of highest and third highest tuberculosis prevalence (AOR=14.09; p=0.017 and AOR=2.25; p=0.005, respectively). Those selecting DOT were more likely to be Hispanic (83.0% vs 53.7%; p<0.0001), undocumented (57.4% vs 41.5%; p=0.012), have stable housing (p=0.002), employed (p<0.0001), uninsured (p=0.014), no prior cocaine or crack use (p=0.013) and no recent incarceration (p=0.001). Completing 9-months of IPT was correlated with no recent incarceration (AOR 5.95; p=0.036) and younger age (AOR 1.03; p=0.031). SAT and DOT participants did not significantly differ for IPT duration (6.54 vs 5.68 months; p=0.216) nor 9-month completion (59.8% vs 46.3%; p=0.155). Conclusions In an urban mobile healthcare sample, screening completion for LTBI was high with nearly half initiating IPT. Undocumented, Hispanic immigrants from high prevalence tuberculosis countries were more likely to self-select DOT at the mobile outreach clinic, potentially because of more culturally, linguistically, and logistically accessible services and self-selection optimization

  18. Treatment Outcomes for Patients with Extensively Drug-Resistant Tuberculosis, KwaZulu-Natal and Eastern Cape Provinces, South Africa

    PubMed Central

    Cegielski, J. Peter; van der Walt, Martie L.

    2016-01-01

    We analyzed data for a retrospective cohort of patients treated for extensively drug-resistant tuberculosis in 2 provinces in South Africa and compared predictors of treatment outcome in HIV-positive patients who received or had not received antiretroviral drugs with those for HIV-negative patients. Overall, 220 (62.0%) of 355 patients were HIV positive. After 2 years, 34 (10.3%) of 330 patients with a known HIV status and known outcome had a favorable outcome. Multivariate analysis showed that predictors of favorable outcome were negative results for acid-fast bacilli by sputum microscopy at start of treatment and weight >50 kg. HIV-positive patients were more likely to have an unfavorable outcome. The strongest predictor of unfavorable outcome was weight <50 kg. Overall outcomes were poor. HIV status was not a predictor of favorable outcome, but HIV-positive patients were more likely to have an unfavorable outcome. These results underscore the need for timely and adequate treatment for tuberculosis and HIV infection. PMID:27538119

  19. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB.

    PubMed

    Barr, David A; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R; Sloan, Derek J

    2016-05-01

    Faster elimination of drug tolerant 'persister' bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates 'persister' phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli.

  20. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB

    PubMed Central

    Barr, David A.; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R.; Sloan, Derek J.

    2016-01-01

    Summary Faster elimination of drug tolerant ‘persister’ bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates ‘persister’ phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli. PMID:27156626

  1. High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

    PubMed Central

    Jindani, Amina; Harrison, Thomas S.; Nunn, Andrew J.; Phillips, Patrick P.J.; Churchyard, Gavin J.; Charalambous, Salome; Hatherill, Mark; Geldenhuys, Hennie; McIlleron, Helen M.; Zvada, Simbarashe P.; Mungofa, Stanley; Shah, Nasir A.; Zizhou, Simukai; Magweta, Lloyd; Shepherd, James; Nyirenda, Sambayawo; van Dijk, Janneke H.; Clouting, Heather E.; Coleman, David; Bateson, Anna L.E.; McHugh, Timothy D.; Butcher, Philip D.; Mitchison, Denny A.

    2014-01-01

    BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and

  2. Detection of Mycobacterium tuberculosis (MTB) in Fecal Specimens From Adults Diagnosed With Pulmonary Tuberculosis Using the Xpert MTB/Rifampicin Test

    PubMed Central

    Kokuto, Hiroyuki; Sasaki, Yuka; Yoshimatsu, Shoji; Mizuno, Kazue; Yi, Lina; Mitarai, Satoshi

    2015-01-01

    Background. The Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) is a fully automated diagnostic test that allows for the detection of MTB including its RIF resistance. Although the test is used for the diagnosis of tuberculosis (TB) in sputum samples worldwide, studies using fecal specimens are scarce. We therefore evaluated the efficacy of the Xpert MTB/RIF test for detection of MTB in fecal specimens obtained from adult pulmonary TB patients, confirmed by culture and/or molecular diagnostic methods. Methods. We conducted a retrospective case-control study to provide proof-of-concept regarding the efficacy of the Xpert MTB/RIF test using fecal samples for diagnosing pulmonary TB via detection of MTB in adult patients (≥20 years) at the Fukujuji Hospital in Tokyo, Japan. Results. Fecal specimens were obtained from 56 active pulmonary TB patients (including 48 sputum smear-positive and 8 sputum smear-negative patients), 10 non-TB patients (including 4 Myocobacterium avium complex infections), and 27 healthy individuals who were exposed to active pulmonary TB patients. The sensitivity of the fecal Xpert MTB/RIF was 100% (81.7%–100%) for detection of MTB in specimens from sputum smear-positive (1+ to 3+) patients, 81.0% (58.1%–94.6%) in specimens from sputum smear scanty positive patients, and 50.0% (15.7%–84.3%) in specimens from sputum smear-negative patients. Meanwhile, each of the fecal specimens from the non-TB group was negative for MTB (specificity 100%; 95% confidence interval, 86.2–100). Conclusions. The fecal Xpert MTB/RIF test could detect MTB in a large proportion of smear-positive pulmonary TB patients, without frequent false-positive results at a TB referral hospital in Japan. PMID:26125035

  3. Seasonality of Tuberculosis

    PubMed Central

    Fares, Auda

    2011-01-01

    Objectives: This study was designed to review previous studies and analyse the current knowledge and controversies related to seasonal variability of tuberculosis (TB) to examine whether TB has an annual seasonal pattern. Study Design and Methods: Systematic review of peer reviewed studies identified through literature searches using online databases belonging to PubMed and the Cochrane library with key words “Tuberculosis, Seasonal influence” and “Tuberculosis, Seasonal variation”. The search was restricted to articles published in English. The references of the identified papers for further relevant publications were also reviewed. Results: Twelve studies conducted between the period 1971 and 2006 from 11 countries/regions around the world (South Western Cameroon, South Africa, India, Hong Kong, Japan, Kuwait, Spain, UK, Ireland, Russia, and Mongolia) were reviewed. A seasonal pattern of tuberculosis with a mostly predominant peak is seen during the spring and summer seasons in all of the countries (except South Western Cameroon and Russia). Conclusions: The observation of seasonality leads to assume that the risk of transmission of M. tuberculosis does appear to be the greatest during winter months. Vitamin D level variability, indoor activities, seasonal change in immune function, and delays in the diagnosis and treatment of tuberculosis are potential stimuli of seasonal tuberculosis disease. Additionally, seasonal variation in food availability and food intake, age, and sex are important factors which can play a role in the tuberculosis notification variability. Prospective studies regarding this topic and other related subjects are highly recommended. PMID:21572609

  4. Call for Increased Patient Support Focus: Review and Evaluation of Mobile Apps for Tuberculosis Prevention and Treatment.

    PubMed

    Iribarren, Sarah; Schnall, Rebecca

    2016-01-01

    Tuberculosis (TB) remains a major global public health problem and is a leading killer due to an infectious disease. Mobile applications (apps) could support TB prevention and treatment. App stores were searched and of the 1332 reviewed 24 met our inclusion criteria. For each app 11 functionalities were assessed. The majority were targeted towards clinicians (n=17), few patient focused (n=4). Most had fewer than 4 functions out of 11, inform and record being the highest. Peer reviewed publications were identified for 2 of the apps and 3 apps in testing stage were found in the grey literature. Apps for TB prevention and treatment had minimal functionality, primarily targeted clinicians, and focused on information or data collection. None were for patient self-management of care and treatment or to improve patient-provider interactions. Identifying TB patient needs and involving them in the design phase is recommended. PMID:27332418

  5. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis.

    PubMed

    Cilfone, N A; Pienaar, E; Thurber, G M; Kirschner, D E; Linderman, J J

    2015-03-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  6. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  7. Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative.

    PubMed

    Nathanson, E; Gupta, R; Huamani, P; Leimane, V; Pasechnikov, A D; Tupasi, T E; Vink, K; Jaramillo, E; Espinal, M A

    2004-11-01

    Adverse events associated with second-line drugs have been mentioned as obstacles in the management of multidrug-resistant tuberculosis (MDR-TB). Data on adverse events were collected from five DOTS-Plus sites in Estonia, Latvia, Peru (Lima), the Philippines (Manila) and the Russian Federation (Tomsk Oblast). The results show that among 818 patients enrolled on MDR-TB treatment only 2% of patients stopped treatment, but 30% required removal of the suspected drug(s) from the regimen due to adverse events. The study shows that adverse events are manageable in the treatment of MDR-TB in resource-limited settings provided that standard management strategies are applied. PMID:15581210

  8. Nurses' Roles and Experiences with Enhancing Adherence to Tuberculosis Treatment among Patients in Burundi: A Qualitative Study

    PubMed Central

    Carlsson, Marie; Johansson, Stina; Eale, Remy-Paul Bosela

    2014-01-01

    Background. In TB control, poor treatment adherence is a major cause of relapse and drug resistance. Nurses have a critical role in supporting patients in TB treatment process. Yet, very little research has been done to inform policymakers and practitioners on nurses' experiences of treatment adherence among patients with TB. Aim. To describe nurses' experiences of supporting treatment adherence among patients with tuberculosis in Burundi. Method. The study adopted qualitative approach with a descriptive design. A purposive sampling was performed. Eight nurses were selected from two TB treatment centers in Burundi. Content analysis was used to analyze the data. Result. According to the nurses, most patients complete their treatment. Educating patients, providing the medication, observing and following up treatment, and communicating with the patients were the key tasks by nurses to support adherence. Causes for interruption were medication-related difficulties, poverty, and patients' indiscipline. Treatment adherence could also be affected by patients' and nurses' feelings. Providing transportation and meals could enhance treatment compliance. Conclusion. Nurses are critical resources to TB treatment success. In a poverty stricken setting, nurses' work could be facilitated and adherence further could be enhanced if socioeconomic problems (transportation and nutritional support) were alleviated. PMID:25215232

  9. Effect of antitubercular treatment on ovarian function in female genital tuberculosis with infertility

    PubMed Central

    Sharma, Jai Bhagwan; Sneha, J.; Singh, U. B.; Kumar, Sunesh; Roy, K. K.; Singh, Neeta; Dharmendra, Sona

    2016-01-01

    AIM: To evaluate the effect of antitubercular therapy (ATT) on an ovarian function such as ovarian reserve, ovarian dimensions, and ovarian stromal blood flow. SETTINGS AND DESIGN: Prospective study design. MATERIALS AND METHODS: Fifty infertile women with female genital tuberculosis (FGTB) without tubo-ovarian masses diagnosed by positive acid-fast bacilli culture or epithelioid granuloma on endometrial aspirate or positive polymerase chain reaction with positive findings on laparoscopy or hysteroscopy were recruited. The ovarian function tests were performed on day 2/3 as follicle-stimulating hormone (FSH) levels and anti-Mullerian hormone (AMH) levels. Ovarian dimensions (length, width, and depth) were measured using a transvaginal ultrasound. Mean antral follicle count (AFC) and ovarian stromal blood flow (peak systolic velocity [PSV], pulsatility index (PI), and resistive index [RI]) were measured using a transvaginal ultrasound. All women were started on ATT for 6 months by directly observed treatment strategy. After completion of ATT, all the parameters were repeated. RESULTS: There was a significant increase in AMH (2.68 ± 0.97 ng/ml to 2.8 ± 1.03 ng/ml) pre- to post-ATT, nonsignificant increase in FSH (7.16 ± 2.34 mIU/ml to 7.26 ± 2.33 mIU/ml) post-ATT, significant increase in mean AFC (7.40 ± 2.12–8.14 ± 2.17), PSV in the right ovary (6.015–6.11 cm/s) and left ovary (6.05–6.08 cm/s), PI in the right ovary (0.935–0.951 cm/s) and left ovary (0.936–0.957 cm/s), and RI in the right ovary (0.62 ± 0.01–0.79 ± 0.02) and left ovary (0.65 ± 0.02–0.84 ± 0.01) with ATT. There was no significant change in mean ovarian dimensions (ovarian length, breadth, and width) and summed ovarian volume with ATT. On laparoscopy, tubercles were seen in 27 (54%) women. Caseous nodules and encysted ascites were seen in 8% cases each. CONCLUSION: ATT improves the ovarian function (AMH and AFC) and ovarian blood flow in women with FGTB. PMID:27803581

  10. Home Videophones Improve Direct Observation in Tuberculosis Treatment: A Mixed Methods Evaluation

    PubMed Central

    Wade, Victoria A.; Karnon, Jonathan; Eliott, Jaklin A.; Hiller, Janet E.

    2012-01-01

    Background The use of direct observation to monitor tuberculosis treatment is controversial: cost, practical difficulties, and lack of patient acceptability limit effectiveness. Telehealth is a promising alternative delivery method for improving implementation. This study aimed to evaluate the clinical and cost-effectiveness of a telehealth service delivering direct observation, compared to an in-person drive-around service. Methodology/Principal Findings The study was conducted within a community nursing service in South Australia. Telehealth patients received daily video calls at home on a desktop videophone provided by the nursing call center. A retrospective cohort study assessed the effectiveness of the telehealth and traditional forms of observation, defined by the proportion of missed observations recorded in case notes. This data was inputted to a model, estimating the incremental cost-effectiveness ratio (ICER) of telehealth. Semi-structured interviews were conducted with current patients, community nursing and Chest Clinic staff, concerning service acceptability, usability and sustainability. The percentage of missed observations for the telehealth service was 12.1 (n = 58), compared to 31.1 for the in-person service (n = 70). Most of the difference of 18.9% (95% CI: 12.2 – 25.4) was due to fewer pre-arranged absences. The economic analysis calculated the ICER to be AUD$1.32 (95% CI: $0.51 – $2.26) per extra day of successful observation. The video service used less staff time, and became dominant if implemented on a larger scale and/or with decreased technology costs. Qualitative analysis found enabling factors of flexible timing, high patient acceptance, staff efficiency, and Chest Clinic support. Substantial technical problems were manageable, and improved liaison between the nursing service and Chest Clinic was an unexpected side-benefit. Conclusions/Significance Home video observation is a patient-centered, resource efficient way of

  11. A Sterilizing Tuberculosis Treatment Regimen Is Associated with Faster Clearance of Bacteria in Cavitary Lesions in Marmosets

    PubMed Central

    Via, Laura E.; England, Kathleen; Weiner, Danielle M.; Schimel, Daniel; Zimmerman, Matthew D.; Dayao, Emmanuel; Chen, Ray Y.; Dodd, Lori E.; Richardson, Mike; Robbins, Katherine K.; Cai, Ying; Hammoud, Dima; Herscovitch, Peter; Dartois, Véronique; Flynn, JoAnne L.

    2015-01-01

    Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated Mycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P = 0.035) and also significantly reduced uptake of [18F]-2-fluoro-2-deoxyglucose by positron emission tomography (P = 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P = 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation. PMID:25941223

  12. A sterilizing tuberculosis treatment regimen is associated with faster clearance of bacteria in cavitary lesions in marmosets.

    PubMed

    Via, Laura E; England, Kathleen; Weiner, Danielle M; Schimel, Daniel; Zimmerman, Matthew D; Dayao, Emmanuel; Chen, Ray Y; Dodd, Lori E; Richardson, Mike; Robbins, Katherine K; Cai, Ying; Hammoud, Dima; Herscovitch, Peter; Dartois, Véronique; Flynn, JoAnne L; Barry, Clifton E

    2015-07-01

    Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated Mycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P = 0.035) and also significantly reduced uptake of [(18)F]-2-fluoro-2-deoxyglucose by positron emission tomography (P = 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P = 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation. PMID:25941223

  13. Tuberculosis