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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

    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

  3. 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

  4. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26729141

  6. [Prevalence of smear-positive pulmonary tuberculosis in Aïoun hospital (Hodh El Garbi)].

    PubMed

    Boushab, B M; Savadogo, M; Sow, M S

    2016-08-01

    In this retrospective study in the regional hospital Aioun from 1st January 2010 to 31st April 2014, the objective was to determine the prevalence of smear-positive PTB. In total, 320 cases have been identified giving a proportion of 9%. The male subjects (74%) were three times higher than for female subjects with a sex-ratio man/woman of 2.8. The average age of patients was 41±16 years with extremes of 15 and 90 years and the most affected age group was 15-30 years (41%). The majority of our patients (85%) came from rural areas. No patient had been screened for HIV infection. There was a statistically significant relationship between gender, age group (P=0.005) and resistant cases after 6months of anti-TB treatment (P=0.04). Tuberculosis remains a public health problem in our country. Many efforts will still be provided for screening and epidemiological surveillance for a good control of the disease. PMID:26655445

  7. Survival of smear-positive multidrug resistant tuberculosis patients in Witbank, South Africa: A retrospective cohort study.

    PubMed

    Olaleye, Abiola O; Beke, Andy K

    2016-06-01

    Background A retrospective cohort study was carried out to compare the survival between smear-positive patients and smear-negative multidrug resistant tuberculosis (MDR-TB) patients hospitalised in a specialised TB hospital in Witbank, South Africa. Methods A review of medical records of MDR-TB patients treated from 2001 to 2010 was carried out. Survival time was measured from a patient's date of hospitalisation to the date when the patient died, was last treated at the hospital or the end of the study (whichever came first). All patients who were alive until the end of the study period or lost to follow-up were censored and those who died were considered as failures. Survival patterns were estimated using Kaplan Meier plots, log rank tests and life tables. Cox proportional hazards regression analyses were also conducted. Results The mean age of the 442 MDR-TB patients in the study was 37.7 ± 11.2 years. The incidence rates of mortality were 13.4 and 43.9 per 1000 person-months for smear-negative and smear-positive MDR-TB patients, respectively. Cox proportional hazard regression showed that the predictors of death among MDR-TB patients include HIV co-infection (adjusted Hazard Rate, aHR = 1.89, 95% CI = 1.02-3.52), old age (above 60 years) (aHR = 2.05, 95% CI = 1.04-3.60) and smear positivity at diagnosis (aHR = 3.29, 95% CI = 2.39-4.64). Conclusion The study showed that the probability of survival during the treatment is reduced in MDR-TB patients, who are smear-positive, HIV positive or older than 60 years. Special care should be given to these patients to improve survival. PMID:26954520

  8. 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

  9. The Prevalence of Latent Tuberculosis Infection and Smear Positive Pulmonary Tuberculosis in People with Household Close Contact with Tuberculosis in North of Iran

    PubMed Central

    Moosazadeh, Mahmood; Khanjani, Narges; Parsaee, Mohammadreza

    2015-01-01

    One of the recommended strategies for preventing tuberculosis is to screen high-risk populations with respect to Mycobacterium tuberculosis (TB) infection. The aim of the present study was to investigate latent infection and active tuberculosis in people with close household contact. It was a cross-sectional descriptive, analytical study with the sample size of 668 people from homes with one infected resident. In order to diagnose tuberculosis latent infection, the PPD test was done. To determine patients with smear-positive pulmonary tuberculosis, three sputum samples were taken from every patient and were examined using direct microscopy and culture. Data was analyzed by SPSS20 software. The prevalence of latent tuberculosis infection and smear-positive pulmonary tuberculosis were 42.8% and 0.9% respectively. The prevalence of latent tuberculosis infection and smear-positive pulmonary tuberculosis in people with close household contact were less than that of other studies. However, smear-positive pulmonary tuberculosis in people with close household contact was 199.5 times more than that of the general population. PMID:25821296

  10. 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

  11. Evaluation of the relationship between smear positivity and high-resolution CT findings in children with pulmonary tuberculosis

    PubMed Central

    Bolursaz, Mohammad Reza; Mehrian, Payam; Aghahosseini, Farahnaz; Lotfian, Ferial; Khalilzadeh, Soheila; Baghaie, Nooshin; Hassanzad, Maryam; Velayati, Ali Akbar

    2014-01-01

    Summary Background The aim of this study is to find a relationship between the radiological manifestations of childhood tuberculosis on a high-resolution computed tomography (HRCT) and the results of sputum smear. This study aims to propose an alternative indicator of infectivity in terms of prevention of disease transmission through selective isolation policy in children whose clinical condition is highly suggestive of tuberculosis. Material/Methods This retrospective comparative study was performed on 95 children under 15 years of age diagnosed with tuberculosis based on both WHO criteria and positive sputum culture for mycobacterium Tuberculosis. The children were admitted for TB screening in the pediatric department of national research institute of tuberculosis and lung disease (NRITLD) between 2008–2012. Direct smear collected from sputum or gastric lavage, as well as HRCT were performed in all children prior to administration of medical therapy. Children were divided into 2 groups based on positive and negative smear results. HRCT abnormalities, as well as their anatomical distribution were compared between these 2 groups using multivariate analytic model. Results The most prevalent abnormalities in the positive smear group were consolidation, tree-in-bud pattern, upper lobe nodular infiltration and cavitation. The negative smear group featured lymphadenopathy, consolidation, collapse and nodular infiltration in the upper lobe. Cavity, tree- in-bud pattern and upper lobe nodular infiltration were highly associated with smear positivity in children. Conversely, lymphadenopathy and collapse had significant association with a negative smear. Conclusions This study revealed that cavity, tree-in-bud and upper lobe nodular infiltration has significant association with smear positivity in childhood tuberculosis. On the other hand, lymphadenopathy and collapse were closely associated with smear negativity in this age group. It was also demonstrated that children

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Household symptomatic contact screening of newly diagnosed sputum smears positive tuberculosis patients - An effective case detection tool

    PubMed Central

    Gupta, Mridul; Saibannavar, Anita A; Kumar, Vinod

    2016-01-01

    Objectives: Primary objective was to assess the prevalence of tuberculosis (TB) among household contacts of newly diagnosed sputum smear (SS) positive TB index cases. Secondary objectives were the evaluation of risk factors in household contacts for acquiring TB disease; and the evaluation of various characteristics of index cases which influence the transmission of disease to household contacts. Settings and Design: This exploratory cohort study included 521 household contacts of 133 newly diagnosed SS positive TB patients who were registered under the Revised National Tuberculosis Control Program at the Directly Observed Treatment-Short Course Centres of District Tuberculosis Centre, Kolhapur, Maharashtra from July 1, 2013 to February 28, 2014 (8 months). Subjects and Methods: Household contacts with symptoms suggestive to TB were subjected to SS examination of two samples for acid fast bacilli by Ziehl-Neelsen staining and for X-ray chest postero-anterior view. Presence of risk factors in symptomatic contacts was also recorded. Results: Eighteen contacts out of 521 (3.45%) had symptoms suggestive of TB. Of these, 6 contacts were diagnosed to have TB; 5 being sputum positive cases and one with X-ray suggestive of TB; giving a prevalence of 1.15 %. The study achieved a yield of 4.51% secondary cases. Conclusions: Household contact screening of newly diagnosed TB index cases provides modest yield of cases. Relatively fewer secondary symptomatic persons need to be investigated by this method for achieving additional yield proving it to be a practical and feasible approach. PMID:27051103

  18. Access to Bacteriologic-Based Diagnosis in Smear Positive Retreatment Tuberculosis Patients in Rural China: A Cross-Sectional Study in Three Geographic Varied Provinces

    PubMed Central

    Zhou, Changming; Jiang, Weili; Yuan, Li; Lu, Wei; He, Jinge; Zhao, Qi; Xu, Biao

    2016-01-01

    Objective To determine factors influencing the utilization and accessibility to bacteriologic-based tuberculosis (TB) diagnosis among sputum smear positive (SS+) retreatment TB patients, and to develop strategies for improving the case detection rate of MDR-TB in rural China. Study Design and Setting A cross-sectional study of SS+ TB retreatment patients was conducted in eight counties from three provinces with different implementation period and strategy of MDR-TB program in China. Demographic and socioeconomic parameters were collected by self-reporting questionnaires. Sputum samples were collected and cultured by the laboratory of county-designated TB clinics and delivered to prefectural Centers for Disease Prevention and Control (CDC) labs for DST with 4 first-line anti-TB drugs. Results Among the 196 SS+ retreatment patients, 61.22% received culture tests during current treatment. Patients from more developed regions (OR = 24.0 and 3.6, 95% CI: 8.6–67.3 and 1.1–11.6), with better socio-economic status (OR = 3. 8, 95% CI: 1.3–10.7), who had multiple previous anti-TB treatments (OR = 5.0, 95% CI: 1.6–15.9), and who failed in the most recent anti-TB treatment (OR = 2.6, 95% CI: 1.0–6.4) were more likely to receive culture tests. The percentage of isolates resistant to any of first-line anti-TB drugs and MDR-TB were 50.0% (95% CI: 39.8%-60.2%) and 30.4% (95% CI: 21.0%-39.8%) respectively. Conclusions Retreatment SS+ TB patients, high risk MDR-TB population, had poor utilization of access to bacteriologic-based TB diagnosis, which is far from optimal. The next step of anti-TB strategy should be focused on how to make bacteriological-based diagnosis cheaper, safer and more maneuverable, and how to assure the DST-guided treatment for these high-risk TB patients. PMID:26751583

  19. Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity

    PubMed Central

    Abate, Ebba; Belayneh, Meseret; Idh, Jonna; Diro, Ermias; Elias, Daniel; Britton, Sven; Aseffa, Abraham; Stendahl, Olle; Schön, Thomas

    2015-01-01

    Background The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB. Methodology Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively. Results A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13–103) versus 2 SFU (1–50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2–16.7) cells/μl versus 2.4 (1.1–4.0) cells/μl; p = 0.041) and IL-10 secreting cells (65 SFU (7–196) versus 1 SFU (0–31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients. Conclusions Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients. PMID:26248316

  20. Diagnostic Accuracy of In-House PCR for Pulmonary Tuberculosis in Smear-Positive Patients: Meta-Analysis and Metaregression▿ †

    PubMed Central

    Greco, S.; Rulli, M.; Girardi, E.; Piersimoni, C.; Saltini, C.

    2009-01-01

    In-house PCR (hPCR) could speed differential diagnosis between tuberculosis (TB) and nontuberculous mycobacterial disease in patients with positive smears and pulmonary infiltrates, but its reported accuracy fluctuates across studies. We conducted a systematic review and meta-analysis of hPCR sensitivity and specificity for smear-positive TB diagnosis, using culture as the reference standard. After searching English language studies in MEDLINE and EMBASE, we estimated cumulative accuracy by means of summary receiver operating characteristic analysis. The possible influence of hPCR procedures and study methodological features on accuracy was explored by univariate metaregression, followed by multivariate adjustment of items selected as significant. Thirty-five articles (1991 to 2006) met the inclusion criteria. The pooled estimates of the diagnostic odds ratio, sensitivity, and specificity (random-effect model) were, respectively, 60 (confidence interval [CI], 29 to 123), 0.96 (CI, 0.95 to 0.97), and 0.81 (CI, 0.78 to 0.84), but significant variations (mainly in specificity) limit their clinical applicability. The quality of the reference test, the detection method, and real-time PCR use explained some of the observed heterogeneity. Probably due to the limited study power of our meta-analysis and to the wide differences in both laboratory techniques and methodological quality, only real-time PCR also displayed a positive impact on accuracy in the multivariate model. Currently, hPCR can be confidently used to exclude TB in smear-positive patients, but its low specificity could lead to erroneous initiation of therapy, isolation, and contact investigation. As the inclusion of samples from treated patients could have artificially reduced specificity, future studies should report mycobacterial-culture results for each TB and non-TB sample analyzed. PMID:19144797

  1. 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

  2. Evaluation of the GenoType Mycobacteria Direct assay for the simultaneous detection of the Mycobacterium tuberculosis complex and four atypical mycobacterial species in smear-positive respiratory specimens.

    PubMed

    Seagar, A-Louise; Prendergast, Carmel; Emmanuel, F Xavier; Rayner, Alan; Thomson, Susan; Laurenson, Ian F

    2008-05-01

    A novel, commercially available reverse hybridization assay [GenoType Mycobacteria Direct (GTMD), version 2.0; Hain Lifescience] was evaluated for the direct detection of five clinically relevant mycobacterial species [Mycobacterium tuberculosis complex (MTBC), Mycobacterium avium, Mycobacterium malmoense, Mycobacterium kansasii and Mycobacterium intracellulare] from 54 smear-positive respiratory specimens and the findings were compared with culture results. Three approaches were used for specimen preparation using either whole or 'split' sample volumes and N-acetyl-l-cysteine/3 % NaOH or 4 % NaOH as decontamination chemicals. Forty-three out of 52 samples in which RNA amplification was successful gave GTMD results that concurred with the identification of the cultured isolate. All cases of MTBC were detected. Twenty-two samples contained M. tuberculosis complex, seven had M. kansasii, four had M. malmoense, seven contained atypical mycobacteria other than those detectable using the GTMD assay and three specimens contained no viable mycobacteria. The assay is easy to use and can be completed in one working day. Results interpretation is facilitated by the inclusion of an internal amplification control with each sample to allow identification of specimens containing amplification inhibitors. A positive GTMD result will quickly identify patients with MTBC infection or provide specific identification of four other atypical mycobacteria from the same specimen. This allows more rapid drug susceptibility testing, treatment, and public health and infection control decisions. PMID:18436594

  3. 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

  4. Identification of Mycobacterium tuberculosis and M. avium complex directly from smear-positive sputum specimens and BACTEC 12B cultures by high-performance liquid chromatography with fluorescence detection and computer-driven pattern recognition models.

    PubMed

    Jost, K C; Dunbar, D F; Barth, S S; Headley, V L; Elliott, L B

    1995-05-01

    A high-performance liquid chromatography method that utilized fluorescence detection (HPLC-FL) of mycolic acid 6,7-dimethoxycoumarin esters was developed to identify Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) directly from fluorochrome stain smear-positive sputum specimens and young BACTEC 12B cultures. HPLC-FL chromatograms from a training set that included 202 smear-positive clinical sputum specimens and 343 mycobacterial cultures were used to construct a calibrated peak-naming table and computer-based pattern recognition models for MTB and MAC. Pattern recognition model performance was measured with an evaluation set of samples that included 251 smear-positive clinical sputum specimens and 167 BACTEC 12B cultures. Evaluation sputum specimens were culture positive for MTB (n = 132) and MAC (n = 48). With evaluation sputa, the MTB and MAC models were 56.8 and 33.3% sensitive, respectively. Evaluation set BACTEC 12B cultures were culture positive for MTB (n = 97) and MAC (n = 53). The sensitivities of the MTB and MAC models for identification of BACTEC 12B cultures were 99.0 and 94.3%, respectively. The specificity of both models was 100% for both types of evaluation samples. The average times from BACTEC 12B inoculation to cell harvest were 10.2 and 7.4 days for MTB and MAC, respectively. HPLC-FL can identify MTB and MAC in 1 day from many smear-positive sputa. Rapid and sensitive identification of MTB and MAC from young BACTEC 12B cultures was achieved. PMID:7615740

  5. Variation in Gamma Interferon Responses to Different Infecting Strains of Mycobacterium tuberculosis in Acid-Fast Bacillus Smear-Positive Patients and Household Contacts in Antananarivo, Madagascar▿

    PubMed Central

    Rakotosamimanana, Niaina; Raharimanga, Vaomalala; Andriamandimby, Soa Fy; Soares, Jean-Louis; Doherty, T. Mark; Ratsitorahina, Maherisoa; Ramarokoto, Herimanana; Zumla, Alimuddin; Huggett, Jim; Rook, Graham; Richard, Vincent; Gicquel, Brigitte; Rasolofo-Razanamparany, Voahangy

    2010-01-01

    The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-γ) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-γ production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo, Madagascar, from 2004 to 2006 and examined the influence of the infecting M. tuberculosis strains on this response. The cohorts were sputum-positive index cases and their household contacts. Clinical strains isolated from the TB patients were typed by spoligotyping. Comparison of the IFN-γ responses with the spoligotype of the infecting clinical strains showed that “modern” M. tuberculosis strains, like Beijing and Central Asian (CAS) strains, tended to induce lower IFN-γ responses than “ancient” strains, like East African-Indian (EAI) strains, in index cases and their household contacts. These results suggest that new strains may have evolved to induce a host response different from that of ancient strains. These findings could have important implications in the development of therapeutic and diagnostic strategies. PMID:20463103

  6. 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, ...

  7. Effect of Diagnostic and Treatment Delay on the Risk of Tuberculosis Transmission in Shenzhen, China: An Observational Cohort Study, 1993–2010

    PubMed Central

    Yang, Yingzhou; Chu, Ping; Liu, Xiaoli; Zhao, Meigui; Tan, Weiguo; Xu, Li; Wu, Qingfang; Guan, Hongyun; Liu, Jinhong; Liu, Haitao; Chen, Ray Y.; Jia, Zhongwei

    2013-01-01

    Introduction To understand better the risk of tuberculosis transmission with increasing delay in tuberculosis treatment, we undertook a retrospective cohort study in Shenzhen, China. Methods All pulmonary tuberculosis cases in the Shenzhen tuberculosis surveillance database from 1993–2010 were included. Sputum smear positivity and presence of pulmonary cavity were used as proxies for risk of tuberculosis transmission. Results Among 48,441pulmonary tuberculosis cases, 70% presented with symptoms of pulmonary TB, 62% were sputum smear positive, and 21% had a pulmonary cavity on chest x-ray. 95.3% of patients self-presented for evaluation of illness after a median 58 days of delay after symptoms began. The proportion presenting sputum smear positive (p<0.001) and with a pulmonary cavity (p<0.001) increased significantly with increasing duration of delay. Conclusions Delayed diagnosis and treatment of tuberculosis is associated with a significantly increased risk of pulmonary sputum smear positivity and pulmonary cavity. To decrease risk of transmission, treatment delay needs to be reduced further. PMID:23826313

  8. Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals, Uganda

    PubMed Central

    Reid, A. J.; Fujiwara, P. I.; Mugabe, F.; Kosgei, R. J.; Tayler-Smith, K.; Kizito, W.; Joloba, M.

    2013-01-01

    Setting: Three regional referral hospitals in Uganda with a high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) cases. Objective: To determine the treatment outcomes of TB retreatment cases and factors influencing these outcomes. Design: A retrospective cohort study of routinely collected National Tuberculosis Programme data between 1 January 2009 and 31 December 2010. Results: The study included 331 retreatment patients (68% males), with a median age of 36 years, 93 (28%) of whom were relapse smear-positive, 21 (6%) treatment after failure, 159 (48%) return after loss to follow-up, 26 (8%) relapse smear-negative and 32 (10%) relapse cases with no smear performed. Treatment success rates for all categories of retreatment cases ranged between 28% and 54%. Relapse smear-positive (P = 0.002) and treatment after failure (P = 0.038) cases were less likely to have a successful treatment outcome. Only 32% of the retreatment cases received a Category II treatment regimen; there was no difference in treatment success among patients who received Category II or Category I treatment regimens (P = 0.73). Conclusion: Management of TB retreatment cases and treatment success for all categories in three referral hospitals in Uganda was poor. Relapse smear-positive or treatment after failure cases were less likely to have a successful treatment outcome. PMID:26393019

  9. Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients

    PubMed Central

    Lee, Meng-Rui; Tsai, Chia-Jung; Wang, Wei-Jie; Chuang, Tzu-Yi; Yang, Chih-Mann; Chang, Lih-Yu; Lin, Ching-Kai; Wang, Jann-Yuan; Shu, Chin-Chong; Lee, Li-Na; Yu, Chong-Jen

    2015-01-01

    Abstract Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Outcome was defined as persistent culture positivity at 2 months into treatment. Of 167 enrolled patients, 26 had persistent culture positivity. RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential biomarkers. For predicting persistent culture positivity, receiver-operating characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624–0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512–0.713]) had good discriminative ability. Using a logistic regression model, low initial RANTES level (<440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (>3000 pg/mL) were associated with persistent culture positivity. Low initial RANTES level and initial smear positivity had a positive predictive value of 60% (12/20) for persistent culture positivity, compared with 4% (3/75) among patients with high RANTES level and smear negativity upon diagnosis. In the 72 patients with either low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2-month MMP-8 level had a positive and negative predictive value of 24 and 94%, respectively, for 2-month culture status. Aside from an initial sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment may be used to stratify risk for culture persistence. PMID:26426648

  10. Integration of Antiretroviral Therapy with Tuberculosis Treatment

    PubMed Central

    Abdool Karim, Salim S.; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L.; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M.; Friedland, Gerald; Abdool Karim, Quarraisha

    2011-01-01

    Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here. Results Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006). Conclusions The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher. PMID:22010915

  11. 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

  12. Prediction of 'highly skin smear positive' cases among MB leprosy patients using clinical parameters.

    PubMed

    Lemaster, J W; Shwe, T; Butlin, C R; Roche, P W

    2001-03-01

    Although 'highly skin smear positive' MB leprosy cases are known to be at high risk of relapse after release from treatment, and have been recommended to receive 'prolonged duration' MDT, government field-based control programmes without skin smear facilities have no simple alternative method to detect such cases. This study reports a significant prevalence of 'highly smear positive' cases amongst 2374 new multibacillary cases recently surveyed by skin smears in Nepal, and retrospectively analyses 555 newly detected, previously untreated BL and LL cases to identify clinical and laboratory parameters that may be associated with a 'highly positive skin smear'. While some parameters showed high sensitivity in predicting 'highly positive smear' status, none showed both high sensitivity and high specificity simultaneously. PMID:11355514

  13. 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

  14. Risk factors for tuberculosis treatment failure among pulmonary tuberculosis patients in four health regions of Burkina Faso, 2009: case control study

    PubMed Central

    Sawadogo, Bernard; Tint, Khin San; Tshimanga, Mufuta; Kuonza, Lazarus; Ouedraogo, Laurent

    2015-01-01

    Introduction In Burkina Faso, the tuberculosis (TB) treatment failure rate increased from 2.5% in 2000 to 8.3% in 2006. The risk factors for TB treatment failure in the country are not well known. The study aims to determine the risk factors for treatment failure among pulmonary tuberculosis patients in four health region of Burkina Faso and to recommend appropriate interventions. Methods A case control study was conducted among pulmonary TB patients who began TB treatment in 2009. A case was any patient who remained smear-positive at fifth month of TB treatment and a control was a patient who tested smear-negative at fifth month of treatment. A structured questionnaire was administered to one hundred cases and one hundred controls to collect information on exposure factors. Odds ratio were calculated using bivariate and multivariate analysis to determine the association between exposures and outcome. Results Multivariate analysis showed that independent risk factors for TB treatment failure were fail to take TB drugs for more than 14 consecutive days (OR = 18.53; 95% CI:4.56 - 75.22), sputum smear-positive at two months of treatment (OR = 11.52; 95%CI:5.18-25.60), existence of comorbidity (OR = 5.74; 95%CI:1.69-19.44), and use of traditional medicines or herbs (OR = 2.97; 95%CI:1.12-7.85). Conclusion Early identification of patients with the above risk factors for intense case management will improve TB treatment outcome. Patient with smear positive at 2ndnd month of treatment require more intense follow-up, and involving traditional healers who provide traditional medicines or herbs in the educational programme on TB are required. The national referral laboratory capacity needs to be strengthened to do drug susceptibility testing and routine drug monitoring on cases of non conversion at 2nd month of treatment. PMID:26327989

  15. 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

    2016-02-01

    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. PMID:27180737

  16. Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis

    PubMed Central

    Chung, Kuei-Pin; Chen, Jung-Yueh; Lee, Chih-Hsin; Wu, Huey-Dong; Wang, Jann-Yuan; Lee, Li-Na; Yu, Chong-Jen; Yang, Pan-Chyr

    2011-01-01

    OBJECTIVES: The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment. INTRODUCTION: Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied. METHODS: A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function. RESULTS: The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment. CONCLUSIONS: After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment. PMID:21655745

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. Assessment of treatment response in tuberculosis.

    PubMed

    Rockwood, Neesha; du Bruyn, Elsa; Morris, Thomas; Wilkinson, Robert J

    2016-06-01

    Antibiotic treatment of tuberculosis has a duration of several months. There is significant variability of the host immune response and the pharmacokinetic-pharmacodynamic properties of Mycobacterium tuberculosis sub-populations at the site of disease. A limitation of sputum-based measures of treatment response may be sub-optimal detection and monitoring of Mycobacterium tuberculosis sub-populations. Potential biomarkers and surrogate endpoints should be benchmarked against hard clinical outcomes (failure/relapse/death) and may need tailoring to specific patient populations. Here, we assess the evidence supporting currently utilized and future potential host and pathogen-based models and biomarkers for monitoring treatment response in active and latent tuberculosis. Biomarkers for monitoring treatment response in extrapulmonary, pediatric and drug resistant tuberculosis are research priorities. PMID:27030924

  3. Complication of antiquated tuberculosis treatment.

    PubMed

    Husta, Bryan; Devarajan, Sunjay; Reichner, Cristina A

    2014-01-01

    In the early 20th century, the rapid spread of tuberculosis (TB) invited novel therapies for treatment. A surgical procedure known as plombage was one such method where lobes were forced to collapse by placing an inert object such as mineral oil, paraffin wax, gauze or Lucite (methyl methacylate) balls. The collapse would lead to isolation of TB infection and decrease aeration of the affected lung. Removal of these objects had initially been, usually after 24 months, however this fell out of favor after the patient had recovered without commonly seen late complications. Decades later, reports have been made illustrating complications such as migration and infection of the plombe as well as expanding oleothorax. PMID:26029549

  4. Prediction of delayed treatment response in pulmonary tuberculosis: use of time to positivity values of Bactec cultures.

    PubMed

    Carroll, N M; Uys, P; Hesseling, A; Lawrence, K; Pheiffer, C; Salker, F; Duncan, K; Beyers, N; van Helden, P D

    2008-11-01

    New drugs that can shorten tuberculosis (TB) treatment and target drug resistant strains are urgently needed. A test which could predict patients at risk of a delayed response to treatment would facilitate clinical trials of new anti-tuberculosis drugs. A widely-used test for the assessment of response to treatment is sputum smear examination. Patients who are smear positive after 2 and 3 months of treatment are said to have delayed and significantly delayed treatment responses respectively. Time to positivity (TTP) values of Bactec cultures, from the first 2 weeks of treatment were used to predict delayed and significantly delayed treatment responses in patients with first time pulmonary tuberculosis. Changes in TTP values early in treatment were transformed to a response ratio (r). Values of r that were less than a threshold value (r(c)) indicated patients who were at risk of having delayed or significantly delayed response to treatment. Accuracy of prediction was sensitive to the timing of sputum sampling and adherence to therapy in the first 2 weeks. Based on TTP data from the first 2 weeks of treatment, significantly delayed treatment response could be predicted with a sensitivity of 75% and a specificity of 62% while the positive (PPV) and negative predictive values (NPV) were 14% and 97% respectively. While the high NPV indicates that a large proportion of patients with a satisfactory response to treatment can be reliably identified, the low PPV value underlines the need to use TTP in conjunction with other markers of disease activity to predict unfavourable treatment response in tuberculosis treatment. PMID:18456556

  5. Tuberculosis treatment and drug regimens.

    PubMed

    Sotgiu, Giovanni; Centis, Rosella; D'ambrosio, Lia; Migliori, Giovanni Battista

    2015-05-01

    Tuberculosis is an airborne infectious disease treated with combination therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial for maintaining adequate blood drug level. The emergence and spread of drug-resistant Mycobacterium tuberculosis strains are mainly favored by the inadequate medical management of the patients. The therapeutic approach for drug-resistant tuberculosis is cumbersome, because of the poor, expensive, less-effective, and toxic alternatives to the first-line drugs. New antituberculosis drugs (bedaquiline and delamanid) have been recently approved by the health authorities, but they cannot represent the definitive solution to the clinical management of drug-resistant tuberculosis forms, particularly in intermediate economy settings where the prevalence of drug resistance is high (China, India, and former Soviet Union countries). New research and development activities are urgently needed. Public health policies are required to preserve the new and old therapeutic options. PMID:25573773

  6. [New drugs for treatment of tuberculosis].

    PubMed

    Schaberg, T

    2016-02-01

    New effective drugs for the treatment of tuberculosis (TB) are necessary for two main reasons: firstly, it would be desirable to reduce the duration of TB treatment from 6 to 4 months and secondly, new drugs are urgently needed for the treatment of multidrug-resistant strains of Mycobacterium tuberculosis. For the first time since 1960 the two new drugs bedaquiline and delamanid were approved and licensed in 2014 for the treatment of multidrug-resistant M. tuberculosis; however, efforts to reduce the duration of treatment to 4 months using fluoroquinolones have not been successful. Further new drugs are currently in phase 2 and phase 3 studies; therefore, new treatment options can be expected within the next few years. PMID:26787496

  7. 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

  8. 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

  9. 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. PMID:26653188

  10. [Smoking and adherence to anti-tuberculosis treatment].

    PubMed

    Underner, M; Perriot, J; Peiffer, G; Meurice, J-C; Dautzenberg, B

    2016-02-01

    Smoking and tuberculosis are two major public health issues. Tobacco smoke increases the risk of Mycobacterium tuberculosis infection and the severity of pulmonary tuberculosis. Active smoking increases the risk of relapse of pulmonary and extra-pulmonary tuberculosis after treatment; smokers are less adherent to anti-tuberculosis treatment. Smoking cessation represent a means of controlling the tuberculosis epidemic in developing countries. This general review identified 17 studies in the international literature on the link between active smoking and the adherence to anti-tuberculosis treatment. It highlights a positive association between smoking and a lack of adherence to anti-tuberculosis treatment. This justifies the systematic application of aid to stopping smoking in smokers with tuberculosis. PMID:26777112

  11. [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

  12. Normalization of mediastinal widening after successful treatment of mediastinal tuberculosis.

    PubMed

    Raskin, Jo; Van Bleyenbergh, Pascal

    2016-08-01

    Clinical image of an asymmetrical mediastinal widening due to tuberculosis of mediastinal lymph nodes, without evidence of pulmonary tuberculosis. Image at first presentation and after successful treatment, showing normalization of the mediastinum. PMID:27149681

  13. [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

  14. Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection.

    PubMed

    Rangaka, Molebogeng X; Cavalcante, Solange C; Marais, Ben J; Thim, Sok; Martinson, Neil A; Swaminathan, Soumya; Chaisson, Richard E

    2015-12-01

    The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a crucial opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programmes focusing on single strategies rather than comprehensive programmes that deliver an integrated arsenal for tuberculosis control might continue to struggle. Tuberculosis preventive therapy is a poorly used method that is essential for controlling the reservoirs of disease that drive the epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission, and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. In this Series paper we outline challenges to implementation of preventive therapy and provide pragmatic suggestions for overcoming them. We further advocate for tuberculosis preventive therapy as the core of a renewed worldwide focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems and community engagement, and enhance sustainable large scale implementation of preventive therapy programmes. PMID:26515679

  15. 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

  16. 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

  17. Multi- and extensively drug-resistant tuberculosis in Latvia: trends, characteristics and treatment outcomes

    PubMed Central

    Riekstina, V.; Leimane, V.; Ozere, I.; Skenders, G.; Van den Bergh, R.; Kremer, K.; Acosta, C. D.; Harries, A. D.

    2014-01-01

    Setting: Drug-resistant tuberculosis (TB) is an important public health problem in Latvia. Objective: To document trends, characteristics and treatment outcomes of registered patients with multi-drug-resistant (MDR-) and extensively drug-resistant (XDR-) TB in Latvia from 2000 to 2010. Design: A retrospective national cohort study. Results: Of 1779 patients, 1646 (92%) had MDR- and 133 (8%) XDR-TB. Over 11 years, the proportion of XDR-TB among MDR-TB patients increased from 2% to 18%. Compared to MDR-TB patients, those with XDR-TB were significantly more likely to have failed MDR-TB treatment (OR 8.4, 95%CI 4.3–16.2), have human immunodeficiency virus infection (OR 3.2, 95%CI 1.8–5.7), be illegal drug users (OR 5.7, 95%CI 2.6–11.6) or have had contact with MDR-TB patients (OR 1.9, 95%CI 1.3–2.8). Cure rates for XDR-TB were 50%. Compared with MDR-TB patients, those with XDR-TB had a higher risk of treatment failure (29% vs. 8%, respectively, P < 0.001). Unfavourable treatment outcomes were significantly associated with being male; having smear-positive disease; pulmonary cavities; failure, default or relapse after previous MDR-TB treatment; and a history of incarceration. Conclusion: More MDR-TB in Latvia is now also XDR-TB. This study identified several risk factors for XDR-TB and, for unfavourable treatment outcomes, highlighting the importance of early diagnosis and appropriate management of MDR-/XDR-TB. PMID:26393098

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. Treatment guidelines for latent tuberculosis infection.

    PubMed

    2014-01-01

    The treatment of latent tuberculosis infection (LTBI) has been established as valid for patients at high risk for developing active tuberculosis. Treatment of LTBI is also considered an important strategy for eliminating tuberculosis (TB) in Japan. In recent years, interferon-gamma release assays have come into widespread use; isoniazid (INH) preventive therapy for HIV patients has come to be recommended worldwide; and there have been increases in both types of biologics used in the treatment of immune diseases as well as the diseases susceptible to treatment. In light of the above facts, the Prevention Committee and the Treatment Committee of the Japanese Society for Tuberculosis have jointly drafted these guidelines. In determining subjects for LTBI treatment, the following must be considered: 1) risk of TB infection/ development; 2) infection diagnosis; 3) chest image diagnosis; 4) the impact of TB development; 5) the possible manifestation of side effects; and 6) the prospects of treatment completion. LTBI treatment is actively considered when relative risk is deemed 4 or higher, including risk factors such as the following: HIV/AIDS, organ transplants (immunosuppressant use), silicosis, dialysis due to chronic renal failure, recent TB infection (within 2 years), fibronodular shadows in chest radiographs (untreated old TB), the use of biologics, and large doses of corticosteroids. Although the risk is lower, the following risk factors require consideration of LTBI treatment when 2 or more of them are present: use of oral or inhaled corticosteroids, use of other immunosuppressants, diabetes, being underweight, smoking, gastrectomy, and so on. In principle, INH is administered for a period of 6 or 9 months. When INH cannot be used, rifampicin is administered for a period of 4 or 6 months. It is believed that there are no reasons to support long-term LTBI treatment for immunosuppressed patients in Japan, where the risk of infection is not considered markedly high

  6. Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis

    PubMed Central

    Mitnick, Carole D.; Shin, Sonya S.; Seung, Kwonjune J.; Rich, Michael L.; Atwood, Sidney S.; Furin, Jennifer J.; Fitzmaurice, Garrett M.; Alcantara Viru, Felix A.; Appleton, Sasha C.; Bayona, Jaime N.; Bonilla, Cesar A.; Chalco, Katiuska; Choi, Sharon; Franke, Molly F.; Fraser, Hamish S.F.; Guerra, Dalia; Hurtado, Rocio M.; Jazayeri, Darius; Joseph, Keith; Llaro, Karim; Mestanza, Lorena; Mukherjee, Joia S.; Muñoz, Maribel; Palacios, Eda; Sanchez, Epifanio; Sloutsky, Alexander; Becerra, Mercedes C.

    2009-01-01

    BACKGROUND Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [±SD] number of regimens, 4.2±1.9 vs. 3.2±1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4±1.1 vs. 5.3±1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3±1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis. PMID:18687637

  7. [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

  8. [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. PMID:7600599

  9. Adjunctive therapy of Mycobacterium vaccae vaccine in the treatment of multidrug-resistant tuberculosis: A systematic review and meta-analysis

    PubMed Central

    WENG, HONG; HUANG, JING-YU; MENG, XIANG-YU; LI, SHENG; ZHANG, GU-QIN

    2016-01-01

    A number of studies have suggested that the Mycobacterium vaccae (MV) vaccine as an adjunctive therapy has a positive effect in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, the result is inconclusive. The aim of the present study was to systematically evaluate the effect and safety of MV as an adjunctive therapy in the treatment of MDR-TB. A computerized search of PubMed, Embase, Cochrane Central Register of Controlled Trials, CBM, CNKI and VIP until October 2014 was conducted to collect the relevant studies. The main outcome measures were the sputum smear positive-turned-negative rate, the absorption rate of TB foci and the closure situation of the TB cavity. Two investigators identified the eligible studies and extracted data independently. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and pooled using the fixed effects model. A total of 25 studies involving 2,281 patients with MDR-TB were included. The pooled OR was 3.84 (95% CI, 3.84–4.73) for the sputum smear positive-turned-negative, 4.08 (95% CI, 3.08–5.45) for the absorption rate of TB foci, and 3.42 (95% CI, 2.68–4.37) for the closure situation of TB cavity. Therefore, MV has a significant effect as an adjunctive therapy in the treatment of MDR-TB. However, larger scale multicenter randomized controlled trials are required to confirm this evidence for limited latent bias at present. PMID:27123253

  10. Adherence to tuberculosis treatment among migrant pulmonary tuberculosis patients in Shandong, China: a quantitative survey study.

    PubMed

    Zhou, Chengchao; Chu, Jie; Liu, Jinan; Gai Tobe, Ruoyan; Gen, Hong; Wang, Xingzhou; Zheng, Wengui; Xu, Lingzhong

    2012-01-01

    Adherence to TB treatment is the most important requirement for efficient TB control. Migrant TB patients' "migratory" nature affects the adherence negatively, which presents an important barrier for National TB Control Program in China. Therefore, TB control among migrants is of high importance.The aim of this study is to describe adherence to TB treatment among migrant TB patients and to identify factors associated with adherence. A total of 12 counties/districts of Shandong Province, China were selected as study sites. 314 confirmed smear positive TB patients were enrolled between August 2(nd) 2008 and October 17(th) 2008, 16% of whom were non-adherent to TB therapy. Risk factors for non-adherence were: the divorced or bereft of spouse, patients not receiving TB-related health education before chemotherapy, weak incentives for treatment adherence, and self supervision on treatment. Based on the risk factors identified, measures are recommended such as implementing health education for all migrant patients before chemotherapy and encouraging primary care workers to supervise patients. PMID:23284993

  11. Did we reach the 2005 targets for tuberculosis control?

    PubMed

    Dye, Christopher; Hosseini, Mehran; Watt, Catherine

    2007-05-01

    The World Health Assembly set targets to detect by 2005 at least 70% of all new sputum smear-positive cases arising each year and to cure at least 85% of these cases. The national tuberculosis (TB) control programmes of 199 countries reported that in 2005, 2.3 million new smear-positive cases were diagnosed under WHOs DOTS strategy, out of an estimated 3.9 million (95% confidence limit (CL) 3.4 million to 4.4 million) new smear-positive cases arising in that year, a global case detection rate of 60% (95% CL 52% to 69%). Of 2.1 million new smear-positive patients registered for treatment in 2004, 84% had successful outcomes. Of the regions, only the WHO Western Pacific Region reached both targets, with case detection and treatment success rates of 76% and 91%, respectively; South-East Asia reached the treatment success target with a rate of 87%. In relation to countries, WHO estimates that 67 achieved the target detection rates and 57 achieved the target for treatment success, with 26 - including high-burden countries China, the Philippines and Viet Nam - achieving both targets. DOTS programmes diagnosed more than 26 million patients (all forms of TB) in 1995-2005. Building on this success, the Global Plan to Stop TB 2006-2015, describes the actions needed to implement WHOs new Stop TB Strategy over the coming decade to reduce TB incidence, prevalence and deaths in line with the Millennium Development Goals. PMID:17639221

  12. Treatment of Drug Susceptible Pulmonary Tuberculosis.

    PubMed

    Shin, Hong-Joon; Kwon, Yong-Soo

    2015-07-01

    Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs. PMID:26175767

  13. Current treatment options for latent tuberculosis infection.

    PubMed

    Bocchino, Marialuisa; Matarese, Alessandro; Sanduzzi, Alessandro

    2014-05-01

    Treatment of latent tuberculosis infection (LTBI) is a key component in TB control strategies worldwide. However, as people with LTBI are neither symptomatic nor contagious, any screening decision should be weighed carefully against the potential benefit of preventing active disease in those who are known to be at higher risk and are willing to accept therapy for LTBI. This means that a targeted approach is desirable to maximize cost effectiveness and to guarantee patient adherence. We focus on LTBI treatment strategies in patient populations at increased risk of developing active TB, including candidates for treatment with tumor necrosis factor-α blockers. In the last 40 years, isoniazid (INH) has represented the keystone of LTBI therapy across the world. Although INH remains the first therapeutic option, alternative treatments that are effective and associated with increased adherence and economic savings are available. Current recommendations, toxicity, compliance, and cost issues are discussed in detail in this review. A balanced relationship between the patient and healthcare provider could increase adherence, while cost-saving treatment strategies with higher effectiveness, fewer side effects, and of shorter duration should be offered as preferred. PMID:24789003

  14. Tuberculosis treatment and management--an update on treatment regimens, trials, new drugs, and adjunct therapies.

    PubMed

    Zumla, Alimuddin; Chakaya, Jeremiah; Centis, Rosella; D'Ambrosio, Lia; Mwaba, Peter; Bates, Matthew; Kapata, Nathan; Nyirenda, Thomas; Chanda, Duncan; Mfinanga, Sayoki; Hoelscher, Michael; Maeurer, Markus; Migliori, Giovanni Battista

    2015-03-01

    WHO estimates that 9 million people developed active tuberculosis in 2013 and 1·5 million people died from it. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis continue to spread worldwide with an estimated 480,000 new cases in 2013. Treatment success rates of MDR and XDR tuberculosis are still low and development of new, more effective tuberculosis drugs and adjunct therapies to improve treatment outcomes are urgently needed. Although standard therapy for drug-sensitive tuberculosis is highly effective, shorter, more effective treatment regimens are needed to reduce the burden of infectious cases. We review the latest WHO guidelines and global recommendations for treatment and management of drug-sensitive and drug-resistant tuberculosis, and provide an update on new drug development, results of several phase 2 and phase 3 tuberculosis treatment trials, and other emerging adjunct therapeutic options for MDR and XDR tuberculosis. The use of fluoroquinolone-containing (moxifloxacin and gatifloxacin) regimens have failed to shorten duration of therapy, and the new tuberculosis drug pipeline is sparse. Scale-up of existing interventions with increased investments into tuberculosis health services, development of new antituberculosis drugs, adjunct therapies and vaccines, coupled with visionary political leadership, are still our best chance to change the unacceptable status quo of the tuberculosis situation worldwide and the growing problem of drug-resistant tuberculosis. PMID:25773212

  15. 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

  16. 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

  17. HIV treatment cascade in tuberculosis patients

    PubMed Central

    Lessells, Richard J.; Swaminathan, Soumya; Godfrey-Faussett, Peter

    2015-01-01

    Purpose of review Globally, the number of deaths associated with tuberculosis (TB) and HIV coinfection remains unacceptably high. We review the evidence around the impact of strengthening the HIV treatment cascade in TB patients and explore recent findings about how best to deliver integrated TB/HIV services. Recent findings There is clear evidence that the timely provision of antiretroviral therapy (ART) reduces mortality in TB/HIV coinfected adults. Despite this, globally in 2013, only around a third of known HIV-positive TB cases were treated with ART. Although there is some recent evidence exploring the barriers to achieve high coverage of HIV testing and ART initiation in TB patients, our understanding of which factors are most important and how best to address these within different health systems remains incomplete. There are some examples of good practice in the delivery of integrated TB/HIV services to improve the HIV treatment cascade. However, evidence of the impact of such strategies is of relatively low quality for informing integrated TB/HIV programming more broadly. In most settings, there remain barriers to higher-level organizational and functional integration. Summary There remains a need for commitment to patient-centred integrated TB/HIV care in countries affected by the dual epidemic. There is a need for better quality evidence around how best to deliver integrated services to strengthen the HIV treatment cascade in TB patients, both at primary healthcare level and within community settings. PMID:26352390

  18. 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. PMID:21740653

  19. 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

  20. [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

  1. 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

  2. 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

  3. THE TREATMENT OF TUBERCULOSIS WITH CYANOCUPROL.

    PubMed

    Otani, M

    1916-08-01

    Cyanocuprol is markedly effective in tuberculosis, and we believe that it will play an important part in clinical medicine. It may be used more generally than tuberculin. The amount of the dose is closely related to the reaction and the final results. It should be determined for each patient after a careful examination of his symptoms. The maximum dose of 8.5 cc. should in no case be exceeded. The shortest interval between injections should be 2 weeks. If the drug is given after a shorter interval, no improvement is observed and the effects are sometimes dangerous. In order to obtain the best results the patient should be placed under conditions of complete physical and mental rest after the injection; this applies even to light cases. Care should also be taken to secure rest for the lesion. During the period of the treatment irritants to the lesion, such as potassium iodide or tuberculin, should be avoided; apricot juice, guaiacol and its derivatives, and iodol are contraindicated. No marked idiosyncrasy has been noted and no accumulative effects have been observed. PMID:19868034

  4. 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

  5. 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

    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 global

  6. Treatment Outcome of Tuberculosis Patients under Directly Observed Treatment Short Course and Factors Affecting Outcome in Southern Ethiopia: A Five-Year Retrospective Study.

    PubMed

    Gebrezgabiher, Gebremedhin; Romha, Gebremedhin; Ejeta, Eyasu; Asebe, Getahun; Zemene, Endalew; Ameni, Gobena

    2016-01-01

    Tuberculosis (TB) is one of the major public health and socio-economic issues in the 21st century globally. Assessment of TB treatment outcomes, and monitoring and evaluation of its risk factors in Directly Observed Treatment Short Course (DOTS) are among the major indicators of the performance of a national TB control program. Hence, this institution-based retrospective study was conducted to determine the treatment outcome of TB patients and investigate factors associated with unsuccessful outcome at Dilla University Referral Hospital, southern Ethiopia. Five years (2008 to 2013) TB record of TB clinic of the hospital was reviewed. A total 1537 registered TB patients with complete information were included. Of these, 942 (61.3%) were male, 1015 (66%) were from rural areas, 544 (35.4%) were smear positive pulmonary TB (PTB+), 816 (53.1%) were smear negative pulmonary TB (PTB-) and 177(11.5%) were extra pulmonary TB (EPTB) patients. Records of the 1537 TB patients showed that 181 (11.8%) were cured, 1129(73.5%) completed treatment, 171 (11.1%) defaulted, 52 (3.4%) died and 4 (0.3%) had treatment failure. The overall mean treatment success rate of the TB patients was 85.2%. The treatment success rate of the TB patients increased from 80.5% in September 2008-August 2009 to 84.8% in September 2012-May 2013. Tuberculosis type, age, residence and year of treatment were significantly associated with unsuccessful treatment outcome. The risk of unsuccessful outcome was significantly higher among TB patients from rural areas (AOR = 1.63, 95% CI: 1.21-2.20) compared to their urban counterparts. Unsuccessful treatment outcome was also observed in PTB- patients (AOR = 1.77, 95% CI: 1.26-2.50) and EPTB (AOR = 2.07, 95% CI: 1.28-3.37) compared to the PTB+ patients. In conclusion, it appears that DOTS have improved treatment success in the hospital during five years. Regular follow-up of patients with poor treatment outcome and provision of health information on TB treatment to

  7. 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 ...

  8. 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 ...

  9. 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

  10. 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

  11. 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

  12. 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 ...

  13. Surgical Treatment of Spinal Tuberculosis Complicated with Extensive ABSCESS

    PubMed Central

    Brito, Joaquim Soares Do; Tirado, António; Fernandes, Pedro

    2014-01-01

    Purpose Tuberculosis can be responsible for extensive spinal lesions. Despite the efficacy of medical treatment, surgery is indicated to avoid or correct significant deformity, treat spinal instability, prevent neurological compromise, and to eradicate an extensive tuberculous abscess. In this paper we present our experience in the surgical management of spinal tuberculosis complicated with large abscess. Patients and Methods Fifteen patients with spinal tuberculosis complicated with extensive abscess were identified; and nine of those patients had extension of the infection into the epidural space. The average age at treatment was 34 years old. Seven patients had thoracic infection, seven patients had lumbar infection and one had thoracolumbar infection. Six patients had neurological deficit at presentation. All patients were surgically treated with abscess debridement, spinal stabilization and concurrent antituberculous chemotherapy. A single anterior surgical approach was used in three cases, a posterior approach was used in four others and a combined approach was performed in eight patients. Results Surgical management allowed for effective abscess debridement and sspinal stabilization in this cohort. In combination with antituberculous drugs, surgical treatment resulted in infection eradication and bone fusion in all patients at 24 month average follow-up. Satisfactory neurological outcomes with improved American Spinal Injury Association (ASIA) scores were observed in 100% of patients. Conclusion Surgical treatment for spinal tuberculosis abscess can lead to satisfactory clinical outcomes. PMID:25328472

  14. 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

  15. 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

  16. A review of emerging trends in the treatment of tuberculosis.

    PubMed

    Kaur, Manpreet; Garg, Tarun; Narang, R K

    2016-01-01

    This review attempts to summarize the information available on emerging trends in the treatment of tuberculosis caused by the bacteria Mycobacterium tuberculosis. Nanostructured biomaterials, liposomes, microparticles and solid lipid nanoparticles have unique physicochemical properties such as particularly small and convenient size, sustained release, great surface area to mass ratio and high reactivity with structure. These properties can be useful in easing the administration of antimicrobial drugs, thereby reducing the number of limitations in long-established antimicrobial therapeutics. In recent years, the encapsulation of antimicrobial drugs in all carrier systems has emerged as an innovative and promising change that increases therapeutic efficiency and reduces undesirable side effects of the drugs. PMID:25365354

  17. Role of vitamin A supplementation in the treatment of tuberculosis.

    PubMed

    Mathur, Murli L

    2007-01-01

    Vitamin A deficiency has been commonly observed in patients with tuberculosis. Low serum retinol levels return to normal after antituberculosis treatment even when no supplements are provided. The deficiency of vitamin A observed in patients with tuberculosis might have contributed to the development of tuberculous disease in them. Alternatively, deficiency could be the result of loss of appetite, poor intestinal absorption, increased urinary loss of vitamin A or acute phase reaction in TB. Vitamin A deficiency lowers immunity while vitamin A supplementation reduces morbidity and mortality, particularly from measles and diarrhoea. Vitamin A supplementation also decreases the mortality rate in HIV-infected children and delays the progression of HIV disease in infected subjects. A higher incidence of lung cancer and increased mortality have been observed in smokers after beta-carotene supplementation. Zinc deficiency is also common in tuberculosis, which may impose a secondary vitamin A deficiency. Clinical trials have shown conflicting results regarding the effect of supplementation of vitamin A, alone or with other micronutrients, on time taken to sputum conversion in patients with pulmonary tuberculosis. Supplementation with multiple micronutrients (including zinc) rather than vitamin A alone may be more beneficial in patients with tuberculosis, but clinical trials on such a combination are lacking. PMID:17557517

  18. Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment

    PubMed Central

    Cliff, Jacqueline M.; Cho, Jang-Eun; Lee, Ji-Sook; Ronacher, Katharina; King, Elizabeth C.; van Helden, Paul; Walzl, Gerhard; Dockrell, Hazel M.

    2016-01-01

    Background. Currently, there are no tools to accurately predict tuberculosis relapse. This study aimed to determine whether patients who experience tuberculosis relapse have different immune responses to mycobacteria in vitro than patients who remain cured for 2 years. Methods. Patients with an initial episode of pulmonary tuberculosis were recruited in South Africa. Diluted blood, collected at diagnosis and after 2 and 4 weeks of treatment, was cultured with live Mycobacterium tuberculosis for 6 days, and cellular RNA was frozen. Gene expression in samples from 10 patients who subsequently experienced relapse, confirmed by strain genotyping, was compared to that in samples from patients who remained cured, using microarrays. Results. At diagnosis, expression of 668 genes was significantly different in samples from patients who experienced relapse, compared with expression in patients who remained successfully cured; these differences persisted for at least 4 weeks. Gene ontology and biological pathways analyses revealed significant upregulation of genes involved in cytotoxic cell-mediated killing. Results were confirmed by real-time quantitative reverse-transcription polymerase chain reaction analysis in a wider patient cohort. Conclusions. These data show that patients who will subsequently experience relapse exhibit altered immune responses, including excessively robust cytolytic responses to M. tuberculosis in vitro, at the time of diagnosis, compared with patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited in drug development. PMID:26351358

  19. Profile of tuberculosis patients with delayed sputum smear conversion in the Pacific island of Vanuatu

    PubMed Central

    Viney, K.; Tarivonda, L.; Roseveare, C.; Tagaro, M.; Marais, B. J.

    2014-01-01

    Setting: National tuberculosis control programme, Vanuatu. Objective: To assess tuberculosis (TB) trends, characterise sputum smear-positive patients with non-conversion at 2 months and assess their treatment outcomes. Design: Evaluation of programme data over a 9-year period (2004–2012), comparing 2-month sputum non-converters (delayed converters) with sputum smear converters diagnosed in 2011 and 2012. Results: Annual TB case numbers were similar over the study period, with an average TB notification rate of 58 per 100 000 population. Of 417 sputum smear-positive cases, 74 (18%) were delayed converters. Delayed converters were more likely than converters (88% vs. 79%) to have had high pre-treatment sputum smear grades (OR 2.5, 95%CI 0.97–6.45). Among delayed converters, treatment adherence was high (99% good adherence), outcomes were generally good (90% treatment success, 85% cure, 4% treatment failure) and no drug resistance was detected. Deaths were unexpectedly common among converters (11/80, 14%), with significantly more deaths in Tafea than in Shefa Province (7/58 vs. 2/80, OR 5.35, 95%CI 1.07–26.79). Tafea Province also had the greatest number of delayed converters (30/74, 40.5%) and the highest TB incidence rate. Conclusion: Delayed sputum conversion was relatively uncommon, and was not associated with adverse outcomes or drug resistance. Regional differences require further investigation to better understand local factors that may compromise patient management. PMID:26477281

  20. 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

  1. 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

  2. Multidrug-resistant tuberculosis treatment with linezolid-containing regimen

    PubMed Central

    Farshidpour, Maham; Ebrahimi, Golnaz; Mirsaeidi, Mehdi

    2014-01-01

    The following is a case of multidrug-resistant pulmonary tuberculosis (MDR-TB) that was treated successfully with a linezolid-containing regimen. It was found that linezolid is an efficient medicine for MDR-TB treatment with an acceptable side effect profile. Treatment was maintained for 18 months, and closely monitoring toxicities did not reveal evidence of any neurologic adverse effects. However, despite our expectation, thrombocytopenia was seen after 2 years follow-up. PMID:25110635

  3. [Tuberculosis infection control - recommendations of the DZK].

    PubMed

    Ziegler, R; Just, H-M; Castell, S; Diel, R; Gastmeier, P; Haas, W; Hauer, B; Loytved, G; Mielke, M; Moser, I; Nienhaus, A; Richter, E; Rüden, H; Rüsch-Gerdes, S; Schaberg, T; Wischnewski, N; Loddenkemper, R

    2012-06-01

    The epidemiological situation of tuberculosis (TB) in Germany has improved considerably during the past few years. However, those in unprotected contact with infectious tuberculosis patients frequently and/or over longer periods of time and/or intensively continue to have a higher risk for TB infection. Rapid diagnosis, prompt initiation of effective treatment, and adequate infection control measures are of particular importance to prevent infection. The present recommendations depict the essentials of infection control as well as specific measures in the hospital (isolation, criteria for its duration and technical requirements, types of respiratory protection, disinfection measures, waste disposal). The specific requirements for outpatients (medical practice), at home, for ambulance services, and in congregate settings, including prisons, are also addressed. Compared with the previous recommendations the pattern of respiratory protection measures has been simplified. As a rule, hospital staff and those visiting infectious tuberculosis patients are advised to wear respiratory protection that satisfies the criteria of FFP2-masks (DIN EN 149), while patients should wear mouth-nose protectors (surgical masks) in the presence of others and outside the isolation room. A detailed depiction of criteria for isolation and its duration in smear positive and only culturally confirmed pulmonary tuberculosis has been added. PMID:22723258

  4. Tuberculosis case notification data in Viet Nam, 2007 to 2012

    PubMed Central

    Nhung, Nguyen Viet; Khanh, Pham Huyen; Hennig, Cornelia

    2015-01-01

    Tuberculosis (TB) remains a major cause of morbidity and mortality, and Viet Nam ranks 12 among the 22 high-TB burden countries. This study analyses surveillance data of the National Tuberculosis Control Programme in Viet Nam for the six-year period 2007 to 2012. During the study period, 598 877 TB cases (all forms) were notified, and 313 225 (52.3%) were new smear-positive cases. The case notification rate of new smear-positive cases was decreased, from 65 per 100 000 population in 2007 to 57 per 100 000 population in 2012; this decrease was observed for males and females in all age groups except males aged 0–14 and females aged 15–24 years. The male-to-female ratio of new smear-positive TB cases increased from 2.85 in 2007 to 3.02 in 2012. The average annual cure rate of new smear-positive cases was 90.3%. The high male-to-female ratio for new smear-positive TB cases in this notification data was lower than that from the 2007 TB prevalence survey in Viet Nam, suggesting a lower case detection for males. The decrease in new smear-positive case notification rates may reflect a decline in TB incidence in Viet Nam as several programmatic improvements have been made, although further research is required to increase case detection among young males and children. PMID:25960918

  5. 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

  6. 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...

  7. Diagnosis & treatment of tuberculosis in HIV co-infected patients

    PubMed Central

    Padmapriyadarsini, C.; Narendran, G.; Swaminathan, Soumya

    2011-01-01

    Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection. PMID:22310818

  8. Accessibility to tuberculosis treatment: assessment of health service performance.

    PubMed

    Arakawa, Tiemi; Arcêncio, Ricardo Alexandre; Scatolin, Beatriz Estuque; Scatena, Lúcia Marina; Ruffino-Netto, Antônio; Villa, Tereza Cristina Scatena

    2011-01-01

    The aim of this study was to assess the accessibility of patients to the treatment of tuberculosis in Ribeirão Preto, countryside of São Paulo State. Evaluation study type, with a quantity approach. Interviews with 100 patients initiated on anti-tuberculosis chemotherapy between 2006-2007 were conducted, using a structured questionnaire based on the Primary Care Assessment Tool (PCAT). Data were analyzed through variance analysis. There was a positive feedback regarding to organizational accessibility, however, the performance of health services has been unsatisfactory in providing transportation vouchers and in addressing the need to use transport for displacement to the health unit, resulting in indirect costs to patients. The services with the highest number of patients treated were those with higher irregularity in the conduct of home visits, showing that the availability of resources (human, material and time) and the organization of care may influence the accessibility to treatment. PMID:21876953

  9. 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

  10. Bedaquiline for the treatment of drug-resistant tuberculosis.

    PubMed

    Bélard, Sabine; Heuvelings, Charlotte C; Janssen, Saskia; Grobusch, Martin P

    2015-05-01

    Bedaquiline is a much-needed novel drug which is highly effective against drug-resistant tuberculosis. While its clinical development has been laudably fast-tracked and the drug is now available for inclusion into treatment regimens when no suitable alternatives exist, clinical experience with bedaquiline is still limited. Phase III trial data and Phase IV studies are needed particularly to study different patient populations and to optimize treatment regimens. Drug resistance to bedaquiline needs to be monitored carefully, and full access to bedaquiline treatment where it is appropriate and needed must be promoted. PMID:25797824

  11. 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

  12. 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

  13. Multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis

    PubMed Central

    van der Werf, Marieke J.; Langendam, Miranda W.; Huitric, Emma; Manissero, Davide

    2012-01-01

    We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0–141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles. PMID:22005918

  14. 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

  15. A cross-sectional and follow-up study of leukopenia in tuberculosis patients: prevalence, risk factors and impact of anti-tuberculosis treatment

    PubMed Central

    Lin, Fei-Shen; Wu, Mei-Ying; Tu, Wen-Jun; Pan, Hong-Qiu; Zheng, Jian; Shi, Jun-Wei; Fei, Zhong-Ting; Zhang, Rui-Mei; Yan, Wei-Guo; Shang, Ming-Qun; Zheng, Qiang; Wang, Meng-Jie

    2015-01-01

    Background To investigate the prevalence of and risk factors for leukopenia in tuberculosis patients and the impact of anti-tuberculosis regimens on the occurrence of leukopenia in newly treated tuberculosis patients. Methods A total of 1,904 tuberculosis patients were included in the study. A cross-sectional survey of the prevalence of leukopenia was initially conducted, and then factors influencing leukopenia were identified using Logistic regression analysis. Non-treatment factors influencing peripheral blood leukocyte counts were analyzed using univariate COX proportional hazards models. Covariate analysis was used to assess the independent effect of different anti-tuberculosis regimens on peripheral blood leukocyte counts. Results Being female, advanced age and longer duration of previous anti-tuberculosis treatment (>6 month) were risk factors for leukopenia in tuberculosis patients, while secondary pulmonary tuberculosis, higher body mass index (BMI: 24−27.9 kg/m2), and higher degree of education (senior high school or above) were protective factors. Gender, vegetable consumption, drinking, pulmonary infection, other chronic diseases, and use of antibiotics were significantly associated with the development of leukopenia in patients on anti-tuberculosis treatment. In tuberculosis patients treated with anti-tuberculosis regimens not containing antibiotics, peripheral blood leukocyte levels gradually declined with the prolongation of treatment duration. In tuberculosis patients treated with anti-tuberculosis regimens containing antibiotics, peripheral blood leukocyte levels showed a declining trend. Conclusions Female patients, patients at advanced age and recurrent tuberculosis patients having longer previous anti-tuberculosis treatment are high-risk populations for leukopenia. Attention should be paid to the influence of vegetable consumption and drinking, co-morbidities and use of antibiotics during anti-tuberculosis treatment. PMID:26793345

  16. Treatment of tuberculosis in Turkey in terms of medical ethics.

    PubMed

    Demir, Müge; Örnek Büken, Nüket

    2015-09-01

    Having a history as old as the history of humanity, Tuberculosis (TB) is a serious disease and it is regarded as an important a public health problem not only for its medical aspect but also for its social and ethical aspects. As a result of the discovery of the cure for TB and the improvement of humans' living conditions, the TB problem was believed to be solved and a relaxation in the battle against TB was observed around the world by 1980s. World Health Organization (WHO) declared a state of emergency for the battle against TB in 1993. According to the "Global Tuberculosis Control 2014" which was published by WHO, TB remains one of the world's deadliest communicable diseases. This article argues that tuberculosis is one of the most important neglected topics in medical ethics as regards individual obligations to avoid infecting others, coercive social distancing measures, third-party notification, health workers' duty to treat contagious patients, and justice.The purpose of this article is provide a picture of the current situation of TB treatment in Turkey in terms of medical ethics. PMID:26523903

  17. Rapid genotypic detection of rifampin- and isoniazid-resistant Mycobacterium tuberculosis directly in clinical specimens.

    PubMed

    Bang, Didi; Bengård Andersen, Ase; Thomsen, Vibeke Østergaard

    2006-07-01

    A multiplex PCR DNA strip assay (Genotype MTBDR) designed to detect rifampin (rpoB) and high-level isoniazid (katG) resistance mutations in Mycobacterium tuberculosis isolates was optimized for clinical specimens. Successful genotypic results were achieved with 36 of 38 (95%) smear-positive respiratory specimens, allowing rapid therapeutic adjustments in transmittable drug-resistant tuberculosis. PMID:16825393

  18. 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

  19. Treatment Experiences and Management Outcomes for Skipped Multisegmental Spinal Tuberculosis.

    PubMed

    Mei, Gang; Luo, Fei; Zhang, Zehua; Dai, Fei; Zhou, Qiang; He, Qingyi; Hou, Tianyong; Xu, Jianzhong

    2016-01-01

    China ranks second among the 22 countries with the highest burden of tuberculosis. The goals of this study were to evaluate the clinical outcomes of treatment of skipped multisegmental spinal tuberculosis and to investigate the selection strategy for the optimal procedure based on focal characteristics. From March 1999 to December 2013, 24 patients with skipped multisegmental spinal tuberculosis were enrolled in this study. Ten patients underwent an anterior procedure (anterior group). Four patients underwent a combined anterior and posterior procedure (combined anterior and posterior group). Ten patients underwent a posterior procedure (posterior group). All patients were evaluated according to clinical presentation and radiographic, computed tomography, and magnetic resonance imaging findings. The focal tissues of all patients underwent drug susceptibility testing. The patients underwent clinical and radiologic follow-up an average of 18.6 months post-operatively. The cohort included 13 male and 11 female patients (age range, 15-69 years). The patients showed significant improvement in deformity and neurologic deficits. All patients had graft union 6 to 12 months postoperatively. No patient had surgical complications. Postoperative recurrence occurred in 1 patient in the combined anterior and posterior group. Two patients had strains that were resistant to at least 1 anti-tuberculosis drug. One patient had multidrug-resistant strains. All 24 patients had achieved cure at final follow-up. This study showed that the 3 procedures can safely and effectively achieve nerve decompression, graft fusion, and kyphosis correction. The procedure should be chosen according to the patient's general condition, focal characteristics, and type of complication, and the surgeon's experience. PMID:26709565

  20. 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

  1. 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

  2. The Italian AIPO study on tuberculosis treatment results, report 1995. National AIPO "Tuberculosis" Study Group.

    PubMed

    Ambrosetti, M; Besozzi, G; Codecasa, L R; Farris, B; Nutini, S; Saini, L; Casali, L; Nardini, S; Migliori, G B

    1999-02-01

    In Italy, no national data on tuberculosis (TB) treatment results were available. In 1995, the AIPO (Italian Association of Hospital Pneumologists) TB Study Group, in collaboration with the Istituto Superiore di Sanità (technical branch of the Ministry of Health), started a prospective monitoring activity based on World Health Organization (WHO) and International Union against Tuberculosis and Lung Disease (IUATLD) recommendations. Data were collected from a nationwide network of 41 TB units, managing a significant proportion of all TB cases notified in Italy each year. The aim of this study was to analyse the case findings and treatment results for the year 1995. Seven hundred and seventy eight TB cases were reported (59% males; 21% immigrants), 640 (82%) being new cases. Of these cases, 517 (66%) were pulmonary, 239 (31%) extrapulmonary and 22 (3%) both pulmonary and extrapulmonary. The main risk factors for TB were a history of recent contact and alcohol abuse among native Italians and human immunodeficiency virus-seropositive status among immigrants. The majority of immigrants were from Africa and South America, and had been in Italy > 24 months before diagnosis of TB. Thirty-seven per cent of patients had a positive direct sputum smear examination for alcohol acid-fast bacilli; 20% were resistant to any drug (monoresistance to isoniazid 3.5%; multidrug resistance 5.2%). In 95% of cases, the duration of treatment was < 12 months. The overall success rate (cured plus treatment completed) was 81.1%. A significantly higher percentage of deaths was found in native Italians (being age-related), whereas immigrants had a higher default rate. PMID:10218371

  3. Attitudes towards preventive tuberculosis treatment among hospital staff.

    PubMed

    Pathak, Vidya; Harrington, Zinta; Dobler, Claudia C

    2016-01-01

    Background. Healthcare workers have an increased risk of latent tuberculosis infection (LTBI), but previous studies suggested that they might be reluctant to accept preventive tuberculosis (TB) treatment. We aimed to examine doctors' and nurses' experience of TB screening and to explore their attitudes towards preventive TB treatment. Methods. We conducted a survey among randomly selected healthcare workers at a tertiary hospital in Sydney, Australia, using a paper-based questionnaire. Results. A total of 1,304 questionnaires were distributed and 311 (24%) responses were received. The majority of hospital staff supported preventive TB treatment in health care workers with evidence of latent TB infection (LTBI) in general (74%, 164/223) and for them personally (81%, 198/244) while 80 and 53 healthcare workers respectively had no opinion on the topic. Staff working in respiratory medicine were significantly less likely to support preventive TB treatment in health care workers in general or for them personally if they would have evidence of LTBI compared to other specialties (p = 0.001). Only 13% (14/106) of respondents with evidence of LTBI indicated that they had been offered preventive TB treatment. Twenty-one percent (64/306) of respondents indicated that they did not know the difference between active and latent TB. Among staff who had undergone testing for LTBI, only 33% (75/230) felt adequately informed about the meaning of their test results. Discussion. Hospital staff in general had positive attitudes towards preventive TB treatment, but actual treatment rates were low and perceived knowledge about LTBI was insufficient among a significant proportion of staff. The gap between high support for preventive TB treatment among staff and low treatment rates needs to be addressed. Better education on the concept of LTBI and the meaning of screening test results is required. PMID:26966667

  4. Attitudes towards preventive tuberculosis treatment among hospital staff

    PubMed Central

    Pathak, Vidya; Harrington, Zinta

    2016-01-01

    Background. Healthcare workers have an increased risk of latent tuberculosis infection (LTBI), but previous studies suggested that they might be reluctant to accept preventive tuberculosis (TB) treatment. We aimed to examine doctors’ and nurses’ experience of TB screening and to explore their attitudes towards preventive TB treatment. Methods. We conducted a survey among randomly selected healthcare workers at a tertiary hospital in Sydney, Australia, using a paper-based questionnaire. Results. A total of 1,304 questionnaires were distributed and 311 (24%) responses were received. The majority of hospital staff supported preventive TB treatment in health care workers with evidence of latent TB infection (LTBI) in general (74%, 164/223) and for them personally (81%, 198/244) while 80 and 53 healthcare workers respectively had no opinion on the topic. Staff working in respiratory medicine were significantly less likely to support preventive TB treatment in health care workers in general or for them personally if they would have evidence of LTBI compared to other specialties (p = 0.001). Only 13% (14/106) of respondents with evidence of LTBI indicated that they had been offered preventive TB treatment. Twenty-one percent (64/306) of respondents indicated that they did not know the difference between active and latent TB. Among staff who had undergone testing for LTBI, only 33% (75/230) felt adequately informed about the meaning of their test results. Discussion. Hospital staff in general had positive attitudes towards preventive TB treatment, but actual treatment rates were low and perceived knowledge about LTBI was insufficient among a significant proportion of staff. The gap between high support for preventive TB treatment among staff and low treatment rates needs to be addressed. Better education on the concept of LTBI and the meaning of screening test results is required. PMID:26966667

  5. Active detection of tuberculosis and paragonimiasis in the remote areas in North-Eastern India using cough as a simple indicator.

    PubMed

    Rekha Devi, Kangjam; Narain, Kanwar; Mahanta, Jagadish; Deori, Rumi; Lego, Kabang; Goswami, Dibyajyoti; Kumar Rajguru, Sanjib; Agatsuma, Takeshi

    2013-04-01

    One of the essential steps in targeting tuberculosis (TB) intervention is early diagnosis and treatment of patients by reducing the reservoir of infection in the community. In the North-Eastern (NE) region of India pulmonary TB and paragonimiasis are overlapping public health issues. We performed a cross-sectional study in 63 remote villages from the two states Arunachal Pradesh (AP) and Assam to determine the prevalence of undiagnosed TB and paragonimiasis cases using cough as a simple indicator. In AP, 2961 individuals aged five years and above were examined and 1108 (37·4%) were found to have cough for one week or more. Of the 417 individuals who provided sputum, 11 (2·64%) were smear positive for acid-fast bacilli (AFB). All these cases were yet undiagnosed, thus the prevalence of new smear positive TB in AP was 0·37%. In Assam on the other hand 331 (23·5%) subjects out of 1410 individuals who were examined had a cough for one week or more and of the 112 individuals who provided sputum, 13 (11·6%) were smear positive for AFB. The prevalence of new smear positive TB cases was 0·78% in Assam. Sero-positivity of paragonimiasis in coughers of AP was 7·6% (n = 1091), which was significantly higher (p < 0·01) as compared to that in Assam (1·2%, n = 321). The findings of the present study suggest that TB remains a major public health concern in the NE region of India especially in the remote places and there is need to strengthen early case detection of TB. PMID:23683370

  6. 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

  7. 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

  8. Multidrug-resistant tuberculosis: Treatment and outcomes of 93 patients

    PubMed Central

    Brode, Sarah K; Varadi, Robert; McNamee, Jane; Malek, Nina; Stewart, Sharon; Jamieson, Frances B; Avendano, Monica

    2015-01-01

    BACKGROUND: Tuberculosis (TB) remains a leading cause of death worldwide and the emergence of multidrug-resistant TB (MDR TB) poses a threat to its control. There is scanty evidence regarding optimal management of MDR TB. The majority of Canadian cases of MDR TB are diagnosed in Ontario; most are managed by the Tuberculosis Service at West Park Healthcare Centre in Toronto. The authors reviewed 93 cases of MDR TB admitted from January 1, 2000 to December 31, 2011. RESULTS: Eighty-nine patients were foreign born. Fifty-six percent had a previous diagnosis of TB and most (70%) had only pulmonary involvement. Symptoms included productive cough, weight loss, fever and malaise. The average length of inpatient stay was 126 days. All patients had a peripherally inserted central catheter for the intensive treatment phase because medications were given intravenously. Treatment lasted for 24 months after bacteriologic conversion, and included a mean (± SD) of 5±1 drugs. A successful outcome at the end of treatment was observed in 84% of patients. Bacteriological conversion was achieved in 98% of patients with initial positive sputum cultures; conversion occurred by four months in 91%. CONCLUSIONS: MDR TB can be controlled with the available anti-TB drugs. PMID:25493698

  9. 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

  10. Novel Adjunctive Therapies for the Treatment of Tuberculosis

    PubMed Central

    Ordonez, A.A.; Maiga, M.; Gupta, S.; Weinstein, E.A.; Bishai, W.R.; Jain, S.K.

    2015-01-01

    Despite significant efforts to control tuberculosis (TB), the disease remains a major global threat, with an estimated 8.6 million new cases and 1.3 million deaths in 2012 alone. Significant treatment challenges include HIV co-infection, the dramatic rise of multidrug-resistant TB and the vast reservoir of latently infected individuals, who will develop active disease years after the initial infection. The long duration of chemotherapy also remains a major barrier to effective large scale treatment of TB. Significant advances are being made in the development of shorter and effective TB drug regimens and there is growing evidence that host-directed and “non-antimicrobial” pathogen-directed therapies, could serve as novel approaches to enhance TB treatments. This review highlights the rationale for using these therapies and summarizes some of the progress in this field. PMID:24236454

  11. 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. PMID:25929762

  12. Predicting results of mycobacterial culture on sputum smear reversion after anti-tuberculous treatment: a case control study

    PubMed Central

    2010-01-01

    Background Little is currently known regarding sputum smear reversion (acid-fast smear becomes positive again after negative conversion) during anti-tuberculous treatment. This study aimed to evaluate its occurrence in patients with pulmonary tuberculosis (TB) and identify factors predicting results of mycobacterial culture for smear-reversion of sputum samples. Methods The retrospective review was performed in a tertiary referral center and a local teaching hospital in Taiwan. From 2000 to 2007, patients with smear-positive culture-confirmed pulmonary TB experiencing smear reversion after 14 days of anti-tuberculous treatment were identified. Results The 739 patients with smear-positive pulmonary TB had 74 (10%) episodes of sputum smear reversion that grew Mycobacterium tuberculosis in 22 (30%) (Mtb group). The remaining 52 episodes of culture-negative sputum samples were classified as the non-Mtb group. The anti-tuberculous regimen was modified after confirming smear reversion in 15 (20%). Fourteen episodes in the Mtb group and 15 in the non-Mtb group occurred during hospitalization. All were admitted to the negative-pressure rooms at the time of smear reversion. Statistical analysis showed that any TB drug resistance, smear reversion within the first two months of treatment or before culture conversion, and the absence of radiographic improvement before smear reversion were associated with the Mtb group. None of the smear reversion was due to viable M. tuberculosis if none of the four factors were present. Conclusions Sputum smear reversion develops in 10% of patients with smear-positive pulmonary TB, with 30% due to viable M. tuberculosis bacilli. Isolation and regimen modification may not be necessary for all drug-susceptible patients who already have radiographic improvement and develop smear reversion after two months of treatment or after sputum culture conversion. PMID:20205743

  13. 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 ...

  14. Tuberculosis.

    PubMed

    Tiruviluamala, Parvathi; Reichman, Lee B

    2002-01-01

    Tuberculosis is an infectious disease caused by bacteria in the Mycobacterium tuberculosis complex. Of these, the most common species to infect humans is M. tuberculosis. The TB bacillus is an extremely successful human pathogen, infecting two billion persons worldwide; an estimated 2 to 3 million people die from tuberculosis each year. In the United States, TB rates decreased steadily at the rate of 5% per year from 1953 until 1985 when the trend reversed, with the number of TB cases peaking in 1992. Outbreaks of multidrug-resistant TB (MDR TB) were reported, and these cases were documented to be transmitted in nosocomial and congregate settings, including hospitals and prisons. AIDS patients infected with M. tb developed disease rapidly, and case-fatality rates of >80% were noted in those infected with multidrug-resistant M. tb. Intensive intervention, at enormous cost, caused the number of TB cases to decline. This article discusses factors that led to the increase in TB cases, their subsequent decline, and measures needed in the future if TB is to be eliminated in the United States. PMID:11910069

  15. [Tuberculosis infection control--recommendations of the DZK].

    PubMed

    Ziegler, R; Just, H-M; Castell, S; Diel, R; Gastmeier, P; Haas, W; Hauer, B; Loytved, G; Mielke, M; Moser, I; Nienhaus, A; Richter, E; Rüden, H; Rüsch-Gerdes, S; Schaberg, T; Wischnewski, N; Loddenkemper, R

    2012-05-01

    The epidemiological situation of tuberculosis (TB) in Germany has improved considerably during the past few years. However, those in unprotected contact with infectious tuberculosis patients frequently and/or over longer periods of time and/or intensively continue to have a higher risk for TB infection. Rapid diagnosis, prompt initiation of effective treatment, and adequate infection control measures are of particular importance to prevent infection. The present recommendations depict the essentials of infection control as well as specific measures in the hospital (isolation, criteria for its duration and technical requirements, types of respiratory protection, disinfection measures, waste disposal). The specific requirements for outpatients (medical practice), at home, for ambulance services, and in congregate settings, including prisons, are also addressed. Compared with the previous recommendations the pattern of respiratory protection measures has been simplified. As a rule, hospital staff and those visiting infectious tuberculosis patients are advised to wear respiratory protection that satisfies the criteria of FFP2-masks (DIN EN 149), while patients should wear mouth-nose protectors (surgical masks) in the presence of others and outside the isolation room. A detailed depiction of criteria for isolation and its duration in smear positive and only culturally confirmed pulmonary tuberculosis has been added. PMID:22294284

  16. Elucidating Novel Serum Biomarkers Associated with Pulmonary Tuberculosis Treatment

    PubMed Central

    De Groote, Mary A.; Nahid, Payam; Jarlsberg, Leah; Johnson, John L.; Weiner, Marc; Muzanyi, Grace; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

    2013-01-01

    In an unbiased approach to biomarker discovery, we applied a highly multiplexed proteomic technology (SOMAscan, SomaLogic, Inc, Boulder, CO) to understand changes in proteins from paired serum samples at enrollment and after 8 weeks of TB treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in the Center for Disease Control and Prevention’s Tuberculosis Trials Consortium (TBTC) Study 29. This work represents the first large-scale proteomic analysis employing modified DNA aptamers in a study of active tuberculosis (TB). We identified multiple proteins that exhibit significant expression differences during the intensive phase of TB therapy. There was enrichment for proteins in conserved networks of biological processes and function including antimicrobial defense, tissue healing and remodeling, acute phase response, pattern recognition, protease/anti-proteases, complement and coagulation cascade, apoptosis, immunity and inflammation pathways. Members of cytokine pathways such as interferon-gamma, while present, were not as highly represented as might have been predicted. The top proteins that changed between baseline and 8 weeks of therapy were TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, and LBP. The novel proteins elucidated in this work may provide new insights for understanding TB disease, its treatment and subsequent healing processes that occur in response to effective therapy. PMID:23637781

  17. 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

  18. Infection Control for Drug-Resistant Tuberculosis: Early Diagnosis and Treatment Is the Key.

    PubMed

    van Cutsem, Gilles; Isaakidis, Petros; Farley, Jason; Nardell, Ed; Volchenkov, Grigory; Cox, Helen

    2016-05-15

    Multidrug-resistant (MDR) tuberculosis, "Ebola with wings," is a significant threat to tuberculosis control efforts. Previous prevailing views that resistance was mainly acquired through poor treatment led to decades of focus on drug-sensitive rather than drug-resistant (DR) tuberculosis, driven by the World Health Organization's directly observed therapy, short course strategy. The paradigm has shifted toward recognition that most DR tuberculosis is transmitted and that there is a need for increased efforts to control DR tuberculosis. Yet most people with DR tuberculosis are untested and untreated, driving transmission in the community and in health systems in high-burden settings. The risk of nosocomial transmission is high for patients and staff alike. Lowering transmission risk for MDR tuberculosis requires a combination approach centered on rapid identification of active tuberculosis disease and tuberculosis drug resistance, followed by rapid initiation of appropriate treatment and adherence support, complemented by universal tuberculosis infection control measures in healthcare facilities. It also requires a second paradigm shift, from the classic infection control hierarchy to a novel, decentralized approach across the continuum from early diagnosis and treatment to community awareness and support. A massive scale-up of rapid diagnosis and treatment is necessary to control the MDR tuberculosis epidemic. This will not be possible without intense efforts toward the implementation of decentralized, ambulatory models of care. Increasing political will and resources need to be accompanied by a paradigm shift. Instead of focusing on diagnosed cases, recognition that transmission is driven largely by undiagnosed, untreated cases, both in the community and in healthcare settings, is necessary. This article discusses this comprehensive approach, strategies available, and associated challenges. PMID:27118853

  19. 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

  20. 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

  1. The timing of death in patients with tuberculosis who die during anti-tuberculosis treatment in Andhra Pradesh, South India

    PubMed Central

    2011-01-01

    Background India has 2.0 million estimated tuberculosis (TB) cases per annum with an estimated 280,000 TB-related deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i) treatment outcomes including the number who died while on treatment, ii) the month of death and iii) characteristics associated with "early" death, occurring in the initial 8 weeks of treatment. Methods This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs) in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children) registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results There were 8,240 TB patients (5183 males) of whom 492 (6%) were known to have died during treatment. Case-fatality was higher in those previously treated (12%) and lower in those with extra-pulmonary TB (2%). There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with "early death". Conclusion In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i) the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii) co-morbidities, such as HIV/AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed. PMID:22166132

  2. 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

  3. A prospective study of tuberculosis drug susceptibility in sabah, malaysia, and an algorithm for management of isoniazid resistance.

    PubMed

    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

  4. A contact investigation of the transmission of Mycobacterium tuberculosis from a nurse working in a newborn nursery and maternity ward.

    PubMed

    Ohno, Hitoshi; Ikegami, Yumiko; Kishida, Kenji; Yamamoto, Yoshiaki; Ikeda, Nobuaki; Taniguchi, Takashi; Ikeda, Takeshi; Sato, Atsuo; Kurasawa, Takuya; Miyanomae, Ken

    2008-02-01

    A nurse working in a newborn nursery and maternity ward developed 3+ smear-positive lung tuberculosis. The hospital infection control committee, in collaboration with the local public health and welfare center, conducted a contact investigation. The infection period was defined as April to August 2006. The investigation included 109 infant and mother pairs, 28 children aged under 10 years and their guardians, 62 coworkers, and 63 household visitors to the ward. Tuberculosis infection in infants and children aged under 5 years was primarily determined by tuberculin skin test (TST), while subjects aged 5 years or more were tested using QuantiFERON-TB Gold (QFT). The first investigation, in August 2006, was conducted in all subjects, and the second investigation, in October 2006, targeted selected subjects. No infants were TST-positive. Two children aged 1 year or under, vaccinated with bacillus Calmette-Guérin, were positive for TST, as determined by the criteria of the Japan Anti-Tuberculosis Association; however, other tests for tuberculosis were negative. Of the 13 QFT-positive adult subjects, 1 mother and 2 coworkers could have become infected with Mycobacterium tuberculosis through exposure to the index nurse. Fifty-four infants and 6 children underwent "window-period" prophylaxis, and 4 adults completed 6-month prophylactic treatment with isoniazid. To date, no secondary cases of tuberculosis disease have occurred. PMID:18297454

  5. 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

  6. 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

  7. Emerging strategies for the treatment of pulmonary tuberculosis: promise and limitations?

    PubMed Central

    Yew, Wing Wai; Koh, Won-Jung

    2016-01-01

    A worsening scenario of drug-resistant tuberculosis has increased the need for new treatment strategies to tackle this worldwide emergency. There is a pressing need to simplify and shorten the current 6-month treatment regimen for drug-susceptible tuberculosis. Rifamycins and fluoroquinolones, as well as several new drugs, are potential candidates under evaluation. At the same time, treatment outcomes of patients with drug-resistant tuberculosis should be improved through optimizing the use of fluoroquinolones, repurposed agents and newly developed drugs. In this context, the safety and tolerance of new therapeutic approaches must be addressed. PMID:26767853

  8. Latent tuberculosis infection: screening and treatment in an urban setting.

    PubMed

    Morano, Jamie P; Walton, Mary R; Zelenev, Alexei; Bruce, R Douglas; Altice, Frederick L

    2013-10-01

    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. Utilizing questionnaire data from a comprehensive mobile healthcare clinic in New Haven, CT from 2003 to July 2011, a total of 2,523 completed tuberculin skin tests (TSTs) resulted in 356 new LTBIs. Multivariate logistic regression correlated covariates of the two outcomes (a) initiation of isoniazid preventative therapy (IPT) and (b) completion of 9 months of IPT. Of the 357 newly positive TSTs, 86.3 % (n = 308) completed screening chest radiographs (CXRs): 90.3 % (n = 278) were normal, and 0.3 % (n = 1) had 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 self-administered therapy (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), employed (p < 0.0001), uninsured (p = 0.014), and have stable housing (p = 0.002), 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). 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

  9. 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

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

    PubMed

    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

    2016-05-01

    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

  11. Epidemiology and control of tuberculosis in the Western Pacific Region: analysis of 2012 case notification data.

    PubMed

    Hiatt, Tom; Nishikiori, Nobuyuki

    2014-01-01

    Tuberculosis (TB) control in the World Health Organization (WHO) Western Pacific Region has seen substantial progress in the last decade, with a 33% reduction in prevalent TB cases since 2000. The burden remains immense, however, and national TB programmes must evolve and adapt to build upon these gains. Through routine surveillance, countries and areas in the Region reported 1.4 million TB cases in 2012. The case notification rate increased in the early 2000s, appears to have stabilized in recent years and is in decline for all forms and new smear-positive cases. The age and sex breakdown for smear-positive TB case rates by country shows generally higher rates with increased age and declining rates over time for all age groups. Treatment success remains high in the Region, with 15 countries reaching or maintaining an 85% success rate. HIV testing among TB patients has increased gradually along with a slow decline in the number of HIV-positive patients found. The trend of TB notification is heavily influenced by programmatic improvements in many countries and rapidly changing demographics. It appears that cases are being found earlier as reflected in declining rates of smear-positive TB and steady rates of TB in all forms. WHO estimates depict a decline in TB incidence in the Region. HIV testing, while still low, has increased substantially in recent years, with essential TB/HIV services expanding in many countries. TB surveillance data, within inherent limitations, is an important source of programmatic and epidemiological information. Careful interpretation of these findings can provide useful insight for programmatic decision-making. PMID:24734214

  12. Treatment of extensively drug-resistant tuberculosis and role of the pharmacist.

    PubMed

    Mitrzyk, Beatriz Manzor

    2008-10-01

    Abstract Outbreaks of extensively drug-resistant tuberculosis (XDR-TB) in developing countries and recent headlines of an American traveling with a resistant variant of tuberculosis have brought XDR-TB into the spotlight. The World Health Organization and the United States Centers for Disease Control and Prevention have identified XDR-TB as a serious public health threat and are mandating increased efforts at control of tuberculosis. Although XDR-TB is believed to be no more infectious than other variants of tuberculosis, infection with and spread of XDR-TB are concerning because of the ineffectiveness, toxicity, and cost of the available tuberculosis treatment options. Pharmacists may not be aware of the recent trends in tuberculosis resistance or of the impact that they can have on educating the public about this disease. To gain a better understanding of this disease and the potential roles for pharmacists in public health awareness of tuberculosis and in the care of patients with and at risk for this disease, we undertook an extensive search of the Internet, including Web sites of tuberculosis advocacy groups, and of MEDLINE from January 1968-March 2008. Currently, XDR-TB infection is uncommon in the United States, but if history is any indication, there is a high potential for an outbreak or epidemic. The XDR-TB variant has emerged from mismanaging multidrug-resistant tuberculosis, treating tuberculosis with too few drugs, using less effective second-line drugs, and not educating patients about the dangers of nonadherence. With only limited hopes of a novel effective drug combination regimen, use of available antimycobacterial drugs needs to be optimized. Pharmacists can be key players in the prevention and treatment of tuberculosis by promoting adherence, assessing patients for risk factors for resistant disease, providing information about disease control and prevention, and monitoring for effectiveness, adverse effects, and drug interactions. PMID:18823220

  13. Utility of PCR in diagnosing pulmonary tuberculosis.

    PubMed Central

    Bennedsen, J; Thomsen, V O; Pfyffer, G E; Funke, G; Feldmann, K; Beneke, A; Jenkins, P A; Hegginbothom, M; Fahr, A; Hengstler, M; Cleator, G; Klapper, P; Wilkins, E G

    1996-01-01

    At present, the rapid diagnosis of pulmonary tuberculosis rests with microscopy. However, this technique is insensitive and many cases of pulmonary tuberculosis cannot be initially confirmed. Nucleic acid amplification techniques are extremely sensitive, but when they are applied to tuberculosis diagnosis, they have given variable results. Investigators at six centers in Europe compared a standardized PCR system (Amplicor; Roche) against conventional culture methods. Defined clinical information was collected. Discrepant samples were retested, and inhibition assays and backup amplification with a separate primer pair were performed. Mycobacterium tuberculosis complex organisms were recovered from 654 (9.1%) of 7,194 samples and 293 (7.8%) of 3,738 patients. Four hundred fifty-two of the M. tuberculosis isolates from 204 patients were smear positive and culture positive. Among the culture-positive specimens, PCR had a sensitivity of 91.4% for smear-positive specimens and 60.9% for smear-negative specimens, with a specificity of 96.1%. Analysis of 254 PCR-positive, culture-negative specimens with discrepant results revealed that 130 were from patients with recently diagnosed tuberculosis and 94 represented a presumed laboratory error. Similar analysis of 118 PCR-negative, culture-positive specimens demonstrated that 27 discrepancies were due to presumed uneven aliquot distribution and 11 were due to presumed laboratory error; PCR inhibitors were detected in 8 specimens. Amplicor enables laboratories with little previous experience with nucleic acid amplification to perform PCR. Disease in more than 60% of the patients with tuberculosis with smear-negative, culture-positive specimens can be diagnosed at the time of admission, and potentially all patients with smear-positive specimens can immediately be confirmed as being infected with M. tuberculosis, leading to improved clinical management. PMID:8735089

  14. Evaluation of disease patterns, treatment and prognosis of tuberculosis in AIDS patient.

    PubMed

    Atomiya, Angela Naomi; Uip, David Emerson; Leite, Olavo Henrique Munhoz

    2002-02-01

    Patterns of disease, diagnosis, treatment and prognosis of tuberculosis in 100 patients co-infected with AIDS at Casa da AIDS clinic was studied. Demographic characteristics were as follows: 76 male patients, 24 female patients, 67 caucasian, average 35.8 years-old (SD +/- 8.5). Sexual transmission of HIV was reported in 68 patients. Pulmonary tuberculosis was seen in 40 patients, extrapulmonary in 11, and combined in 49 patients. In 63 patients, TCD(4)(+) counts were below 200/mm(3) when tuberculosis was diagnosed. Fifty-five patients had their diagnoses confirmed by bacteriological identification of Mycobacterium; either through direct observation and/or culture. Tuberculosis was treated with rifampin, isoniazid and pyrazinamide in 60 patients, reinforced treatment in 14 and alternative treatment in the other 13 patients. Tuberculosis therapy lasted up to 9 months in 66% of the patients. Fifty-four patients were treated with a two-drug antiretroviral regimen and the remaining 46 patients received a triple regimen, which included a protease inhibitor. Among the latter, 35 patients were co-treated with rifampin. The occurrence of hepatic liver enzyme abnormalities was statistically related to alternative antiretroviral regimens (p = 0.01) and to the co-administration of rifampin and protease inhibitor (p = 0.019). Clinical resolution of tuberculosis was obtained in 74 patients. Twelve patients died during tuberculosis treatment. Resolution of tuberculosis was statistically significant related to antituberculosis treatment adherence (p = 0.001). The risk of no response to the treatment was 1.84 times more frequent among patients treated with alternative regimens regardless of the duration of the therapy. We conclude that the characteristics of tuberculosis in HIV infected patients requires that special attention be directed to the types and duration of both antiretroviral and anti-TB therapy in order to achieve the highest level of care. PMID:11980601

  15. Reflections on tuberculosis diagnosis and treatment outcomes in Ghana

    PubMed Central

    2013-01-01

    Background Available evidence in Ghana shows the implementation of tuberculosis (TB) control activities efforts since the beginning of the 1900s. In spite of that, TB continues to be one of the common diseases in the country. In 1994, local and international policy windows opened for renewed strategies for the control of TB. This paper explores some of the approaches which have been in place since 1994 and their implications for treatment outcomes. Methods The study combines quantitative and qualitative data. The quantitative data consist of treatment outcome from 1997–2010 and the qualitative data are derived from in-depth interviews with some staff of the TB control programme. Poisson regression and inductive coding were applied to the quantitative and qualitative data respectively. Results Reported cure rates increased from 43.6% to 87.7% between 1997 and 2010. The data from the in-depth interviews (IDIs) suggested that improvements in diagnosis, community TB care, stigma reduction among community and health workers towards TB patients, the public-private partnership, and the enablers’ package contributed to the improved better treatment outcomes, particularly from 2008. Conclusions Lessons learnt include the achievement of objectives with varying strategies and stakeholder interventions. Further studies would be needed to quantify the contributions of the various interventions to help determine those that are cost effective as well as efficient and effective for TB control. PMID:23971675

  16. 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

  17. [New Drugs for the Treatment of Multidrug-resistant Tuberculosis (MDR-TB)].

    PubMed

    Schaberg, T; Otto-Knapp, R; Bauer, T

    2015-05-01

    This article summarizes the state of development of new drugs for the treatment of multidrug-resistant tuberculosis. We focused on delamanid, bedaquiline, pretomanid, SQ 109 and sutezolid. PMID:25970122

  18. [Tuberculosis in compromised hosts].

    PubMed

    2003-11-01

    among patients with pulmonary tuberculosis was 8.4 percent. The mean age of gastric resection was 50.2 +/- 16.6 years, and the mean interval from gastrectomy to pulmonary tuberculosis was 13.6 +/- 11.0 years. On admission to our hospital, 34 out of 55 cases were smear positive by sputum examination for acid-fast bacilli and 39 cases had cavitary lesions on chest X-ray. Gastrectomy was done due to carcinoma of the stomach in 31 cases, gastric and/or duodenal ulcer in 21 cases, adenomatous polyp in two cases, and accidental injury in one case. 52 patients improved, but three cases died due to pulmonary tuberculosis. No one had recurrence of carcinoma of the stomach. Body weight, Body Mass Index, Prognostic Nutritional Index (PNI; 10x serum albumin concentration +0.005 x peripheral lymphocyte count) which was proposed by Onodera, serum albumin level and serum total cholesterol level were lower in the gastrectomy group than in the non-gastrectomy group. I calculated the odds of tuberculosis among gastrectomy patients to be 3.8 times that of appropriate controls. This study confirms that gastrectomy is one of the risk factor(s) of tuberculosis. However, whether gastrectomy in itself is a risk factor or whether it is secondarily associated with another risk factor such as underweight status and/or inadequate nutrition following surgery remains unclear. 3. Immunodefficiency and tuberculosis in dialysis patients: Hajime INAMOTO (Division of Dialysis, Keio University School of Medicine). The patients who have renal insufficiency is fatal, but they can live much longer by dialysis. The number of lymphocytes of the patients whose serum creatinine was 10 mg/dl or more has decreased to about 50% of the people who have normal kidney. When the lymphocyte was cultured after it was stimulated with PHA, the DNA synthesis of the patients' lymphocyte was much lower than that of the modest people's. In the dialysis food, the nutrient such as vitamins, minerals, etc. were lacked. The density

  19. 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. PMID:25189560

  20. 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

  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. Bedaquiline for the treatment of resistant tuberculosis: promises and pitfalls.

    PubMed

    Kakkar, Ashish Kumar; Dahiya, Neha

    2014-07-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB) is hindered by limited efficacy and significant toxicity of second-line drugs. The need for new therapeutic options is critical to combat the global MDR-TB epidemic. Bedaquiline is a novel oral diarylquinoline approved by Food and Drug administration (FDA) for the treatment of adults with pulmonary MDR-TB on the basis of Phase IIb trial data under the provisions of the accelerated approval regulations for serious or life-threatening conditions. The FDA advisory committee members voted unanimously on efficacy data based on surrogate measures, however they were split on the issues of safety of bedaquiline. Main safety concerns include QT interval prolongation, hepatic related adverse events, and excess mortality in bedaquiline treated patients. While bedaquiline approval is a story of many firsts and certainly a welcome addition to the existing arsenal of anti-TB agents, a cautiously optimistic approach is required to assess the risk benefit profile of the drug. Acceleration of further Phase III trials and clinical studies is imperative, as is timely analysis of emerging data on the real world use of the drug. This mini review outlines the clinical pharmacology of bedaquiline highlighting the potential promises and challenges that implicate the risk benefit profile of drug. PMID:24841672

  3. 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

  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. 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

  6. 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

  7. 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

  8. 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

  9. Understanding latent tuberculosis: the key to improved diagnostic and novel treatment strategies

    PubMed Central

    Esmail, Hanif; Barry, Clifton E; Wilkinson, Robert J

    2012-01-01

    Treatment of latent tuberculosis (LTBI) is a vital component of tuberculosis elimination but is not efficiently implemented with available diagnostics and therapeutics. The tuberculin skin test and interferon gamma release assays can inform that infection has occurred but do not prove that it persists. Treatment of LTBI with isoniazid targets actively replicating bacilli but not non-replicating populations, prolonging treatment duration. Developing more predictive diagnostic tests and treatments of shorter duration requires a greater understanding of the biology of latent tuberculosis, from both host and bacillary perspectives. In this article we discuss the basis of current diagnosis and treatment of LTBI and review recent developments in understanding the biology of latency that may enable future improved diagnostic and treatment strategies. PMID:22198298

  10. 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

  11. Does Alcohol Consumption during Multidrug-resistant Tuberculosis Treatment Affect Outcome?

    PubMed Central

    Duraisamy, Karthickeyan; Mrithyunjayan, Sunilkumar; Ghosh, Smita; Nair, Sreenivas Achuthan; Balakrishnan, Shibu; Subramoniapillai, Jayasankar; Oeltmann, John E.; Moonan, Patrick K.; Kumar, Ajay M. V.

    2015-01-01

    Rationale India reports the largest number of multidrug-resistant tuberculosis cases in the world; yet, no longitudinal study has assessed factors related to treatment outcomes under programmatic conditions in the public sector. Objectives To describe demographic, clinical, and risk characteristics associated with treatment outcomes for all patients with multidrug-resistant tuberculosis registered in the Revised National Tuberculosis Control Programme, Kerala State, India from January 1, 2009 to June 30, 2010. Methods Cox regression methods were used to calculate adjusted hazard ratios with 95% confidence intervals (CIs) to assess factors associated with an unsuccessful treatment outcome. Measurements and Main Results Of 179 patients with multidrug-resistant tuberculosis registered, 112 (63%) had successful treatment outcomes (77 bacteriologically cured, 35 treatment completed) and 67 (37%) had unsuccessful treatment outcomes (30 died, 26 defaulted, 9 failed treatment, 1 stopped treatment because of drug-related adverse events, and 1 developed extensively drug-resistant tuberculosis). The hazard for unsuccessful outcome was significantly higher among patients who consumed alcohol during treatment (adjusted hazard ratio, 4.3; 95% CI, 1.1–17.6) than those who did not. Persons who consumed alcohol during treatment, on average, missed 18 more intensive-phase doses (95% CI, 13–22) than those who did not. Although many patients had diabetes (33%), were ever smokers (39%), or had low body mass index (47%), these factors were not associated with outcome. Conclusion Overall treatment success was greater than global and national averages; however, outcomes among patients consuming alcohol remained poor. Integration of care for multidrug-resistant tuberculosis and alcoholism should be considered to improve treatment adherence and outcomes. PMID:24735096

  12. HIV-associated tuberculosis in developing countries: clinical features, diagnosis, and treatment.

    PubMed Central

    Raviglione, M. C.; Narain, J. P.; Kochi, A.

    1992-01-01

    This article reviews the clinical aspects and diagnosis of HIV-associated tuberculosis in developing countries, and summarizes WHO's recommendations for treatment. According to WHO estimates (early 1992) over 4 million persons worldwide have been infected with HIV and tuberculosis; 95% of them are in the developing countries. Clinical features of HIV-associated pulmonary tuberculosis in adults are frequently atypical, particularly in the late stage of HIV infection, with non-cavitary disease, lower lobe infiltrates, hilar lymphadenopathy and pleural effusion. More typical post-primary tuberculosis with upper lobe infiltrates and cavitations is seen in the earlier stages of HIV infection. Extrapulmonary tuberculosis is reported more frequently, despite the difficulties in diagnosing it. WHO's recent guidelines recommend 6-month short-course chemotherapy with isoniazid, rifampicin, pyrazinamide and ethambutol for patients with HIV-associated tuberculosis. The older 12-month regimen without rifampicin is much less effective. Streptomycin should not be used, because of the risk of transmitting blood-borne pathogens through contaminated needles. Thioacetazone should be abandoned, because of severe adverse reactions observed among HIV-infected patients. The roles of preventive chemotherapy and BCG vaccination for prevention of tuberculosis are also briefly discussed. PMID:1394786

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26197334

  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. Scaling-up treatment for HIV/AIDS: lessons learned from multidrug-resistant tuberculosis.

    PubMed

    Gupta, Rajesh; Irwin, Alexander; Raviglione, Mario C; Kim, Jim Yong

    2004-01-24

    The UN has launched an initiative to place 3 million people in developing countries on antiretroviral AIDS treatment by end 2005 (the 3 by 5 target). Lessons for HIV/AIDS treatment scale-up emerge from recent experience with multidrug-resistant tuberculosis. Expansion of treatment for multidrug-resistant tuberculosis through the multipartner mechanism known as the Green Light Committee (GLC) has enabled gains in areas relevant to 3 by 5, including policy development, drug procurement, rational use of drugs, and the strengthening of health systems. The successes of the GLC and the obstacles it has encountered provide insights for building sustainable HIV/AIDS treatment programmes. PMID:14751708

  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. Changes in Avidity and Level of Immunoglobulin G Antibodies to Mycobacterium tuberculosis in Sera of Patients Undergoing Treatment for Pulmonary Tuberculosis

    PubMed Central

    Pereira Arias-Bouda, Lenka M.; Kuijper, Sjoukje; Van Der Werf, Anouk; Nguyen, Lan N.; Jansen, Henk M.; Kolk, Arend H. J.

    2003-01-01

    Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens. PMID:12853408

  19. Tonsillar tuberculosis: a forgotten clinical entity.

    PubMed

    Das, Anirban; Das, Sibes K; Pandit, Sudipta; Basuthakur, Sumitra

    2015-01-01

    Tuberculosis of tonsils is an extremely rare variety of extra-pulmonary tuberculosis which frequently simulates the tonsillar malignancy, especially in elderly individuals. Secondary form is more common than primary one, and in present day, contact with the infected sputum or saliva in a case of sputum smear positive pulmonary tuberculosis is the main source of the disease. Chronic or recurrent tonsillitis with enlarged tonsils and sore throat is the main clinical presentation. As it is very difficult to differentiate it from tonsillar malignancy on clinical ground, histopathological examination of the tissue is must for the diagnosis of tonsillar TB. Antitubercular therapy is adequate for its successful resolution. Here, we report a primary form of tonsillar tuberculosis in a 76-year-old male, in whom, no pulmonary tuberculosis was documented. PMID:25811002

  20. Old Drugs, New Purpose: Retooling Existing Drugs for Optimized Treatment of Resistant Tuberculosis

    PubMed Central

    Dooley, Kelly E.; Mitnick, Carole D.; Ann DeGroote, Mary; Obuku, Ekwaro; Belitsky, Vera; Hamilton, Carol D.; Makhene, Mamodikoe; Shah, Sarita; Brust, James C. M.; Durakovic, Nadza; Nuermberger, Eric

    2012-01-01

    Treatment of drug-resistant tuberculosis is hindered by the high toxicity and poor efficacy of second-line drugs. New compounds must be used together with existing drugs, yet clinical trials to optimize combinations of drugs for drug-resistant tuberculosis are lacking. We conducted an extensive review of existing in vitro, animal, and clinical studies involving World Health Organization–defined group 1, 2, and 4 drugs used in drug-resistant tuberculosis regimens to inform clinical trials and identify critical research questions. Results suggest that optimizing the dosing of pyrazinamide, the injectables, and isoniazid for drug-resistant tuberculosis is a high priority. Additional pharmacokinetic, pharmacodynamic, and toxicodynamic studies are needed for pyrazinamide and ethionamide. Clinical trials of the comparative efficacy and appropriate treatment duration of injectables are recommended. For isoniazid, rapid genotypic tests for Mycobacterium tuberculosis mutations should be nested in clinical trials. Further research focusing on optimization of dose and duration of drugs with activity against drug-resistant tuberculosis is paramount. PMID:22615332

  1. 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

  2. Long-term survival of patients with multidrug-resistant tuberculosis according to treatment outcomes.

    PubMed

    Kwak, Nakwon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Yim, Jae-Joon

    2016-07-01

    Survival times of 219 patients diagnosed with multidrug-resistant tuberculosis were calculated and treatment outcomes compared. Mean survival of 20 patients who failed to be cured was 109.8 months (95% confidence interval [CI], 87.4-132.1), shorter than that of 150 patients who were cured (140.4 months; 95% CI, 136.1-144.7; P < .01) and that of 28 patients classified as treatment completed (138.5 months; 95% CI, 131.0-146.1; P = .02). The results demonstrate that patients with multidrug-resistant tuberculosis with poor treatment outcomes live 9 years, on average. PMID:26922891

  3. Targeted drug-resistance testing strategy for multidrug-resistant tuberculosis detection, Lima, Peru, 2005-2008.

    PubMed

    Velásquez, Gustavo E; Yagui, Martin; Cegielski, J Peter; Asencios, Luis; Bayona, Jaime; Bonilla, Cesar; Jave, Hector O; Yale, Gloria; Suárez, Carmen; Atwood, Sidney; Contreras, Carmen C; Shin, Sonya S

    2011-03-01

    The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005-November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household contact, suspected category II failure, early relapse after category I, and multiple previous TB treatments were associated with MDR TB, compared with concurrent regional surveillance data. The proportion of MDR TB detected by using guidelines was higher than that detected by a concurrent national drug-resistance survey, indicating that the strategy effectively identified patients for DST. PMID:21392434

  4. Evaluation of a rapid air thermal cycler for detection of Mycobacterium tuberculosis.

    PubMed Central

    Chapin, K; Lauderdale, T L

    1997-01-01

    The Air Thermal Cycler (ATC) (Idaho Technology, Idaho Falls, Idaho) utilizes the unique technology of small-volume glass capillary tubes and high-velocity air for the heating and cooling medium for the PCR. Standard heat block thermal cycler (HBTC) and ATC performance characteristics were compared for the detection of Mycobacterium tuberculosis. Sensitivity was 100% for all smear-positive, M. tuberculosis culture-positive specimens for both the HBTC and the ATC. Of smear-negative, M. tuberculosis culture-positive specimens, sensitivity was 42.9% with the HBTC and 22.0% with the ATC. Specificity was 100% for both assay systems. Total assay time was 6.5 and 4 h and the reagent cost was 84 and 32 cents for the HBTC and ATC, respectively. The ATC offered an excellent alternative to the traditional HBTC for diagnosis of M. tuberculosis in smear-positive specimens by PCR. PMID:9230404

  5. Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.

    PubMed

    Sharma, Surendra K; Mohan, Alladi; Chauhan, L S; Narain, J P; Kumar, P; Behera, D; Sachdeva, K S; Kumar, Ashok; Agarwal, Priyanka; Awadh, N T; Bansal, Avi; Baruah, S; Baruwa, Pranab; Balasangameshwara, V H; Balasubramanian, Rani; Bhardwaj, A K; Bhargav, Salil; Chadha, Sarabjit; Chaddha, V K; Chhatwal, Manpreet; Da Costa, A L; Dash, D P; Dep, Jaydip; Dhingra, Saroj; Dhooria Harmeet, S; Frieden, T R; Garg, Anil; Granich, Reuben; Gulati, Vinay; Gupta, Deepak; Gupta, Dheeraj; Gupta, K B; Gupta, K N; Jaikishan; Janmeja, A K; Jawahar, M S; Jethani, S L; Jindal, S K; John, K R; Kalra, O P; Kalra, V P; Kannan, A T; Kayshap, S; Keshav Chander, G; Khushwa, S S; Kushwaha, R S; Kumar, Vinod; Laskar, B; Leela Itty Amma, K R; Leuva, A T; Maitra Malay, K; Mesquita, A M; Mathew, Thomas; Mundade, Yamuna; Munje, Radha; Nagpal, Somil; Nagaraja, C; Nair, Sanjeev; Narayanan, O R; Paramasivan, C N; Parmar, Malik; Prasad, Rajendra; Phukan, A C; Prasanna, Raj; Purty, Anil; Ramachandran, Ranjani; Ramachandran, Rajeswari; Ravindran, C; Reddy Raveendra, H R; Sahu, S; Santosha; Sarin, Rohit; Sarkar, Soumya; Sarma, K C; Saxena, P; Sehgal, Shruti; Sharath, N; Sharma, Geetanjali; Sharma, Nandini; Shridhar, P K; Shukla, R S; Singh, Om; Singh, N Tombi; Singh, Varinder; Singla, Rupak; Sinha, Neena; Sinha, Pranay; Sinha, Sanjay; Solanki, Rajesh; Sreenivas, A; Srinath, S; Subhakar, Kandi; Suri, J C; Talukdar, Palash; Tonsing, Jamie; Tripathy, S P; Vaidyanathan, Preetish; Vashist, R P; Venu, K

    2013-02-01

    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

  6. Hypercalcemic encephalopathy in a patient on anti-TB treatment for glandular tuberculosis.

    PubMed

    Abraham, G; Sadasivam, P B; Gaspar, J H; Isphani, N; Lawrence, R

    1992-08-01

    An 84 years old male patient presented with hypercalcemic encephalopathy and mild azotemia while on anti-tuberculous treatment for glandular tuberculosis. He recovered fully during treatment with hydration, intravenous frusemide and oral prednisolone while continuing on the antituberculous therapy. PMID:1308493

  7. Comparison of Results from Inpatient and Outpatient Treatment of Tuberculosis in Republic of Macedonia

    PubMed Central

    Simonovska, Ljiljana; Ilievska-Popovska, Biljana

    2015-01-01

    BACKGROUND: The successful treatment of patients with active tuberculosis is one of the priorities in the Tuberculosis Control Programs. AIM: The aim was to establish whether there was a statistically significant difference in the treatment outcome in patients with tuberculosis who began their initial treatment phase and/or pursued it as inpatient, as opposed to patients with tuberculosis who underwent their entire treatment regime as outpatient. Moreover, our goal was to determine whether there is a statistically significant difference in the outcome from the treatment between patients with tuberculosis who were hospitalized up to one month, two months, or more than two months. MATERIALS AND METHOD: The study includes 355 patients, divided into two groups. The first group, which consists of 219 patients, began their initial treatment phase as inpatient, and then they continued the treatment as outpatient. The second group, 136 patients, underwent their entire treatment as outpatient. The treatment outcome is determined with every patient (cured, treatment completed, treatment default, treatment failed, died, treatment in progress). For the statistical data analysis and for establishing the significance of the findings regarding the differences between the two groups we used the Pearson Chi-Square Test and the Yates Corrected Test. RESULTS: The statistical analysis with the Pearson Chi-Square Test showed that the treatment outcome does not significantly depend on the model of treatment (p = 0.31). The statistical data analysis showed that there is no statistically significant difference in the achievement of conversion of the bacterial result of the sputum at the end of the initial phase of treatment regarding the studied groups (p = 0.89). The statistical data analysis showed that the length of inpatient treatment affects the outcome of the treatment and that the difference is statistically highly significant (p < 0.00005). CONCLUSION: There are no statistically

  8. The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia

    PubMed Central

    Abate, Ebba; Belayneh, Meseret; Gelaw, Aschalew; Idh, Jonna; Getachew, Assefa; Alemu, Shitaye; Diro, Ermias; Fikre, Nigussu; Britton, Sven; Elias, Daniel; Aseffa, Abraham; Stendahl, Olle; Schön, Thomas

    2012-01-01

    Background Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. Methodology Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. Results Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV−/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. Conclusion One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV−/TB group. PMID:22952620

  9. 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

  10. 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

  11. 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

  12. Lab-on-Chip-Based Platform for Fast Molecular Diagnosis of Multidrug-Resistant Tuberculosis

    PubMed Central

    Cabibbe, Andrea M.; Miotto, Paolo; Moure, Raquel; Alcaide, Fernando; Feuerriegel, Silke; Pozzi, Gianni; Nikolayevskyy, Vladislav; Drobniewski, Francis; Niemann, Stefan; Reither, Klaus

    2015-01-01

    We evaluated the performance of the molecular lab-on-chip-based VerePLEX Biosystem for detection of multidrug-resistant tuberculosis (MDR-TB), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and MTBDRplus assay for Mycobacterium tuberculosis complex and rifampin and isoniazid resistance detection on clinical isolates and smear-positive specimens. The speed, user-friendly interface, and versatility make it suitable for routine laboratory use. PMID:26246486

  13. [Present and future of tuberculosis care in regions].

    PubMed

    Shigeto, Eriko

    2012-12-01

    As the incidence of active tuberculosis in Japan declines and the healthcare environment changes, restructuring of the medical care system for tuberculosis is required. According to a questionnaire survey in Hiroshima Prefecture, experiences in tuberculosis (TB) care and knowledge, such as standard treatment and DOT, is insufficient in the local medical institutions designated for tuberculosis care. Regional coordination between the tuberculosis hospital and the regional private practitioners will be one of the important issues in proper TB care. In order to strengthen coordination, Higashi-hiroshima Medical Center (HMC) collaborated with Onomichi Medical Association and the health center having jurisdiction over the area (Tobu Health Center) to create liaison clinical paths for doctors, a booklet for patient education and a medication record named "DOTS note". These liaison paths were provided to the regional practitioner from the health center on discharge and referral from HMC. After the start of regional cooperation, treatment outcome of the cohort of sputum smear positive pulmonary tuberculosis in the region were improved: success; 37.0% to 53.3% (cured; 0% to 40.0%, completed; 37.0% to 13.3%), treatment more than 12 months; 17.4% to 6.7%, died 37.0% to 26.7%. It is considered from experience of the regional cooperation in Hiroshima that regional medical cooperation using liaison paths is helpful to provide proper TB care. Treatment of patients with serious complication(s) is another issue in TB care. For example, only a few TB hospitals can treat the patient who needs hemodialysis, on the other hand, most general hospitals do not treat TB patients, because they have no beds and little knowledge. I think the following measures are effective and necessary for the future TB care: 1) one or more of the general hospitals in each region should provide one or more air-controlled bed(s) to treat TB patients, which can be also used for patients with suspected airborne

  14. Multi Drug and Other Forms of Drug Resistant Tuberculosis Are Uncommon among Treatment Naïve Tuberculosis Patients in Tanzania

    PubMed Central

    Nagu, Tumaini J.; Aboud, Said; Mwiru, Ramadhani; Matee, Mecky; Fawzi, Wafaie; Mugusi, Ferdinand

    2015-01-01

    Background Surveillance and effective management of drug resistance is important to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance rates to first line anti tuberculosis drugs and to describe factors associated with the resistance to any of the first line anti tuberculosis drugs in Dar es Salaam Tanzania. Materials Newly diagnosed, TB patients with neither history of tuberculosis treatment nor isoniazid prophylaxis were included into the study. Sputum specimens were cultured on either mycobacteria growth indicator tube 960 (MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol (GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin, streptomycin and ethambutol was determined by either Lowenstein–Jensen (LJ) medium or mycobacteria growth indicator tube 960 (MGIT 960). Results A total of 933 newly diagnosed TB patients, were included into the study. Multi drug resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to any of the four tested drugs was detected among 54 (5.8%) patients. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3 (0.3%), 13 (1.4%), 9 (1.0%) respectively. Conclusion Primary resistance to first line anti tuberculosis drugs is still low in this setting. Continued vigilance including periodic national surveillance of anti-tuberculosis resistance is recommended. PMID:25849784

  15. Smoking and 2-month culture conversion during anti-tuberculosis treatment

    PubMed Central

    Maciel, E. L.; Brioschi, A. P.; Peres, R. L.; Guidoni, L. M.; Ribeiro, F. K.; Hadad, D. J.; Vinhas, S. A.; Zandonade, E.; Palaci, M.; Dietze, R.; Johnson, J. L.

    2013-01-01

    SUMMARY OBJECTIVE To investigate risk factors for delayed sputum culture conversion to negative during anti-tuberculosis treatment, with an emphasis on smoking. DESIGN Nested case-control study of adults with non-cavitary, culture-confirmed pulmonary tuberculosis (TB) participating in an anti-tuberculosis treatment trial in Brazil. A case of delayed culture conversion was a patient who remained culture-positive after 2 months of treatment. Odds ratios with 95% confidence intervals were calculated. RESULTS Fifty-three cases and 240 control patients were analyzed. Smokers had three-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.007) than non-smokers, while smokers and ex-smokers who smoked >20 cigarettes a day had two-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.045). CONCLUSION Cigarette smoking adversely affects culture conversion during anti-tuberculosis treatment. Support for smoking cessation should be considered to improve outcomes in TB control programs. PMID:23317958

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

    PubMed Central

    Zhao, Yanlin; Rubin, Eric J.

    2016-01-01

    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. PMID:26886068

  17. 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. PMID:26886068

  18. 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

  19. Health system delay in pulmonary tuberculosis treatment in a country with an intermediate burden of tuberculosis: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Delayed diagnosis and treatment of tuberculosis increase both the severity of the disease and the duration of infectivity. A number of studies have addressed the issue of health system delays in the treatment of tuberculosis, but mostly in countries with a high or low incidence of the disease. Our understanding of delay is quite limited in settings with an intermediate burden of tuberculosis. We explore the duration and factors associated with delays in the Croatian health system which has free health care and a sufficient network of health services providing tuberculosis diagnosis and care. Methods A total of 241 consecutive adults with culture-confirmed pulmonary tuberculosis were interviewed in seven randomly selected Croatian counties and their medical records were evaluated. A health system delay was defined as the number of days from the first consultation with a physician to the initiation of anti-tuberculosis treatment. A long delay was defined as a period exceeding the median delay, while an extreme delay was considered to be above the 75th percentile delay. Results The median health system delay was 15 days while the 75th percentile was 42 days (the 5th and 95th percentile being 1 and 105 days respectively). Almost 30% of tuberculosis patients remained undiagnosed for more than 30 days after the initial health care visit. Female patients (p = 0.005), patients with a negative sputum smear (p = 0.002) and patients having symptoms other than the usual ones (0.027) were found to be in significant correlation with a long delay. In a multivariate model, a long delay remained associated with the same variables (p = 0.008, p = 0.003, and p = 0.037, respectively). A significant association was demonstrated between both the female gender (p = 0.042) and a negative sputum smear (p < 0.001) and extreme delay, while only a negative sputum smear (p < 0.001) remained significant in the multivariate analysis. Conclusions Our

  20. Systematic review of randomised controlled trials of strategies to promote adherence to tuberculosis treatment.

    PubMed Central

    Volmink, J.; Garner, P.

    1997-01-01

    OBJECTIVE: To determine the effectiveness of strategies to promote adherence to treatment for tuberculosis. IDENTIFICATION: Searches in Medline (1966 to August 1996), the Cochrane trials register (up to October 1996), and LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud) (1982 to September 1996); screening of references in articles on compliance and adherence; contact with experts in research on tuberculosis and adherence. INCLUSION CRITERIA: Randomised or pseudorandomised controlled trials of interventions to promote adherence with curative or preventive treatment for tuberculosis, with at least one measure of adherence. MAIN OUTCOME MEASURE: Relative risks and 95% confidence intervals for estimates of effect for categorical outcomes. RESULTS: Five trials met the inclusion criteria. The relative risk for tested reminder cards sent to patients who defaulted on treatment was 1.2 (95% confidence interval 1.1 to 1.4), for help given to patients by lay health workers 1.4 (1.1 to 1.8), for monetary incentives offered to patients 1.6 (1.3 to 2.0), for health education 1.2 (1.1 to 1.4), for a combination of a patient incentive and health education 2.4 (1.5 to 3.7) or 1.1 (1.0 to 1.2), and for intensive supervision of staff in tuberculosis clinics 1.2 (1.1 to 1.3). There were no completed trials of directly observed treatment. All of the interventions tested improved adherence. On current evidence it is unclear whether health education by itself leads to better adherence to treatment. CONCLUSIONS: Reliable evidence is available to show some specific strategies improve adherence to tuberculosis treatment, and these should be adopted in health systems, depending on their appropriateness to practice circumstances. Further innovations require testing to help find specific approaches that will be useful in low income countries. Randomised controlled trials evaluating the independent effects of directly observed treatment are awaited. PMID:9418086

  1. 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. PMID:24430455

  2. Extensive Drug Resistance Acquired During Treatment of Multidrug-Resistant Tuberculosis

    PubMed Central

    Cegielski, J. Peter; Dalton, Tracy; Yagui, Martin; Wattanaamornkiet, Wanpen; Volchenkov, Grigory V.; Via, Laura E.; Van Der Walt, Martie; Tupasi, Thelma; Smith, Sarah E.; Odendaal, Ronel; Leimane, Vaira; Kvasnovsky, Charlotte; Kuznetsova, Tatiana; Kurbatova, Ekaterina; Kummik, Tiina; Kuksa, Liga; Kliiman, Kai; Kiryanova, Elena V.; Kim, HeeJin; Kim, Chang-ki; Kazennyy, Boris Y.; Jou, Ruwen; Huang, Wei-Lun; Ershova, Julia; Erokhin, Vladislav V.; Diem, Lois; Contreras, Carmen; Cho, Sang Nae; Chernousova, Larisa N.; Chen, Michael P.; Caoili, Janice Campos; Bayona, Jaime; Akksilp, Somsak; Calahuanca, Gloria Yale; Wolfgang, Melanie; Viiklepp, Piret; Vasilieva, Irina A.; Taylor, Allison; Tan, Kathrine; Suarez, Carmen; Sture, Ingrida; Somova, Tatiana; Smirnova, Tatyana G.; Sigman, Erika; Skenders, Girts; Sitti, Wanlaya; Shamputa, Isdore C.; Riekstina, Vija; Pua, Kristine Rose; Therese, M.; Perez, C.; Park, Seungkyu; Norvaisha, Inga; Nemtsova, Evgenia S.; Min, Seonyeong; Metchock, Beverly; Levina, Klavdia; Lei, Yung-Chao; Lee, Jongseok; Larionova, Elena E.; Lancaster, Joey; Jeon, Doosoo; Jave, Oswaldo; Khorosheva, Tatiana; Hwang, Soo Hee; Huang, Angela Song-En; Gler, M. Tarcela; Dravniece, Gunta; Eum, Seokyong; Demikhova, Olga V.; Degtyareva, Irina; Danilovits, Manfred; Cirula, Anda; Cho, Eunjin; Cai, Ying; Brand, Jeanette; Bonilla, Cesar; Barry, Clifton E.; Asencios, Luis; Andreevskaya, Sofia N.; Akksilp, Rattanawadee

    2014-01-01

    Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16–.47) for XDR tuberculosis, 0.28 (.17–.45) for FQ, and 0.15 (.06–.39) to 0.60 (.34–1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07–.62) for acquired XDR tuberculosis and 0.23 (.09–.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. PMID:25057101

  3. 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.

  4. Treatment of latent tuberculosis infection induces changes in multifunctional Mycobacterium tuberculosis-specific CD4+ T cells.

    PubMed

    Sauzullo, Ilaria; Mengoni, Fabio; Mascia, Claudia; Rossi, Raffaella; Lichtner, Miriam; Vullo, Vincenzo; Mastroianni, Claudio M

    2016-02-01

    To ascertain whether multiparametric flow cytometry assessment of multifunctional Mycobacterium tuberculosis (Mtb)-specific CD4(+) and CD8(+) T cells can distinguish between untreated and treated patients with latent tuberculosis infection (LTBI), we enrolled 14 LTBI subjects treated with isoniazid (INH) therapy, 16 untreated LTBI patients, and 25 healthy controls. The analysis of mono-functional CD4(+) and CD8(+) T cells producing single cytokines showed significant differences only between uninfected and infected LTBI subjects (both treated and untreated). Conversely, the analysis of multifunctional CD4(+) T cells revealed a significant reduction in the frequency of two CD4(+) T cells subsets, those producing IFN-γ, IL-2, and TNF-α simultaneously (triple positive; p = 0.005) and those producing IL-2 alone (p = 0.0359), as well as a shift towards T cells producing only one cytokine in treated as compared to untreated LTBI subjects. Assigning a triple-positive CD4(+) T cells a cut-off >0.082 %, 94 % of untreated LTBI patients were scored as positive, as compared to only 28 % of treated LTBI patients and none of the healthy controls. No significant differences between untreated and treated LTBI subjects in terms of Mtb-specific CD8(+) T cell cytokine profiles (p > 0.05) were identified. The significant changes in the cytokine profiles of Mtb-specific T cells after INH therapy suggest that analysis of multifunctional T cells may be a promising means for the monitoring of LTBI treatment success. PMID:26108901

  5. 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

  6. 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

  7. 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

  8. Feasibility, Yield, and Cost of Active Tuberculosis Case Finding Linked to a Mobile HIV Service in Cape Town, South Africa: A Cross-sectional Study

    PubMed Central

    Kranzer, Katharina; Lawn, Stephen D.; Meyer-Rath, Gesine; Vassall, Anna; Raditlhalo, Eudoxia; Govindasamy, Darshini; van Schaik, Nienke; Wood, Robin; Bekker, Linda-Gail

    2012-01-01

    Background The World Health Organization is currently developing guidelines on screening for tuberculosis disease to inform national screening strategies. This process is complicated by significant gaps in knowledge regarding mass screening. This study aimed to assess feasibility, uptake, yield, treatment outcomes, and costs of adding an active tuberculosis case-finding program to an existing mobile HIV testing service. Methods and Findings The study was conducted at a mobile HIV testing service operating in deprived communities in Cape Town, South Africa. All HIV-negative individuals with symptoms suggestive of tuberculosis, and all HIV-positive individuals regardless of symptoms were eligible for participation and referred for sputum induction. Samples were examined by microscopy and culture. Active tuberculosis case finding was conducted on 181 days at 58 different sites. Of the 6,309 adults who accessed the mobile clinic, 1,385 were eligible and 1,130 (81.6%) were enrolled. The prevalence of smear-positive tuberculosis was 2.2% (95% CI 1.1–4.0), 3.3% (95% CI 1.4–6.4), and 0.4% (95% CI 1.4 015–6.4) in HIV-negative individuals, individuals newly diagnosed with HIV, and known HIV, respectively. The corresponding prevalence of culture-positive tuberculosis was 5.3% (95% CI 3.5–7.7), 7.4% (95% CI 4.5–11.5), 4.3% (95% CI 2.3–7.4), respectively. Of the 56 new tuberculosis cases detected, 42 started tuberculosis treatment and 34 (81.0%) completed treatment. The cost of the intervention was US$1,117 per tuberculosis case detected and US$2,458 per tuberculosis case cured. The generalisability of the study is limited to similar settings with comparable levels of deprivation and TB and HIV prevalence. Conclusions Mobile active tuberculosis case finding in deprived populations with a high burden of HIV and tuberculosis is feasible, has a high uptake, yield, and treatment success. Further work is now required to examine cost-effectiveness and affordability and

  9. [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

  10. 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. PMID:26089621

  11. 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

  12. 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

  13. Biological evaluation of plants of Laos used in the treatment of tuberculosis in Lao traditional medicine

    PubMed Central

    Elkington, Bethany G.; Southavong, Bounhong; Sydara, Kongmany; Souliya, Onevilay; Vanthanouvong, Manoluck; Nettavong, Kongdeuane; Thammachack, Bounleuth; Pak, Dennis H.; Riley, Mary C.; Franzblau, Scott G.; Soejarto, D. Doel

    2010-01-01

    Tuberculosis has existed in Southeast Asia for thousands of years. Many traditional treatments involve herbal remedies. Over time, these traditional treatments have had the chance to become refined based on efficacy and safety. It was therefore hypothesized that plants that were used in the past and are still used today to treat symptoms associated with tuberculosis are more likely to contain anti-tubercular compounds than plants that have not been used continuously. To try to deduce which plants were used in Laos in the past, a collection of palm leaf manuscripts was studied and a list of plants used to treat symptoms associated with tuberculosis was compiled. Interviews were then conducted with contemporary healers to see if the same plants are still being used today. Plants that were found in the manuscripts and/or are presently used by healers were collected, extracted and were evaluated in an anti-tubercular assay. This paper presents the methods used to identify and collect plants used to treat symptoms indicative of tuberculosis, and the results of anti-TB assays to test for activity. PMID:21479105

  14. [Clinical practice guidelines from the Andalusian Society of Infectious Diseases (SAEI) for the treatment of tuberculosis].

    PubMed

    Domínguez-Castellano, Angel; Del Arco, Alfonso; Canueto-Quintero, Jesús; Rivero-Román, Antonio; Kindelán, José María; Creagh, Ricardo; Díez-García, Felipe

    2007-10-01

    The therapeutic scheme for initial pulmonary tuberculosis recommended by the SAEI is as follows: Initial phase, isoniazid, rifampin and pyrazinamide given daily for 2 months. In HIV(+) patients and immigrants from areas with a rate of primary resistance to isoniazid > 4%, ethambutol should be added until susceptibility studies are available. Second phase (continuation phase): rifampin and isoniazid, given daily or intermittently for 4 months in the general population. HIV(+) patients (< or = 200 CD4) and culture-positive patients after 2 months of treatment should receive a 7-month continuation phase. A 6-month regimen is recommended for extrapulmonary tuberculosis, with the exception of tuberculous meningitis, which should be treated for a minimum of 12 months and bone/joint tuberculosis, treated for a minimum of 9 months. Treatment regimens for multidrug resistant tuberculosis are based on expert opinion. These would include a combination of still-useful first-line drugs, injectable agents, and alternative agents, such as quinolones. Patients who present a special risk of transmitting the disease or of non-adherence should be treated with directly observed therapy. PMID:17915111

  15. 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

  16. Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment.

    PubMed

    Silva, João P; Gonçalves, Carine; Costa, César; Sousa, Jeremy; Silva-Gomes, Rita; Castro, António G; Pedrosa, Jorge; Appelberg, Rui; Gama, F Miguel

    2016-08-10

    Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi-drug standard therapies often results in treatment failure and emergence of multi-drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe the ability of the exogenous AMP LLKKK18 to efficiently kill mycobacteria. The peptide's potential was boosted by loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity and degradability, while potentiating peptide targeting to main sites of infection. The nanogels were effectively internalized by macrophages and the peptide presence and co-localization with mycobacteria within host cells was confirmed. This resulted in a significant reduction of the mycobacterial load in macrophages infected in vitro with the opportunistic M. avium or the pathogenic M. tuberculosis, an effect accompanied by lowered pro-inflammatory cytokine levels (IL-6 and TNF-α). Remarkably, intra-tracheal administration of peptide-loaded nanogels significantly reduced infection levels in mice infected with M. avium or M. tuberculosis, after just 5 or 10 every other day administrations. Considering the reported low probability of resistance acquisition, these findings suggest a great potential of LLKKK18-loaded nanogels for TB therapeutics. PMID:27261333

  17. Within-Host Heterogeneity of Mycobacterium tuberculosis Infection Is Associated With Poor Early Treatment Response: A Prospective Cohort Study.

    PubMed

    Cohen, Ted; Chindelevitch, Leonid; Misra, Reshma; Kempner, Maria E; Galea, Jerome; Moodley, Prashini; Wilson, Douglas

    2016-06-01

    The clinical management of tuberculosis is a major challenge in southern Africa. The prevalence of within-host genetically heterogeneous Mycobacterium tuberculosis infection and its effect on treatment response are not well understood. We enrolled 500 patients with tuberculosis in KwaZulu-Natal and followed them through 2 months of treatment. Using mycobacterial interspersed repetitive units-variable number of tandem repeats genotyping to identify mycobacterial heterogeneity, we report the prevalence and evaluate the association of heterogeneity with treatment response. Upon initiation of treatment, 21.1% of participants harbored a heterogeneous M. tuberculosis infection; such heterogeneity was independently associated with a nearly 2-fold higher odds of persistent culture positivity after 2 months of treatment (adjusted odds ratio, 1.90; 95% confidence interval, 1.03-3.50). PMID:26768249

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. When tuberculosis treatment fails. A social behavioral account of patient adherence.

    PubMed

    Sumartojo, E

    1993-05-01

    Several conclusions about measuring adherence can be drawn. Probably the best approach is to use multiple measures, including some combination of urine assays, pill counts, and detailed patient interviews. Careful monitoring of patient behavior early in the regimen will help predict whether adherence is likely to be a problem. Microelectronic devices in pill boxes or bottle caps have been used for measuring adherence among patients with tuberculosis, but their effectiveness has not been established. The use of these devices may be particularly troublesome for some groups such as the elderly, or precluded for those whose life styles might interfere with their use such as the homeless or migrant farm workers. Carefully designed patient interviews should be tested to determine whether they can be used to predict adherence. Probably the best predictor of adherence is the patient's previous history of adherence. However, adherence is not a personality trait, but a task-specific behavior. For example, someone who misses many doses of antituberculosis medication may successfully use prescribed eye drops or follow dietary recommendations. Providers need to monitor adherence to antituberculosis medications early in treatment in order to anticipate future problems and to ask patients about specific adherence tasks. Ongoing monitoring is essential for patients taking medicine for active tuberculosis. These patients typically feel well after a few weeks and either may believe that the drugs are no longer necessary or may forget to take medication because there are no longer physical cues of illness. Demographic factors, though easy to measure, do not predict adherence well. Tending to be surrogates for other causal factors, they are not amenable to interventions for behavior change. Placing emphasis on demographic characteristics may lead to discriminatory practices. Patients with social support networks have been more adherent in some studies, and patients who believe in the

  4. Gamma interferon release assay for monitoring of treatment response for active tuberculosis: an explosion in the spaghetti factory.

    PubMed

    Denkinger, Claudia M; Pai, Madhukar; Patel, Meena; Menzies, Dick

    2013-02-01

    Few studies have correlated the results of interferon (gamma interferon) release assays (IGRAs) with known markers of tuberculosis (TB) treatment response. We report the results of serial QuantiFERON-TB gold in-tube assay (QFT) testing on 149 patients with active tuberculosis and correlate the results with smear and culture conversion. We show that QFT results do not offer much value for treatment monitoring of TB disease. PMID:23175268

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Risk factors for treatment delay in pulmonary tuberculosis in Recife, Brazil

    PubMed Central

    dos Santos, Martinho APS; Albuquerque, Maria FPM; Ximenes, Ricardo AA; Lucena-Silva, Norma LCL; Braga, Cynthia; Campelo, Antônio RL; Dantas, Odimariles MS; Montarroyos, Ulisses R; Souza, Wayner V; Kawasaki, Alexandre M; Rodrigues, Laura C

    2005-01-01

    Background Tuberculosis is still a great challenge to public health in Brazil and worldwide. Early detection followed by effective therapy is extremely important in controlling the disease. Recent studies have investigated reasons for delays in treatment, but there is no agreed definition of what constitutes an "acceptable" delay. This study investigates factors associated with total delay in treatment of tuberculosis. Methods A cohort of adult cases of pulmonary tuberculosis diagnosed over a two-year period was studied. Patients were interviewed on entry, reporting the duration of symptoms before the start of treatment, and sputum and blood samples were collected. It was decided that sixty days was an acceptable total delay. Associations were investigated using univariable and multivariable analysis and the population attributable fraction was estimated. Results Of 1105 patients, 62% had a delay of longer than 60 days. Age, sex, alcoholism and difficulty of access were not associated with delays, but associations were found in the case of unemployment, having given up smoking, having lost weight and being treated in two of the six health districts. The proportion attributable to: not being an ex-smoker was 31%; unemployment, 18%; weight loss, 12%, and going to the two worst health districts, 25%. Conclusion In this urban area, delays seem to be related to unemployment and general attitudes towards health. Although they reflect the way health services are organized, delays are not associated with access to care. PMID:15777473

  14. [Management of TB suspected cases of drug resistant tuberculosis requiring a second treatment].

    PubMed

    Caminero, José A

    2004-06-01

    The management of patients with resistance to anti tuberculous drugs is complex and therefore must be managed by physician specialists. The most difficult patients are the cases in retreatment, where some very different possibilities are possible, as abandonment, failures and relapses. Patients with multi-drug resistant (MDR) tuberculosis are the most difficult to treat; MDR appears in all the failures or non-adherences to the treatment regime. To elaborate a scheme of retreatment for these patients, two guidelines must be followed: (1) do not rely on outcomes of drug susceptibility tests and (2) a detailed history of drug treatment must be considered of paramount importance. With this information, a retreatment scheme can be formulated that involves the use of at least three drugs not previously taken by the patient. For a successful control of tuberculosis, the national tuberculosis programs in Latin American countries must assure careful management of newly diagnosed patients. Secondly, if resources are available, a bank of second-line drugs must be ready for managing retreatment situations (e.g., 3 Z-Kn-Eth-Of/15 Z-Eth-Of) if first line drug treatments fail. Using individualized retreatment with second line drugs is recommended only in industrialized countries, and for a few middle income countries as a last resort. PMID:15495588

  15. 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

  16. The role of delamanid in the treatment of drug-resistant tuberculosis

    PubMed Central

    Lewis, Joseph M; Sloan, Derek J

    2015-01-01

    Tuberculosis (TB) remains a significant cause of death worldwide, and emergence of drug-resistant TB requires lengthy treatments with toxic drugs that are less effective than their first-line equivalents. New treatments are urgently needed. Delamanid, previously OPC-67863, is a novel drug of the dihydro-nitroimidazole class with potent anti-TB activity and great promise to be effective in the treatment of drug-resistant TB. This review examines the preclinical and clinical development of delamanid, reviews current guidance on its use and evaluates the opportunities and challenges for its future role in TB management. PMID:25999726

  17. Mycobacterium tuberculosis Lineage 7 Strains Are Associated with Prolonged Patient Delay in Seeking Treatment for Pulmonary Tuberculosis in Amhara Region, Ethiopia

    PubMed Central

    Norheim, Gunnstein; Namouchi, Amine; Zegeye, Ephrem D.; Kinander, Wibeke; Tønjum, Tone; Bekele, Shiferaw; Mannsåker, Turid; Bjune, Gunnar; Aseffa, Abraham; Holm-Hansen, Carol

    2015-01-01

    Recent genotyping studies of Mycobacterium tuberculosis in Ethiopia have reported the identification of a new phylogenetically distinct M. tuberculosis lineage, lineage 7. We therefore investigated the genetic diversity and association of specific M. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated from M. tuberculosis-positive sputum specimens (n = 240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned the M. tuberculosis genotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodern M. tuberculosis lineages, among which approximately 25% were not previously reported. Among the M. tuberculosis strains (n = 138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n = 60; 26.0%), the second largest to lineage 7 (n = 36; 15.6%), and the third largest to the lineage Haarlem (n = 35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test, P < 0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than other M. tuberculosis strains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and

  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. Tuberculosis incidence and treatment completion among Ugandan prison inmates

    PubMed Central

    Schwitters, A.; Kaggwa, M.; Omiel, P.; Nagadya, G.; Kisa, N.; Dalal, S.

    2016-01-01

    SUMMARY BACKGROUND The Uganda Prisons Service (UPS) is responsible for the health of approximately 32 500 inmates in 233 prisons. In 2008 a rapid UPS assessment estimated TB prevalence at 654/100 000, three times that of the general population (183/100 000). Although treatment programs exist, little is known about treatment completion in sub-Saharan African prisons. METHODS We conducted a retrospective study of Ugandan prisoners diagnosed with TB from June 2011 to November 2012. We analyzed TB diagnosis, TB-HIV comorbidity and treatment completion from national registers and tracked prison transfers and releases. RESULTS A total of 469 prisoners were diagnosed with TB over the 1.5-year period (incidence 955/100 000 person-years). Of 466 prisoners starting treatment, 48% completed treatment, 43% defaulted, 5% died and 4% were currently on treatment. During treatment, 12% of prisoners remaining in the same prison defaulted, 53% of transfers defaulted and 81% of those released were lost to follow-up. The odds of defaulting were 8.36 times greater among prisoners who were transferred during treatment. CONCLUSIONS TB incidence and treatment default are high among Ugandan prisoners. Strategies to improve treatment completion and prevent multidrug resistance could include avoiding transfer of TB patients, improving communications between prisons to ensure treatment follow-up after transfer and facilitating transfer to community clinics for released prisoners. PMID:24902552

  20. Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials.

    PubMed

    Moodley, Riya; Godec, Thomas R

    2016-03-01

    Multidrug-resistant (MDR) tuberculosis (TB) is a threat to global TB control, as suboptimal and poorly tolerated treatment options have resulted in largely unfavourable outcomes for these patients. The last of six cohort studies conducted in Bangladesh which assessed a new shorter regimen using currently available TB drugs showed promising results and offered the possibility of a more acceptable and more effective regimen than the one recommended by the World Health Organization (WHO). The aims of stage 1 of the STREAM (Evaluation of a Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) trial are to evaluate the efficacy and safety of this regimen, compared to the current WHO-recommended standard of care. Stage 2 evaluates two new bedaquiline-containing regimens: one an all-oral regimen and the second a further shortened and simplified version of the stage 1 study regimen, comparing the efficacy and safety of each to that of the stage 1 study regimen and also to the WHO-recommended standard of care. Success of the stage 1 study regimen would in all probability provide a new standard of care for MDR-TB patients, while positive results from the bedaquiline-containing regimens in stage 2 may allow for even greater progress in the management of this difficult population. PMID:26929418

  1. An Evaluation of Culture Results during Treatment for Tuberculosis as Surrogate Endpoints for Treatment Failure and Relapse

    PubMed Central

    Phillips, Patrick P. J.; Fielding, Katherine; Nunn, Andrew J.

    2013-01-01

    It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial. PMID:23667677

  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. PMID:27610260

  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 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

  6. Treatment of Active Pulmonary Tuberculosis in Adults: Current Standards and Recent Advances

    PubMed Central

    Hall, Ronald G.; Leff, Richard D.; Gumbo, Tawanda

    2010-01-01

    Tuberculosis is a global pandemic, with 9 million new cases of the disease and approximately 2 million deaths each year. More than 98% of patients treated for tuberculosis in the United States between 1993 and 2007 had drug-susceptible strains. The standard treatment regimen for drug-susceptible tuberculosis has not changed in decades and was developed on the basis of empiric observations of different treatment regimens. Only recently has the veracity of the scientific basis for standard therapy been examined. The backbone of therapy is still isoniazid, rifampin, and pyrazinamide, although fluoroquinolones are being investigated as a replacement for isoniazid. Recent population pharmacokinetic studies have demonstrated the importance of individualized dosing of isoniazid, pyrazinamide, and rifampin. Isoniazid serum clearance differs depending on the patient’s number of N-acetyltransferase 2 gene *4 (NAT2*4) alleles. Pyrazinamide serum clearance has been shown to increase with increases in body weight. Rifampin’s volume of distribution, clearance, and absorption have wide between-patient and within-patient variability. Microbial pharmacokinetic-pharmacodynamic (PK-PD) indexes and targets to optimize microbial killing and minimize resistance have been identified for rifampin, isoniazid, pyrazinamide, and the fluoroquinolones. These PK-PD indexes suggest that different doses and dosing schedules than those currently recommended could optimize therapy and perhaps shorten duration of therapy. Efflux pump inhibition is also being investigated to enhance first-line antituberculosis drug therapy. Comorbid conditions such as diabetes mellitus and genetically determined iron overload syndromes have been associated with significantly worse patient outcomes. Therapy for these and other patient groups needs further improvement. These patient factors, the covariates for pharmacokinetic variability, and PK-PD factors suggest the need to individualize therapy for patients with

  7. 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. PMID:25795541

  8. Clinical research in the treatment of tuberculosis: current status and future prospects.

    PubMed

    Chang, K-C; Yew, W-W; Sotgiu, G

    2015-12-01

    To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens. Our review was restricted to Phase II/III clinical trials, cohort and case-control studies, and systematic reviews of clinical studies. TB programmatic and patient behavioural factors, non-TB drugs, adjunctive surgery, new vaccines, immunotherapy, antiretroviral therapy and management of latent tuberculous infection are outside the scope of this review. An algorithm was used to systematically search PubMed for relevant articles published in English from 1 January 2005 to 31 December 2014. Articles without evaluated factors (drugs, dosing factors and regimens) or comparative analysis of specified anti-tuberculosis treatment outcomes were excluded. Of the 399 articles initially identified, 294 were excluded. The main findings of the remaining 105 articles are described under two categories: presumed drug-susceptible TB and MDR-TB. Fifty-nine articles included under drug-susceptible TB were divided into 12 subcategories: isoniazid, rifampicin, pyrazinamide, fluoroquinolones, fixed-dose combination drugs, dosing frequency, treatment phases, treatment duration, experimental regimens for pulmonary (surrogate markers vs. clinical outcomes) and extra-pulmonary TB. Forty-nine articles included under MDR-TB were divided into seven subcategories: fluoroquinolones, pyrazinamide, second-line injectable drugs, World Health Organization Group 4 and Group 5 drugs, MDR-TB regimens and novel drugs. Clinical research in the last decade and ongoing trials might furnish new paradigms for improving the treatment of this recalcitrant ancient disease. PMID:26614181

  9. [Tuberculosis control of urban areas in Japan].

    PubMed

    2000-10-01

    The rates of tuberculosis remain high in urban areas. The declining speed of tuberculosis incidence rate in urban areas has been slower than other areas. Efforts and resources to tuberculosis control must be concentrated on urban locations to eradicate tuberculosis in Japan. 1. Tuberculosis control in a public health center of urban area: Teru OGURA and Chiyo INOGUCHI (Toshima City, Ikebukuro Public Health Center, Tokyo Metropolitan) A wide range of TB control measures is implemented by public health centers, such as a patient registration, home-visit guidance, contact examination in urban areas. Directors of every health center have the direct responsibility for tuberculosis control measures in their jurisdiction. Ikebukuro is urban areas where there are many offices, shopping and amusement facilities. Urban people is often on the move looking for job, so public health centers are often not easy to carry out contact examinations as planned. In recent years, homelessness has been recognized as a growing urban social problem. Their incidence of tuberculosis is high. Special TB control program must be carried out in urban areas. 2. Tuberculosis Control in Tokyo Metropolitan: Kazumasa MATSUKI (Department of Infectious Diseases and Tuberculosis, Bureau of Public Health, Tokyo Metropolitan) There has been a steady decline in the TB wards. The beds for TB patients are running short and even smear positive TB cases cannot be put in a hospital without waiting several days. Staffs of an urban emergency department must protect tuberculosis infection by environmental controls of emergency room. Tokyo Metropolitan government supports the engineering improvements of emergency room to hospitals. Directly observed therapy for tuberculosis patients at a district has been implemented to complete their therapy. On DOT, a trained health worker observes the patient take anti-TB medication. 3. Usefulness of Molecular Epidemiologic approach on Tuberculosis Control: Atsushi HASE (Osaka

  10. Tuberculosis treatment outcomes among hospital workers at a public teaching and national referral hospital in Kenya

    PubMed Central

    Makori, L.; Gikera, M.; Wafula, J.; Chakaya, J.; Edginton, M. E.; Kumar, A. M. V.

    2013-01-01

    Setting: Kenyatta National Hospital (KNH), Nairobi, Ken-ya, a large referral and teaching hospital. Objective: 1) To document tuberculosis (TB) case notification rates and trends; 2) to describe demographic, clinical and workplace characteristics and treatment outcomes; and 3) to examine associations between demographic and clinical characteristics, HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome) treatment and anti-tuberculosis treatment outcomes among hospital workers with TB at KNH during the period 2006–2011. Design: A retrospective cohort study involving a review of medical records. Results: The TB case notification rate among hospital staff ranged between 413 and 901 per 100 000 staff members per year; 51% of all cases were extra-pulmonary TB; 74% of all cases were among medical, paramedical and support staff. The TB-HIV coinfection rate was 60%. Only 75% had a successful treatment outcome. Patients in the retreatment category, those with unknown HIV status and those who were support staff had a higher risk of poor treatment outcomes. Conclusion: The TB case rate among hospital workers was unacceptably high compared to that of the general population, and treatment outcomes were poor. Infection control in the hospital and management of staff with TB requires urgent attention. PMID:26393055