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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 Central

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

    2016-01-01

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

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

    PubMed

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

    2016-08-01

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

  4. 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. 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

  20. 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

  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 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

  3. 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

  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. 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

  17. 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

  18. 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

  19. 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

  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

    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

  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 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

  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. 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

  16. 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

  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. 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

  2. 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

  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. 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

  2. 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

  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

    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

  17. 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

  18. 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

  19. 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

  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. 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

  13. 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

  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. 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

  2. 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

  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 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

  3. 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

  4. 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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. 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

  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

  11. Impact of Latent Infection Treatment in Indigenous Populations

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-02-01

    This document describes the recommendations of a group of scientific societies concerning the first-line therapeutic approach to paediatric tuberculosis (TB). The treatment of pulmonary TB should be based on the existence of parenchymal involvement and the risk of antibiotic resistance. The treatment of extra-pulmonary TB is based on the regimens used for severe pulmonary TB. The administration of corticosteroids is recommended only in cases of miliary TB, tuberculous meningitis and tuberculous pericarditis. Vitamin B6 may be indicated in the case of isoniazid-treated TB in breastfeeding infants, severely malnourished subjects, or patients with other diseases at high risk of vitamin deficiency. Once having started treatment, children with TB should be carefully followed up in order to evaluate compliance, the response to treatment, the need for treatment changes, and the presence of drug-related adverse events. Primary care paediatricians can support reference centres in providing family healthcare education and encouraging treatment compliance. PMID:26612773

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Health System Delay among the Pulmonary Tuberculosis Patients Presenting in the DOTS Centers of Nepal

    PubMed Central

    Mahato, Roshan Kumar; Koju, Rajendra

    2016-01-01

    Introduction Health system delay is the time for complete diagnosis of the disease after patient approaches a health care provider. Aim The study aims to identify the characteristics and the determinants of unacceptable health system delay (≥ 7 days delay from health system) in diagnosis of new pulmonary tuberculosis patients attending in Direct Observation Treatment Short course (DOTS) centers of Nepal. Materials and Methods An analytical cross-sectional study was conducted by administrating a structured questionnaire interview and reviewing the medical record of the new sputum smear positive pulmonary tuberculosis cases during January–May 2015. The generalized linear model (GLM) was applied to control the clustering effects. Multiple logistic regressions were performed to identify the association between variables with ≥ 7 days of unacceptable health system delay. Results Of the 374 new sputum smear positive pulmonary tuberculosis cases, the factors that were associated with unacceptable health system delay (time ≥ 7 days) were doing business (adj.OR= 1.61, 95% CI: 1.22-2.11; p-value <0.001) and unemployed (adj.OR= 3.04, 95% CI: 1.53-6.04; p-value <0.001) had chances of health system delay. However, getting support from parents (adj.OR= 0.55, 95% CI: 0.44-0.68; p-value <0.001), consultation with the private practitioners/ pharmacists (adj.OR= 0.24, 95% CI: 0.07-0.81; p-value 0.021), visiting government health facilities (adj.OR= 0.31, 95% CI: 0.13-0.73; p-value 0.008), using X-ray (adj.OR= 0.69, 95% CI: 0.49-0.97; p-value 0.032) and advance technologies for diagnosis of TB (adj.OR= 0.60, 95% CI: 0.39-0.94; p-value 0.024) were found contributing to reduce health system delay while controlling socio-economic, knowledge, presence of symptoms and attitude factors. Conclusion About a quarter of new TB patients faced health system delay problems. Socioeconomic factors, unemployment, influences the health system delay when controlled for other covariates. PMID

  16. Effect of standard tuberculosis treatment on naive, memory and regulatory T-cell homeostasis in tuberculosis-diabetes co-morbidity.

    PubMed

    Kumar, Nathella P; Moideen, Kadar; Viswanathan, Vijay; Kornfeld, Hardy; Babu, Subash

    2016-09-01

    Perturbations in CD4(+) and CD8(+) T-cell phenotype and function are hallmarks of tuberculosis-diabetes co-morbidity. However, their contribution to the pathogenesis of this co-morbidity and the effect of anti-tuberculosis treatment on the phenotype of the T-cell subsets is poorly understood. In this study, we examined the frequency of different T-cell subsets in individuals with pulmonary tuberculosis (PTB) with diabetes mellitus (DM) or without coincident diabetes mellitus (NDM) before, during and after completion of anti-tuberculosis chemotherapy. PTB-DM is characterized by heightened frequencies of central memory CD4(+) and CD8(+) T cells and diminished frequencies of naive, effector memory and/or effector CD4(+) and CD8(+) T cells at baseline and after 2 months of treatment but not following treatment completion in comparison with PTB-NDM. Central memory CD4(+) and CD8(+) T-cell frequencies exhibited a positive correlation with fasting blood glucose and glycated haemoglobin A1c levels, whereas the frequencies of naive and effector memory or effector CD4(+) and CD8(+) T cells exhibited a negative correlation. However, the frequencies of CD4(+) and CD8(+) T-cell subsets in individuals with PTB exhibited no significant relationship with bacterial burdens. Finally, although minor alterations in the T-cell subset compartment were observed at 2 months of treatment, significantly decreased frequencies of central memory and significantly enhanced frequencies of naive CD4(+) and CD8(+) T cells were observed at the completion of treatment. Our data reveal a profound effect of coexistent diabetes on the altered frequencies of central memory, effector memory and naive T cells and its normalization following therapy. PMID:27289086

  17. In Silico-Based High-Throughput Screen for Discovery of Novel Combinations for Tuberculosis Treatment

    PubMed Central

    Singh, Ragini; Ramachandran, Vasanthi; Shandil, Radha; Sharma, Sreevalli; Khandelwal, Swati; Karmarkar, Malancha; Kumar, Naveen; Solapure, Suresh; Saralaya, Ramanatha; Nanduri, Robert; Panduga, Vijender; Reddy, Jitendar; Prabhakar, K. R.; Rajagopalan, Swaminathan; Rao, Narasimha; Narayanan, Shridhar; Anandkumar, Anand; Datta, Santanu

    2015-01-01

    There are currently 18 drug classes for the treatment of tuberculosis, including those in the development pipeline. An in silico simulation enabled combing the innumerably large search space to derive multidrug combinations. Through the use of ordinary differential equations (ODE), we constructed an in silico kinetic platform in which the major metabolic pathways in Mycobacterium tuberculosis and the mechanisms of the antituberculosis drugs were integrated into a virtual proteome. The optimized model was used to evaluate 816 triplets from the set of 18 drugs. The experimentally derived cumulative fractional inhibitory concentration (∑FIC) value was within twofold of the model prediction. Bacterial enumeration revealed that a significant number of combinations that were synergistic for growth inhibition were also synergistic for bactericidal effect. The in silico-based screen provided new starting points for testing in a mouse model of tuberculosis, in which two novel triplets and five novel quartets were significantly superior to the reference drug triplet of isoniazid, rifampin, and ethambutol (HRE) or the quartet of HRE plus pyrazinamide (HREZ). PMID:26149995

  18. Features of Adolescents Tuberculosis at a Referral TB’s Hospital in Tehran, Iran

    PubMed Central

    Lotfian, Ferial; Bolursaz, Mohammad Reza; Khalilzadeh, Soheila; Baghaie, Noshin; Hassanzad, Maryam; Velayati, Aliakbar

    2016-01-01

    Objective To identify the pattern of the clinical, radiological, diagnostic procedures and loss to follow-up of the diagnosed cases of active tuberculosis (TB) adolescents. Methods This study was a retrospective analysis of the medical records of 143 adolescents aged 10 to 18 years with tuberculosis who were admitted TB wards of National Research Institute of Tuberculosis and Lung Disease (NRITLD) in Tehran, Iran, between March 2006 and March 2011. Results Of the 143 patients identified, 62.9% were females. Median age of the patients was 16 years. The contact source was identified in 47.5%. The most common presenting symptom was cough (86%). Isolated pulmonary TB (PTB) was detected in 113 patients (79%), 21 patients (14.7%) had extrapulmonary TB(EPTB), and 9 patients (6.3%) had PTB and EPTB. The most common site of EPTB was pleural (14%). The most common radiographic finding was infiltration (61%). Positive acid fast smears were seen in 67.6%. Positive cultures for Mycobacterium tuberculosis (M. TB) were seen in 44.7%. Positive Polymerase chain reaction (PCR) results were seen in 60%. The adolescents aged 15 to 18 years were more likely to lose weight (p=0.001), smear positive (p=0.001), culture positive (p<0.001) and have positive PCR results (p=0.009). The type of TB (p=0.017) was a significant factor influencing loss to follow-up. Conclusions The study has revealed that the clinical and radiological findings of TB in adolescents are combination as identified in children and adults. The TB control programs should pay more attention to prevention and treatment of TB in adolescents. PMID:26740866

  19. [Reconsideration of the admission and discharge criteria of tuberculosis patients in Japan].

    PubMed

    Masuyama, Hidenori; Igari, Hidetoshi

    2013-03-01

    public in September 2007. This modified notice brought in a prolonged period of hospitalization and created confusion in clinical practice. Based on the result of our study for infectiousness, it is appropriate to use the guideline in January 2005. 3. Consideration of the standard for leaving TB hospital: Masako WADA (Chemotherapy Research Institute, Kaken Hospital) In Japan, infectious pulmonary tuberculosis patients are ordered to receive chemotherapy in admission to tuberculosis treatment facilities according to Infectious Diseases Control Law. Infectious pulmonary tuberculosis is defined as sputum smear positive for acid-fast bacilli (AFB) even it is questionable. And there consecutive negative sputum smear for AFB is needed as a criteria for discharge. In this study we defined our own admission criteria as follows, medical service is needs owing to serious pulmonary tuberculosis, meningitis and other complications. We simulated the cost for hospitalization. During study period 170 patients were admitted and only 36 patients (21%) were needed hospitalization on our own criteria. The other 134 patients were admitted because of infectiousness. The average hospital stay was 63.0 days and 64.8 days, respectively. Total cost of patients cares were 26 million yen and 100 million yen respectively. On the points of saving medical costs, Infectious Diseases Control Law should be revised. 4. Recent problems in tuberculosis hospitalization and countermeasures related to patients support in urban area: Michihiko YOSHIDA (Infectious Control Section, Health and Safety Division, Bureau of Social Welfare and Public Health, Tokyo Metropolitan Govenment) Standard treatment for tuberculosis led to a shortening of hospitalization days. After discharge most patients are treated as outpatient. In the outpatient, the decreased numbers and the bias in the geographical distribution of tuberculosis hospitals impair patients' accessibility and may lead to increase of drop out cases. And there

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Volmink, J; Garner, P

    1997-11-29

    A literature review was conducted to assess the effectiveness of strategies promoting adherence to treatment for tuberculosis (TB). Five studies met the inclusion criteria of being randomized or pseudorandomized controlled trials of interventions to promote adherence with curative or preventive treatment for TB, with at least one measure of adherence. The relative risk for tested reminder cards sent to patients who defaulted upon treatment was 1.2, 1.4 for help given to patients by lay health workers, 1.6 for monetary incentives offered to patients, 1.2 for health education, 2.4 or 1.1 for a combination of a patient incentive and health education, and 1.2 for intensive supervision of staff to TB clinics. No completed trial of directly observed treatment was included in the review. All of the interventions tested improved adherence, but it remains unclear whether health education alone leads to better adherence to treatment. PMID:9418086

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

    PubMed

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

    2014-12-01

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

  3. Evaluation of factors associated with failure of tuberculosis treatment under DOTS in northern Islamic Republic of Iran.

    PubMed

    Mohammadzadeh, Kh Ali; Ghayoomi, A; Maghsoudloo, D

    2016-02-01

    Tuberculosis treatment failure remains a major health problem in many parts of the Islamic Republic of Iran. This study was conducted to identify the risk factors associated with failure of tuberculosis treatment under the DOTS strategy in two cities of Golestan province. A retrospective cohort study in 2012-2013 was conducted on 167 smearpositive tuberculosis patients monitored under DOTS. Demographic, clinical and treatment outcome factors and social determinants of health were recorded for each patient. Multivariate regression analysis found that the strongest predictors of tuberculosis treatment failure were: being infected with other diseases (OR 9.35; 95% CI: 3.01-29.1), male sex (OR 5.03; 95% CI: 1.58-16.1), Turkoman ethnicity (OR 11.0; 95% CI: 2.00-60.1), family history of tuberculosis (OR 0.21; 95% CI: 0.05-0.96) and household size (OR 1.21; 95% CI: 0.99-1.48). Recommendations include better follow-up for patients with other diseases and facilitating access to treatment, especially for Turkoman patients. PMID:27180736

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

    PubMed

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

    2015-05-01

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

  5. [Nursing of tuberculosis patients--quality nursing to support patient's compliance to treatment].

    PubMed

    Nasu, Ayako; Kobayashi, Noriko

    2004-12-01

    Tuberculosis control program in Japan focuses more on completion of treatment. The activities for patients to complete treatment are being actively done with collaboration between nurses of hospitals and public health nurses of the health centers. In 2000, Ministry of Health Welfare announced DOTS program version Japan. As a result, health centers of big cities implemented DOTS for homeless tuberculosis patients and hospitals DOT for in-patients. In 2003, the government demonstrated the scheme of DOTS strategy Expansion Program version Japan, which includes community DOTS types to be selected depend upon the risk of default with an individual patient. It is necessary to develop and utilize social and human resources in the community to expand surely supporting system for patient's compliance. Mutual understanding and collaboration of the relevant organizations become very important. In this symposium, four panels from hospital, clinic and public health center discuss on the current situation and challenge of supporting system and the assessment of treatment outcome. 1. DOTS implementation with collaboration on nursing activities between hospital and public health center in Kyoto Prefecture: Ikuyo HIROHATA (National Hospital Organization Minami Kyoto National Hospital). 2. From standpoint of clinical practice: Hidenori MASUYAMA (Japan Anti-Tuberculosis Association Shibuya Clinic). 3. The activities for case support based on DOTS Program in Wakayama Prefecture: Kimiko KAWASAKI (Tanabe Public Health Center, Wakayama Prefecture). 4. Assessment of supporting activities for patient's compliance: Tomoko TAKANO (Uki Public Health Center, Kumamoto Prefecture). Three speakers gave additional comments and advice on quality supporting and nursing activities for patient's compliance through good coordination between hospitals and publics health centers. PMID:15782620

  6. Pattern of drug resistance of Mycobacterium tuberculosis clinical isolates to first-line antituberculosis drugs in pulmonary cases

    PubMed Central

    Kalo, Deepika; Kant, Surya; Srivastava, Kanchan; Sharma, Ajay K.

    2015-01-01

    Context: Mycobacterium tuberculosis (MTB), the human pathogen causes Tuberculosis (TB). It is a highly infectious and globally pandemic disease. The severity increases when the MTB becomes resistant to antituberculosis drugs. India is reported to be in the second place, with the highest number of drug-resistant TB cases. The treatment of drug-resistant TB is even more complicated. Materials and Methods: The present study comprises of 159 TB patients, in which 88 are reported to have drug-resistant TB (55.3%). All the patients are in the age group of 18–70 years. Patients having extrapulmonary TB and diabetes were excluded from the study. The collected samples were processed and stained for acid fastness and smear positivity. They were subjected to inoculation on Lowenstein–Jensen (LJ) slants. Results: The results showed that out of the four drugs — Streptomycin, Isoniazid, Rifampicin, and Ethambutol — the resistant cases reported in Streptomycin were 45 (24.9%), whereas, in Isoniazid, Rifampicin, and Ethambutol, the resistant cases were 62 (34.2%), 27 (14.9%), and 47 (26.0%), respectively. Isoniazid showed the highest percentage of resistance among the patients. Conclusion: Effective measures such as convincing the patients to take the prescribed drugs and follow the five major strategies under the Directly Observed Treatment, Short Course (DOTS), could help in managing such cases. PMID:26180382

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

    PubMed

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

    2016-07-01

    Treatment guidance for non-multidrug-resistant (MDR) rifampicin-resistant (RMP-R) tuberculosis (TB) is variable. We aimed to undertake a systematic review and meta-analysis of the randomised controlled trial (RCT) data behind such guidelines to identify the most efficacious treatment regimens. Ovid MEDLINE, the Web of Science and EMBASE were mined using search terms for TB, drug therapy and RCTs. Despite 12 604 records being retrieved, only three studies reported treatment outcomes by regimen for patients with non-MDR RMP-R disease, preventing meta-analysis. Our systematic review highlights a substantial gap in the literature regarding evidence-based treatment regimens for RMP-R TB. PMID:27287636

  8. Poor response to tuberculosis treatment with regimens without rifampicin in immunosuppressed AIDS patients.

    PubMed

    O'Donnel, M M; Souza Carvalho, S; Gadelha, A J; Morgado, M G; Galhardo, M C G; Lourenço, M C; Rolla, V C

    2002-12-01

    A prospective study was conducted on 79 advanced immunosuppressed AIDS patients from 1997 to 1999, during which nine cases of tuberculosis (TB) were diagnosed. The main clinical and laboratory characteristics and the response to TB treatment were reviewed. The clinical manifestations of TB were: pulmonary (six cases), extrapulmonary (two cases) and disseminated (one case). These patients were being treated with highly active antiretroviral treatment (HAART) and were not responding. In three cases an optional regimen without rifampicin (RMP) was indicated to maintain HAART during TB treatment. A clinical response to TB treatment (disappearance of fever) was observed in 6/9 patients during a mean of 73 days (SD = 96). The three unresponsive patients were those treated without RMP. A switch to TB regimens containing RMP was proposed and successful. In our study, though it was limited by a small sample size, the response to TB regimens without rifampin was poor in immunosupressed patients failing HAART. PMID:12585969

  9. Characteristics and Treatment Outcomes of “Transfer-Out” Pulmonary Tuberculosis Patients in Gondar, Ethiopia

    PubMed Central

    Belayneh, Tadesse; Kassu, Afework; Tigabu, Desalgne; Asmare, Gashaw; Tilaye, Sofanit; Klinkenberg, Eveline

    2016-01-01

    Background. During tuberculosis treatment, patients may transfer to continue treatment at another health facility. To ensure adherence until treatment completion, keeping track of patients is paramount. This study aimed to investigate treatment outcomes of patients who transferred out from the University of Gondar Hospital. Methods. This was a retrospective cohort evaluation of patients registered from 2009 to 2013. Treatment outcomes were collected from the TB registers of receiving units using a standardized data capture format. Results. During the study period 3,707 patients initiated treatment and 47.5% (1,760) transferred out. The study evaluated the outcome of 26% (457/1,760) patients, of whom 403 (88%) arrived in the receiving units. Overall, 79% were successfully treated and 13.8% transferred out for a second time. For all transferred-out cases, treatment outcomes were not reported to the referring unit. Conclusion and Recommendation. About half of the patients were transferred out to complete treatment elsewhere. Although successful treatment outcome was obtained in 79% of patients, these results were not fed back to the referring unit. Implementing a clear mechanism to communicate the arrival of and treatment outcome for transfer-out patients and appropriate patient education on treatment unit selection before treatment and during transfer-out are recommended. PMID:27313887

  10. Post-treatment change in Mycobacterium tuberculosis antigen-stimulated tumor necrosis factor-alpha release in patients with active tuberculosis

    PubMed Central

    Kim, Chang Ho; Yoo, Seung Soo; Lee, Shin Yup; Cha, Seung Ick; Park, Jae Yong

    2015-01-01

    Background Monitoring tuberculosis (TB) treatment response remains challenging due to lack of reliable laboratory markers. In recent years, increased efforts have been exerted toward development of new biomarkers reflecting treatment response appropriately. While performance of interferon-gamma release assays (IGRAs) to monitor anti-TB treatment has been extensively evaluated, there is no data about post-treatment changes in Mycobacterium tuberculosis (MTB) antigen-stimulated tumor necrosis factor-alpha (TNF-α) release in active TB patients. Herein, we explored whether the MTB antigen-stimulated TNF-α release would be useful for monitoring responses to anti-TB treatment. Methods We compared unstimulated (TNF-αNil), MTB antigen-stimulated (TNF-αAg), and MTB antigen-stimulated minus unstimulated TNF-α levels (TNF-αAg-Nil) in supernatants from QuantiFERON-TB Gold In-Tube tests before and after treatment in 16 active TB patients, 25 latent TB infection (LTBI) subjects, and 10 healthy controls (HC). Results TNF-αAg and TNF-αAg-Nil levels decreased significantly after treatment in patients with active TB. In addition, TNF-αNil, TNF-αAg, and TNF-αAg-Nil levels were significantly higher in untreated active TB patients compared to LTBI subjects and HC. Conclusions This finding cautiously suggests that MTB Ag-stimulated TNF-α response may be a potential adjunctive marker for monitoring treatment response in active TB patients. PMID:26101647

  11. Prevalence and treatment outcome of pulmonary and extrapulmonary pediatric tuberculosis in southwestern Iran

    PubMed Central

    Alavi, Seyed Mohammad; Salmanzadeh, Shokrollah; Bakhtiyariniya, Pejman; Albagi, Ali; Hemmatnia, Fatemeh; Alavi, Leila

    2015-01-01

    Background: Knowledge about childhood tuberculosis (TB) in Iran is limited. This study aimed to determine the proportion of tuberculosis in children living in Khuzestan in southwest of Iran and its treatment outcomes. Methods: In this retrospective study, the child’s medical records registered in national TB program (NTP) unit of Khuzestan Health Center (KHC) for TB treatment from 2005 to 2010 were studied. Data including demographic, clinical presentation, laboratory test results, and treatment outcomes were extracted from the files and were analyzed. Results: Of total 4104 new TB cases registered in KHC, 203 (4.9%) were children. The mean age was 10.7±4.3 years, and 75.7% of them were females. More than 84% of TB children cases were 10 years or older, whereas, young children (< 5 years old) accounted for 5.6%. Of the total studied cases, 57.1% were pulmonary TB and 42.9% were extra pulmonary, 91.7% were successfully treated and 8.3% had poor treatment outcome. The main risk factors for poor treatment outcome were: age <5 years (OR: 0.17, 95% CI, 0.04-0.76), low body weight (OR: 0.08, 95% CI, 0.01-0.60), household contact with cases of TB treatment failure (OR: 0.13, 95% CI, 0.03-0.52), and exposure to cigarette smoke odor inside the home (OR: 0.17, 95% CI, 0.05-0.56). Conclusion: The proportion of pediatric TB in the region was lower than expected. The treatment success rate was higher than the rate defined in NTP. Special attention should be given to children aged less than five years, low body weight, contact with TB treatment failure cases, and exposure to cigarette smoke. PMID:26644895

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed

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

    2013-12-01

    This is a retrospective study conducted from January 2008 to December 2010 on sectional descriptive analysis of records of patients treated for MDR-TB and whose follow-up was in the thoracic department of Centre Hospitalier Universitaire (CHU) of Cocody in Abidjan Côte d'Ivoire. We selected eight patients who met the inclusion criteria of 21 MDR-TB patients registered during the study period. The average age was 29.25years ranging from 21 to 39. Males accounted for 75% of the patients (6 males and 2 females). The students represented the professional social layer most affected with 37.5% of the patients. All patients had a history of tuberculosis and only one patient was HIV positive under anti-retroviral (zidovudin, lamivudin and efavirenz). All cultures found Mycobacterium tuberculosis. The resistance profile in addition to isoniazid and rifampicin, found two cases of resistance to ethambutol and streptomycin. The chest radiograph at the time of initiation of second-line treatment showed essentially excavations in 75% of cases and infiltrates in 25%. The lesions were bilateral in 7 of 8 patients (87.5%). The main side effects observed during treatment were limited to cochleovestibular disorders (2 patients) and neuropsychiatric disorders (2 patients) and digestive disorders in half of the patients with removal of the offending molecule kanamycin. After 24months of treatment, it was numbered five cures (62.5%), two failures and one death. PMID:24183291

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

    PubMed Central

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

    2013-01-01

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

  15. Does Concurrent Use of Some Botanicals Interfere with Treatment of Tuberculosis?

    PubMed

    Folk, William R; Smith, Aaron; Song, Hailong; Chuang, Dennis; Cheng, Jianlin; Gu, Zezong; Sun, Grace

    2016-09-01

    Millions of individuals with active TB do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. Many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for prophylaxis and treatment of TB, as suggested by results of a recent clinical trial of the South African botanical Sutherlandia frutescens (L.) R. Br. (Sutherlandia). Here we provide a brief summary of Sutherlandia's effects upon rodent microglia and neurons relevant to tuberculosis of the central nervous system (CNS-TB). We have observed that ethanolic extracts of Sutherlandia suppress production of reactive oxygen species (ROS) in rat primary cortical neurons stimulated by NMDA and also suppress LPS- and interferon γ (IFNγ)-induced ROS and nitric oxide (NO) production by microglial cells. Sutherlandia consumption mitigates microglial activation in the hippocampus and striatum of ischemic brains of mice. RNAseq analysis indicates that Sutherlandia suppresses gene expression of oxidative stress, inflammatory signaling and toll-like receptor pathways that can reduce the host's immune response to infection and reactivation of latent Mycobacterium tuberculosis. As a precautionary measure, we recommend that individuals receiving isoniazid for pulmonary or cerebral TB, be advised not to concurrently use botanicals or dietary supplements having antioxidant activity. PMID:27155670

  16. [A clinical study on tuberculosis among young adults in Japan: analysis on patients admitted to national hospitals in Kanto- and Kinki-areas in the year 2000].

    PubMed

    Yotsumoto, Hideki; Yonemaru, Makoto; Suzuki, Katsuhiro; Kawabe, Yoshiko; Sasaki, Yuka; Toyoda, Emiko; Yamagishi, Fumio; Kudoh, Koichiro; Kurasawa, Takuya; Ito, Masami; Kawashiro, Takeo; Sakatani, Mitsunori; Mori, Masashi

    2003-08-01

    Considering the high social activity, the trend of tuberculosis among young adults appears to be one of the key factors that influence the future morbidity rate of tuberculosis in Japan. To investigate its current characteristics, we analyzed new cases of tuberculosis aged 20 to 29 who were admitted to 7 national hospitals in Kanto- and Kinki-areas during the period of January 1st to December 31st, 2000. Data on the following items were compiled: sex, age, body height and weight, nationality; background factors such as life style, complications; course of the disease before the diagnosis; result of PPD skin test; severity of the disease estimated by the amount of M. tuberculosis in sputum and the grade of chest X-ray findings; therapeutic regimens and the response rate. Data were collected from 234 patients (129 males and 105 females) and the results were as follows: 1) about 80% of the patients were symptomatic and in 50% of patients who presented with cough, more than one month was needed before establishing the diagnosis as TB, 2) the disease was found in advanced stage in more than half of the patients, 3) foreigner patients, most of them were from Kanto-area, accounted for 11%, and were in advanced stage, some with drug-resistant tuberculosis, 4) INH resistance was noted in 7.7%, 5) pyrazinamide was included in the therapeutic regimens in 84.0% of the smear positive patients, 6) the admission period was within 90 days in 63.7% of the patients, however, the duration of treatment was 6 months in only 48.0% of patients who were treated with regimens containing pyrazinamide. More efforts for early detection of patients is needed to prevent the transmission of the disease, and more extensive use of directly observed therapy is essential for the prevention of dropout. We also argued about the shortening of the admission and duration of treatment in these patients. PMID:14509224

  17. Predicting tuberculosis among migrant groups.

    PubMed

    Watkins, R E; Plant, A J

    2002-12-01

    In industrialized countries migrants remain a high-risk group for tuberculosis (TB). Multiple linear regression analysis was used to determine the ability of indicators of TB incidence in the country of birth to predict the incidence of TB among migrants in Australia during 1997. World Health Organization total case notifications, new smear-positive case notifications and the estimated incidence of TB by country of birth explained 55, 69 and 87% of the variance in TB incidence in Australia, respectively. Gross national income of the country of birth and unemployment level in Australia were also significant predictors of TB in migrant groups. Indicators of the incidence of TB in the country of birth are the most important group-level predictors of the rate of TB among migrants in Australia. PMID:12558347

  18. Clinical application of whole-genome sequencing to inform treatment for multidrug-resistant tuberculosis cases.

    PubMed

    Witney, Adam A; Gould, Katherine A; Arnold, Amber; Coleman, David; Delgado, Rachel; Dhillon, Jasvir; Pond, Marcus J; Pope, Cassie F; Planche, Tim D; Stoker, Neil G; Cosgrove, Catherine A; Butcher, Philip D; Harrison, Thomas S; Hinds, Jason

    2015-05-01

    The treatment of drug-resistant tuberculosis cases is challenging, as drug options are limited, and the existing diagnostics are inadequate. Whole-genome sequencing (WGS) has been used in a clinical setting to investigate six cases of suspected extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) encountered at a London teaching hospital between 2008 and 2014. Sixteen isolates from six suspected XDR-TB cases were sequenced; five cases were analyzed in a clinically relevant time frame, with one case sequenced retrospectively. WGS identified mutations in the M. tuberculosis genes associated with antibiotic resistance that are likely to be responsible for the phenotypic resistance. Thus, an evidence base was developed to inform the clinical decisions made around antibiotic treatment over prolonged periods. All strains in this study belonged to the East Asian (Beijing) lineage, and the strain relatedness was consistent with the expectations from the case histories, confirming one contact transmission event. We demonstrate that WGS data can be produced in a clinically relevant time scale some weeks before drug sensitivity testing (DST) data are available, and they actively help clinical decision-making through the assessment of whether an isolate (i) has a particular resistance mutation where there are absent or contradictory DST results, (ii) has no further resistance markers and therefore is unlikely to be XDR, or (iii) is identical to an isolate of known resistance (i.e., a likely transmission event). A small number of discrepancies between the genotypic predictions and phenotypic DST results are discussed in the wider context of the interpretation and reporting of WGS results. PMID:25673793

  19. Previous treatment, sputum-smear nonconversion, and suburban living: The risk factors of multidrug-resistant tuberculosis among Malaysians.

    PubMed

    Mohd Shariff, Noorsuzana; Shah, Shamsul Azhar; Kamaludin, Fadzilah

    2016-03-01

    The number of multidrug-resistant tuberculosis patients is increasing each year in many countries all around the globe. Malaysia has no exception in facing this burdensome health problem. We aimed to investigate the factors that contribute to the occurrence of multidrug-resistant tuberculosis among Malaysian tuberculosis patients. An unmatched case-control study was conducted among tuberculosis patients who received antituberculosis treatments from April 2013 until April 2014. Cases are those diagnosed as pulmonary tuberculosis patients clinically, radiologically, and/or bacteriologically, and who were confirmed to be resistant to both isoniazid and rifampicin through drug-sensitivity testing. On the other hand, pulmonary tuberculosis patients who were sensitive to all first-line antituberculosis drugs and were treated during the same time period served as controls. A total of 150 tuberculosis patients were studied, of which the susceptible cases were 120. Factors found to be significantly associated with the occurrence of multidrug-resistant tuberculosis are being Indian or Chinese (odds ratio 3.17, 95% confidence interval 1.04-9.68; and odds ratio 6.23, 95% confidence interval 2.24-17.35, respectively), unmarried (odds ratio 2.58, 95% confidence interval 1.09-6.09), living in suburban areas (odds ratio 2.58, 95% confidence interval 1.08-6.19), are noncompliant (odds ratio 4.50, 95% confidence interval 1.71-11.82), were treated previously (odds ratio 8.91, 95% confidence interval 3.66-21.67), and showed positive sputum smears at the 2nd (odds ratio 7.00, 95% confidence interval 2.46-19.89) and 6th months of treatment (odds ratio 17.96, 95% confidence interval 3.51-91.99). Living in suburban areas, positive sputum smears in the 2nd month of treatment, and was treated previously are factors that independently contribute to the occurrence of multidrug-resistant tuberculosis. Those with positive smears in the second month of treatment, have a history of previous

  20. [Extrapulmonary tuberculosis].

    PubMed

    Ketata, W; Rekik, W K; Ayadi, H; Kammoun, S

    2015-01-01

    Each year, there are more than eight million new cases of tuberculosis and 1.3 million deaths. There is a renewed interest in extrapulmonary forms of tuberculosis as its relative frequency increases. Among extrapulmonary organs, pleura and lymph nodes are the most common. Their diagnosis is often difficult and is based on clinical, radiological, bacteriological and histological findings. Extrapulmonary lesions are paucibacillary and samplings, in most cases, difficult to obtain, so diagnosis is often simply presumptive. Nucleic acid amplification tests, which are fast and specific, have greatly facilitated the diagnosis of some forms of extrapulmonary tuberculosis. However, their sensitivity is poor and a negative test does not eliminate the diagnosis. Treatment is the same as for pulmonary forms, but its duration is nine to 12 months for central nervous system and for bone tuberculosis. Corticosteroids are indicated in meningeal and pericardial localizations. Complementary surgery is used for certain complicated forms. PMID:25131362

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

    PubMed Central

    Hunleth, Jean

    2013-01-01

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

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

    PubMed Central

    2015-01-01

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

  3. Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

    PubMed Central

    Adekambi, Toidi; Ibegbu, Chris C.; Cagle, Stephanie; Kalokhe, Ameeta S.; Wang, Yun F.; Hu, Yijuan; Day, Cheryl L.; Ray, Susan M.; Rengarajan, Jyothi

    2015-01-01

    BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4+ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection. METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4+ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment. RESULTS. Frequencies of Mtb-specific IFN-γ+CD4+ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38+IFN-γ+, HLA-DR+IFN-γ+, and Ki-67+IFN-γ+, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment. CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4+ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure. TRIAL REGISTRATION. Registration is not required for observational studies. FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center. PMID:25822019

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

    PubMed

    Field, Stephen K

    2015-07-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

    Takamatsu, I

    1999-11-01

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

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

    PubMed Central

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

    1997-01-01

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

  8. Risk Factors for Death during Pulmonary Tuberculosis Treatment in Korea: A Multicenter Retrospective Cohort Study

    PubMed Central

    2014-01-01

    The data regarding risk factors for death during tuberculosis (TB) treatment are inconsistent, and few studies examined this issue in Korea. The purpose of this study was to evaluate baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. A multicenter retrospective cohort study of 2,481 patients who received TB treatment at eight hospitals from January 2009 to December 2010 was performed. Successful treatment included cure (1,129, 45.5%) and treatment completion (1,204, 48.5%) in 2,333 patients (94.0%). Unsuccessful treatment included death (85, 3.4%) and treatment failure (63, 2.5%) occurred in 148 patients (6.0%). In multivariate analysis, male sex, anemia, dyspnea, chronic heart disease, malignancy, and intensive care unit (ICU) admission were significant risk factors for death during TB treatment. Therefore, male sex, anemia, dyspnea, chronic heart disease, malignancy, and ICU admission could be baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. Graphical Abstract PMID:25246740

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-07-01

    Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment. PMID:27108702

  12. High time to use rapid tests to detect multidrug resistance in sputum smear-negative tuberculosis in Belarus

    PubMed Central

    Kumar, A. M. V.; Skrahina, A.; Hurevich, H.; Astrauko, A.; de Colombani, P.; Tayler-Smith, K.; Dara, M.; Zachariah, R.

    2014-01-01

    Setting: Belarus (Eastern Europe) is facing an epidemic of multidrug-resistant tuberculosis (MDR-TB). In 2012, rapid molecular diagnostics were prioritised for sputum smear-positive pulmonary tuberculosis (PTB) patients to diagnose MDR-TB, while pulmonary sputum smear-negative pulmonary TB (SN-PTB) patients were investigated using conventional methods, often delaying the diagnosis of MDR-TB by 2–4 months. Objective: To determine the proportion of MDR-TB among SN-PTB patients registered in 2012 and associated clinical and demographic factors. Design: Retrospective cohort study using countrywide data from the national electronic TB register. Results: Of the 5377 TB cases registered, 2960 (55%) were SN-PTB. Of the latter, 1639 (55%) were culture-positive, of whom 768 (47%) had MDR-TB: 33% (363/1084) were new and 73% (405/555) previously treated patients. Previous history of treatment, age, region, urban residence, human immunodeficiency virus (HIV) status and being a pensioner were independently associated with MDR-TB. Conclusion: About half of culture-positive SN-PTB patients have MDR-TB and this rises to over 7/10 for retreatment cases. A national policy decision to extend rapid molecular diagnostics universally to all PTB patients, including SN-PTB, seems justified. Steps need to be taken to ensure implementation of this urgent priority, given the patient and public health implications of delayed diagnosis. PMID:26400703

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    1997-10-01

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

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

    PubMed Central

    2013-01-01

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

  16. [Smoking and tuberculosis].

    PubMed

    Underner, Michel; Perriot, Jean

    2012-12-01

    Smoking and tuberculosis represent two major world health issues particularly in developing countries. Tobacco smoke increases risk of Mycobaterium tuberculosis infection by several means: alteration of muco-ciliary clearance, reduced alveolar macrophage activity; immune-depression of pulmonary lymphocytes, reduction of cytotoxic activity of natural killer cells, alteration of the activity of the pulmonary dendritic cells. Both active and passive smoking increases the risk of latent tubercular infection and of pulmonary and extra-pulmonary tuberculosis. Active smoking increases the severity of pulmonary tuberculosis (gravity of radiological lesions). The diagnostic delay and recovery details are more important for smokers. Active smoking increases relapses of both pulmonary and extra-pulmonary tuberculosis after treatment with or without the Directly Observed Treatment Short course (DOTS) with poor observance of treatment. The mortality risk from tuberculosis is heightened among smokers. Smoking cessation represents an essential means of controlling tuberculosis epidemics in developing countries. PMID:22465718

  17. Implementation of Tuberculosis Intensive Case Finding, Isoniazid Preventive Therapy, and Infection Control ("Three I's") and HIV-Tuberculosis Service Integration in Lower Income Countries

    PubMed Central

    Charles, M. Katherine; Lindegren, Mary Lou; Wester, C. William; Blevins, Meridith; Sterling, Timothy R.; Dung, Nguyen Thi; Dusingize, Jean Claude; Avit-Edi, Divine; Durier, Nicolas; Castelnuovo, Barbara; Nakigozi, Gertrude; Cortes, Claudia P.; Ballif, Marie; Fenner, Lukas

    2016-01-01

    Setting World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control (“Three I’s”) for TB prevention and control among persons living with HIV. Objective To assess the implementation of the “Three I’s” of TB-control at HIV treatment sites in lower income countries. Design Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa. Results ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03). Conclusions Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status. PMID:27073928

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

    PubMed

    Li, Lan; Xi, Yuliang; Ren, Fu

    2016-03-01

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

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

    PubMed Central

    Li, Lan; Xi, Yuliang; Ren, Fu

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  1. A novel inhibitor of gyrase B is a potent drug candidate for treatment of tuberculosis and nontuberculosis mycobacterial infections.

    PubMed

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

    2015-03-01

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

  2. Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research

    PubMed Central

    Munro, Salla A; Lewin, Simon A; Smith, Helen J; Engel, Mark E; Fretheim, Atle; Volmink, Jimmy

    2007-01-01

    Background Tuberculosis (TB) is a major contributor to the global burden of disease and has received considerable attention in recent years, particularly in low- and middle-income countries where it is closely associated with HIV/AIDS. Poor adherence to treatment is common despite various interventions aimed at improving treatment completion. Lack of a comprehensive and holistic understanding of barriers to and facilitators of, treatment adherence is currently a major obstacle to finding effective solutions. The aim of this systematic review of qualitative studies was to understand the factors considered important by patients, caregivers and health care providers in contributing to TB medication adherence. Methods and Findings We searched 19 electronic databases (1966–February 2005) for qualitative studies on patients', caregivers', or health care providers' perceptions of adherence to preventive or curative TB treatment with the free text terms “Tuberculosis AND (adherence OR compliance OR concordance)”. We supplemented our search with citation searches and by consulting experts. For included studies, study quality was assessed using a predetermined checklist and data were extracted independently onto a standard form. We then followed Noblit and Hare's method of meta-ethnography to synthesize the findings, using both reciprocal translation and line-of-argument synthesis. We screened 7,814 citations and selected 44 articles that met the prespecified inclusion criteria. The synthesis offers an overview of qualitative evidence derived from these multiple international studies. We identified eight major themes across the studies: organisation of treatment and care; interpretations of illness and wellness; the financial burden of treatment; knowledge, attitudes, and beliefs about treatment; law and immigration; personal characteristics and adherence behaviour; side effects; and family, community, and household support. Our interpretation of the themes across all

  3. Epidemiology of drug-resistant tuberculosis among children and adolescents in South Africa, 2005–2010

    PubMed Central

    Moore, B. K.; Anyalechi, E.; van der Walt, M.; Smith, S.; Erasmus, L.; Lancaster, J.; Morris, S.; Ndjeka, N.; Ershova, J.; Ismail, N.; Burton, D.; Menzies, H.

    2016-01-01

    SUMMARY OBJECTIVE To describe the demographic and clinical characteristics of children and adolescents diagnosed with resistance to any anti-tuberculosis drug (drug-resistant tuberculosis; DR-TB) in South Africa. DESIGN We retrospectively reviewed medical records of all children (<13 years) and adolescents (13 to <18 years) with DR-TB at specialty hospitals in four South African provinces from 2005 to 2010. RESULTS During the review period, 774 children and adolescents (median age 11.3 years) were diagnosed with DR-TB at selected facilities. A high proportion of patients had a history of previous TB treatment (285/631; 45.2%), human immunodeficiency virus (HIV) infection (375/685; 54.7%), contact with a TB case (347/454; 76.4%), and smear-positive (443/729; 60.8%), cavitary (253/680, 38.7%) disease. Eighty-two per cent of patients with HIV infection received antiretroviral therapy. Of 626 patients diagnosed with multidrug-resistant TB (MDR-TB), 561 (89.6%) received a regimen consistent with national guidelines; the median length of treatment was 22 months (IQR 16–25). Among 400 patients with any DR-TB and a known outcome, 20.3% died during treatment. CONCLUSION Pediatric DR-TB in these provinces is characterized by complex clinical features at diagnosis, with one in five children dying during treatment. History of previous treatment and contact with a TB patient indicate opportunities for earlier diagnosis and treatment to improve outcomes. PMID:25946356

  4. Risk factors for unfavorable outcome of pulmonary tuberculosis in adults in Taipei, Taiwan.

    PubMed

    Yen, Yung-Feng; Yen, Muh-Yong; Shih, Hsiu-Chen; Deng, Chung-Yeh

    2012-05-01

    This study was undertaken to identify factors associated with unfavorable outcomes in patients with pulmonary tuberculosis (PTB) in Taipei, Taiwan in 2007-2008. Taiwanese adults with culture-positive PTB diagnosed in Taipei during the study period were included in this retrospective cohort study. Unfavorable outcomes were classified as treatment default, death, treatment failure, or transfer. Of 1616 eligible patients, 22.6% (365) had unfavorable outcomes, mainly death. After controlling for patient sociodemographic factors, clinical findings, and underlying disease, independent risk factors for unfavorable outcomes included advanced age, unemployment, end-stage renal disease requiring dialysis, malignancy, acid-fast bacilius smear-positivity, multidrug-resistant TB, and notification from ordinary ward or intensive care unit. In contrast, patients receiving directly observed treatment, and with a high school or higher education were significantly less likely to have unfavorable outcomes. This study advanced our understanding by revealing that a high school or higher education might lower the risk of an unfavorable outcome. Our results also confirmed the risk factors for unfavorable outcomes shown in previous research. Future TB control programmes in Taiwan should target particularly high-risk patients including those who had lower educational levels. PMID:22387265

  5. Benzothiazinethione is a potent preclinical candidate for the treatment of drug-resistant tuberculosis

    PubMed Central

    Gao, Chao; Peng, Cuiting; Shi, Yaojie; You, Xinyu; Ran, Kai; Xiong, Lu; Ye, Ting-hong; Zhang, Lidan; Wang, Ningyu; Zhu, Yongxia; Liu, Kun; Zuo, Weiqiong; Yu, Luoting; Wei, Yuquan

    2016-01-01

    New chemotherapeutic compounds are needed to combat multidrug-resistant Mycobacterium tuberculosis (Mtb), which remains a serious public-health challenge. Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1 enzyme) has been characterized as an attractive therapeutic target to address this urgent demand. Herein, we have identified a new class of DprE1 inhibitors benzothiazinethiones as antitubercular agents. Benzothiazinethione analogue SKLB-TB1001 exhibited excellent activity against Mtb in the Microplate Alamar blue assay and intracellular model, meanwhile SKLB-TB1001 was also highly potent against multi-drug resistant extensively and drug resistant clinical isolates. Importantly, no antagonism interaction was found with any two-drug combinations tested in the present study and the combination of SKLB-TB1001 with rifampicin (RMP) was proved to be synergistic. Furthermore, benzothiazinethione showed superb in vivo antitubercular efficacy in an acute Mtb infection mouse model, significantly better than that of BTZ043. These data combined with the bioavailability and safety profiles of benzothiazinethione indicates SKLB-TB1001 is a promising preclinical candidate for the treatment of drug-resistant tuberculosis. PMID:27405961

  6. Successful Treatment in a Child with Anaplastic Large Cell Lymphoma and Coexistence of Pulmonary Tuberculosis

    PubMed Central

    Baka, Margarita; Pourtsidis, Apostolos; Tsolia, Maria; Bouhoutsou, Despina; Varvoutsi, Maria; Strantzia, Katerina; Kosmidis, Helen

    2013-01-01

    A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL), whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR) in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months), pyrazinamide (the first 2 months), and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time. PMID:23841007

  7. Successful treatment in a child with anaplastic large cell lymphoma and coexistence of pulmonary tuberculosis.

    PubMed

    Baka, Margarita; Doganis, Dimitrios; Pourtsidis, Apostolos; Tsolia, Maria; Bouhoutsou, Despina; Varvoutsi, Maria; Strantzia, Katerina; Kosmidis, Helen

    2013-01-01

    A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL), whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR) in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months), pyrazinamide (the first 2 months), and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time. PMID:23841007

  8. Tissue Penetration of a Novel Spectinamide Antibiotic for the Treatment of Tuberculosis.

    PubMed

    Madhura, Dora Babu; Trivedi, Ashit; Liu, Jiuyu; Boyd, Vincent A; Jeffries, Cynthia; Loveless, Vivian; Lee, Richard E; Meibohm, Bernd

    2016-05-01

    The in vivo biodistribution and pharmacokinetics of 1329, a novel spectinamide antibiotic with anti-tubercular activity, were studied during intravenous administration of an tritium-labeled compound for nine consecutive, 12-hourly doses to rats. Serial blood samples were collected after the first and the eighth dose, and major organs and tissues were collected 1 h after the ninth dose. Urinary and fecal excretion was monitored throughout the dosing period. Radioactivity in the collected samples was assessed by scintillation counting. During the course of treatment, 86.6% of the administered radioactivity was recovered in urine, feces, organs, and muscle tissue. Urinary excretion was the major route of elimination, with 70% of radioactivity recovered from urine and 12.6% from feces. The time profiles of radioactivity in serum after the first and the eighth dose were identical for the first 2 h post-dose, with similar Cmax (3.39 vs. 3.55 mCi/L) and AUC0-τ (5.08 vs. 5.17 mCi • h/L), indicating no substantial accumulation of 1329 during multiple dosing. Radioactivity in major target organs for pulmonary tuberculosis infection, the lungs and spleen, was 2.79- and 3.06-fold higher than in the blood. Similarly, the intracellular uptake of 1329 into macrophages was sixfold higher than for streptomycin. Overall, these observations suggest biodistribution properties favorable for targeting pulmonary tuberculosis infections. PMID:26984832

  9. Costs associated with tuberculosis diagnosis and treatment in Yemen for patients and public health services.

    PubMed

    Othman, G Q; Ibrahim, M I M; Raja'a, Y A

    2012-04-01

    This study determined the costs associated with tuberculosis (TB) diagnosis and treatment for the public health services and patients in Sana'a, Yemen. Data were collected prospectively from 320 pulmonary and extrapulmonary TB patients (160 each) who were followed until completion of treatment. Direct medical and nonmedical costs and indirect costs were calculated. The proportionate cost to the patients for pulmonary TB and extrapulmonary TB was 76.1% arid 89.4% respectively of the total for treatment. The mean cost to patients for pulmonary and extrapulmonary TB treatment was US$ 108.4 and US$ 328.0 respectively. The mean cost per patient to the health services for pulmonary and extrapulmonary TB treatment was US$ 34.0 and US$ 38.8 respectively. For pulmonary and extrapulmonary TB, drug treatment represented 59.3% and 77.9% respectively of the total cost to the health services. The greatest proportionate cost to patients for pulmonary TB treatment was time away from work (67.5% of the total cost), and for extrapulmonary TB was laboratory and X-ray costs (55.5%) followed by transportation (28.6%). PMID:22768704

  10. Within patient microevolution of Mycobacterium tuberculosis correlates with heterogeneous responses to treatment.

    PubMed

    Liu, Qingyun; Via, Laura E; Luo, Tao; Liang, Lili; Liu, Xin; Wu, Sufang; Shen, Qingyu; Wei, Wang; Ruan, Xianglin; Yuan, Xing; Zhang, Guolong; Barry, Clifton E; Gao, Qian

    2015-01-01

    Genetic heterogeneity of Mycobacterium tuberculosis (MTB) within a patient has caused great concern as it might complicate antibiotic treatment and cause treatment failure. But the extent of genetic heterogeneity has not been described in detail nor has its association with heterogeneous treatment response. During treatment of a subject with MDR-TB, serial computed tomography (CT) scans showed this subject had six anatomically discrete lesions and they responded to treatment with disparate kinetics, suggesting heterogeneous MTB population may exist. To investigate this heterogeneity, we applied deep whole genome sequencing of serial sputum isolates and discovered that the MTB population within this patient contained three dominant sub-clones differing by 10 ~ 14 single nucleotide polymorphisms (SNPs). Differential mutation patterns in known resistance alleles indicated these sub-clones had different drug-resistance patterns, which may explain the heterogeneous treatment responses between lesions. Our results showed clear evidence of branched microevolution of MTB in vivo, which led to a diverse bacterial community. These findings indicated that complex sub-populations of MTB might coexist within patient and contribute to lesions' disparate responses to antibiotic treatment. PMID:26620446

  11. [The prevention of neurotoxic reactions during the treatment of pulmonary tuberculosis in middle-aged and elderly patients].

    PubMed

    Markova, E F

    1990-10-01

    To prevent and control neurotoxic reactions in the treatment of pulmonary tuberculosis in elderly and old patients the author used dipromonium (derivative of pangamic acid). Use of this agent at the beginning of the treatment course reduced the incidence of side-effects of neurotoxic character. In case of development of reactions of the central and peripheral nervous system dipromonium treatment resulted in their weakening or liquidation. PMID:2080583

  12. [Possibilities of intravenous use of helium-neon laser in the treatment of experimental tuberculosis of animals].

    PubMed

    Topol'nitskiĭ, V G; Maliev, B M; Gracheva, M P; Kruglova, E G

    1992-01-01

    The study presents experimental finding of 40 mongrel dogs whose intravascular blood was irradiated with laser as a supplement to the multimodality treatment of respiratory tuberculosis. Earlier disappearance of intoxication symptoms and reduced terms of destruction cavity decrease and closure, as roentgenologically evidenced, was achieved. The influence of this treatment on certain lipid peroxidation parameters, hemocoagulation, immunity status and bacteriostatic blood activity were found. There were no side effects during treatment. PMID:1409508

  13. Perceptions of tuberculosis and treatment seeking behaviour in Ilala and Kinondoni Municipalities in Tanzania.

    PubMed

    Kilale, A M; Mushi, A K; Lema, L A; Kunda, J; Makasi, C E; Mwaseba, D; Range, N S; Mfinanga, G S

    2008-04-01

    This study was carried out in Ilala and Kinondoni Municipalities in Tanzania to explore the perceptions of Tuberculosis (TB), and treatment seeking behaviour, among patients attending healthcare facilities. The study was conducted in four randomly selected health facilities providing directly observed treatment (DOT). Exit interviews were administered to 69 randomly selected TB patients. The mean age of the respondents was 33.2 years (range = 11-72 years). Forty-six (66.7%) of the patients had primary school education. Fifty-nine (84.1%) patients had good knowledge on the transmission of TB. Majority (75%) of the respondents were of the opinion that the incidence of TB was on the increase and this was mainly associated with HIV/AIDS epidemic. All respondents knew that TB was a curable disease if one complies with the treatment. Sixty-four (60%) respondents had good knowledge on the correct duration of tuberculosis treatment. The median duration before seeking treatment from a health facility was 1.5 months. The majority of the patients 47 (68%) visited public health facilities for treatment as their first action. Overall, 83.8% (57/68) respondents said females comply better with treatment than male patients. The majority of the respondents lived within a walking distance to a healthcare facility. Only 18.8% (13/69) had to spend an average of US$ 0.2-0.3 as travel costs to the healthcare facility. Most of the respondents (57.8%) said they were well attended by service providers. Half (21/42) and 59.3% (16/27) of the males and females, respectively, mentioned good patient-service provider relationship as an important reason for satisfaction of the service (chi2 = 0.57, df = 1, P > 0.005). Twenty-nine (42%) of respondents were of the opinion that female TB patients conformed better to treatment than males and a similar number thought that both of them equally conformed to treatment. Findings from this study indicate that a large population in urban settings are aware

  14. Outcomes and follow-up of patients treated for multidrug-resistant tuberculosis in Orel, Russia, 2002–2005

    PubMed Central

    Cavanaugh, J. S.; Kazennyy, B. Y.; Nguyen, M. L.; Kiryanova, E. V.; Vitek, E.; Khorosheva, T. M.; Nemtsova, E.; Cegielski, J. P.

    2015-01-01

    SUMMARY SETTING Multidrug-resistant tuberculosis (MDR-TB) treatment facility, Orel Oblast, Russian Federation. OBJECTIVES To determine factors associated with poor outcome and to document status of patients after recording of TB outcomes. DESIGN Retrospective review of prospective single cohort. RESULTS Among 192 patients, factors significantly associated with poor outcome in multivariate analysis include three or more treatment interruptions during the intensive phase of therapy and alcohol or drug addiction (adjusted OR [aOR] 2.1, 95%CI 1.0–4.3 and aOR 1.9, 95%CI 1.0–3.7). Previous treatment was associated with poor outcome, but only among smear-positive patients (aOR 3.1, 95%CI 1.3–7.3). Ten patients (5%) developed extensively drug-resistant TB (XDR-TB) during treatment; of 115 patients with at least 6 months of follow-up data after outcomes were recorded, 13 (11%) developed XDR-TB. CONCLUSION Interventions focused on supporting patient adherence during the intensive phase of treatment; the management of drug and alcohol addiction should be developed and studied. A substantial proportion of patients developed XDR-TB during and after treatment. Longer term follow-up data of patients treated for MDR-TB are needed to better inform programmatic policy. PMID:22691694

  15. Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.

    PubMed

    Nahid, Payam; Dorman, Susan E; Alipanah, Narges; Barry, Pennan M; Brozek, Jan L; Cattamanchi, Adithya; Chaisson, Lelia H; Chaisson, Richard E; Daley, Charles L; Grzemska, Malgosia; Higashi, Julie M; Ho, Christine S; Hopewell, Philip C; Keshavjee, Salmaan A; Lienhardt, Christian; Menzies, Richard; Merrifield, Cynthia; Narita, Masahiro; O'Brien, Rick; Peloquin, Charles A; Raftery, Ann; Saukkonen, Jussi; Schaaf, H Simon; Sotgiu, Giovanni; Starke, Jeffrey R; Migliori, Giovanni Battista; Vernon, Andrew

    2016-10-01

    The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the

  16. Is nonstructural bone graft useful in surgical treatment of lumbar spinal tuberculosis?

    PubMed Central

    Liu, Jia-Ming; Chen, Xuan-Yin; Zhou, Yang; Long, Xin-Hua; Chen, Wen-Zhao; Liu, Zhi-Li; Huang, Shan-Hu; Yao, Hao-Qun

    2016-01-01

    Abstract Surgical intervention is an important option for treating spinal tuberculosis. Previous studies have reported different surgical procedures and bone grafts for it. To our knowledge, few studies demonstrated the clinical results of using nonstructural autogenous bone graft in surgical treatment of spinal tuberculosis. The purpose of this study is to compare the clinical outcomes of surgical management lumbar spinal tuberculosis by one-stage posterior debridement with nonstructural autogenous bone grafting and instrumentation versus anterior debridement, strut bone grafting combined with posterior instrumentation. A total of 58 consecutive patients who underwent surgical treatment due to lumbar spinal tuberculosis from January 2011 to December 2013 were included. A total of 22 patients underwent one-stage posterior debridement, nonstructural autogenous bone grafting, and instrumentation (group A), and 36 patients received anterior debridement, strut bone grafting combined with posterior instrumentation (group B). The operative duration, total blood loss, perioperative transfusion, length of hospital stay, hospitalization cost, and complications were recorded. The bony fusion of the graft was assessed by computed tomography scans. American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate the neurological function of patients in the 2 groups. All the patients were followed up, with a mean follow-up duration of 21.6 ± 5.7 months in group A and 22.3 ± 6.2 months in group B (P = 0.47). The average operative duration was 257.5 ± 91.1 minutes in group A and 335.7 ± 91.0 minutes in group B (P = 0.002). The mean total blood loss was 769.6 ± 150.9 mL in group A and 1048.6 ± 556.9 mL in group B (P = 0.007). Also, significant differences were found between the 2 groups in perioperative transfusion volumes, length of hospital stay, and hospitalization cost (P < 0.05), which were less in group A

  17. Time to unsuccessful tuberculosis treatment outcome, Cambodia, China, and Viet Nam

    PubMed Central

    Sokun, C.; Wei, C.; Lauritsen, J. M.; Rieder, H. L.

    2012-01-01

    Objective: To determine the frequency and characteristics of patients with unsuccessful tuberculosis (TB) treatment. Methods: Random selection of TB case registers among all treatment units in Cambodia, two provinces in China, and Viet Nam. The data of two calendar years were analyzed to assess unsuccessful outcomes and their time of occurrence. Results: Among the 33 309 TB patients, treatment was unsuccessful in respectively 10.1%, 3.0% and 9.1% of patients in Cambodia, China and Viet Nam. The risk of death was highest in Cambodia, higher among males than females, increased with age, and was more common among retreatment cases than new cases, and among patients with a high than a low sputum smear microscopy grade. Half of all deaths occurred in the first 2 months in Cambodia and within 11 weeks in China and Viet Nam. Median time to default was 3 months in Cambodia and Viet Nam, and about 2 months in China. Conclusions: Treatment was highly successful in the three study countries, with a low proportion of death and default. As the majority of defaulting occurs at the beginning of treatment, all countries should critically review their current policy of treatment support in this period. PMID:26392939

  18. Viewpoint: adapting to new international tuberculosis treatment standards with medication monitors and DOT given selectively.

    PubMed

    Moulding, Thomas S

    2007-11-01

    New international standards no longer require directly observed therapy for all tuberculosis (TB) patients, but state that practitioners must be capable of assessing adherence and addressing poor adherence. Mass-produced electronic medication monitors, which record removal of medication from a container, could help overcome the problem of assessing treatment adherence accurately even in poor countries. Both health facilities and community workers could dispense drugs for self-administered treatment in medication monitors and retrieve the adherence record with inexpensive built-in displays. These devices could keep the adherence record from the beginning of therapy for managing patients who move. Pharmacists using medication monitors could provide surveillance of self-administered treatment prescribed by private physicians with less adherent patients referred to the health departments. Less adherent patients could be managed with focused counselling, directly observed therapy when necessary, and extensions in treatment duration. Removal of the directly observed therapy burden would encourage patients to seek free high-quality supervised pubic care and help expand effective TB treatment services. If resources saved by giving less directly observed therapy were focused on poorly adherent patients, medication monitor-based programmes could create less acquired drug resistance than overwhelmed treatment programmes that attempt but fail to give uninterrupted directly observed therapy to all patients. PMID:17949402

  19. Incidence, Clinical Features and Impact on Anti-Tuberculosis Treatment of Anti-Tuberculosis Drug Induced Liver Injury (ATLI) in China

    PubMed Central

    Shang, Penghui; Xia, Yinyin; Liu, Feiying; Wang, Xiaomeng; Yuan, Yanli; Hu, Daiyu; Tu, Dehua; Chen, Yixin; Deng, Peiyuan; Cheng, Shiming; Zhou, Lin; Ma, Yu; Zhu, Lizhen; Gao, Weiwei; Wang, Hongyuan; Chen, Dafang; Yang, Li; He, Pingping; Wu, Shanshan; Tang, Shaowen; Lv, Xiaozhen; Shu, Zheng; Zhang, Yuan; Yang, Zhirong; Chen, Yan; Li, Na; Sun, Feng; Li, Xiaoting; He, Yingjian; Garner, Paul; Zhan, Siyan

    2011-01-01

    Background Anti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China. Methodology/Principal Findings In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%–3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69–15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI,1.23–3.60) risk of prolonged intensive treatment phase. Conclusions/Significance ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the

  20. Barriers and enablers in the management of tuberculosis treatment in Addis Ababa, Ethiopia: a qualitative study

    PubMed Central

    Sagbakken, Mette; Frich, Jan C; Bjune, Gunnar

    2008-01-01

    Background Non-adherence to tuberculosis (TB) treatment is an important barrier for TB control programs because incomplete treatment may result in prolonged infectiousness, drug resistance, relapse, and death. The aim of the present study is to explore enablers and barriers in the management of TB treatment during the first five months of treatment in Addis Ababa, Ethiopia. Methods Qualitative study which included 50 in-depth interviews and two focus groups with TB patients, their relatives and health personnel. Results We found that loss of employment or the possibility to work led to a chain of interrelated barriers for most TB patients. Daily treatment was time-consuming and physically demanding, and rigid routines at health clinics reinforced many of the emerging problems. Patients with limited access to financial or practical help from relatives or friends experienced that the total costs of attending treatment exceeded their available resources. This was a barrier to adherence already during early stages of treatment. A large group of patients still managed to continue treatment, mainly because relatives or community members provided food, encouragement and sometimes money for transport. Lack of income over time, combined with daily accumulating costs and other struggles, made patients vulnerable to interruption during later stages of treatment. Patients who were poor due to illness or slow progression, and who did not manage to restore their health and social status, were particularly vulnerable to non-adherence. Such patients lost access to essential financial and practical support over time, often because relatives and friends were financially and socially exhausted by supporting them. Conclusion Patients' ability to manage TB treatment is a product of dynamic processes, in which social and economic costs and other burdens change and interplay over time. Interventions to facilitate adherence to TB treatment needs to address both time-specific and local

  1. Tuberculosis treatment and risk of stavudine substitution in first line antiretroviral therapy

    PubMed Central

    Westreich, Daniel J.; Sanne, Ian; Maskew, Mhairi; Malope-Kgokong, Babatyi; Conradie, Francesca; Majuba, Pappie; Funk, Michele Jonsson; Kaufman, Jay S.; Van Rie, Annelies; MacPhail, Patrick

    2009-01-01

    Background Treatment for tuberculosis (TB) is common among individuals receiving stavudine-containing highly active antiretroviral therapy (HAART), but the effect of TB treatment on stavudine toxicity has received little attention. We estimated the effect of TB treatment on risk of stavudine substitution among individuals receiving first-line HAART. Methods We evaluated a cohort of 7,066 patients who initiated HAART between April 2004 and March 2007 in Johannesburg, South Africa. Three exposure categories were considered: ongoing TB treatment at HAART initiation; concurrent initiation of TB treatment and HAART; incident TB treatment after HAART initiation. The outcome was single-drug stavudine substitution. Adjusted hazard ratios (aHRs) were estimated using marginal structural models to control for confounding, loss to follow-up, and competing risks. Results Individuals with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dose. For ongoing TB treatment, aHR was 3.18 (95% confidence interval [CI] 1.82-5.56) in the first two months of HAART, 2.51 (95% CI 1.77-3.54) in months 3-6, and 1.19 (95% CI 0.94-1.52) thereafter. For concurrent TB treatment, aHR was 6.60 (95% CI 3.03-14.37) in the first two months,1.88 (95% CI 0.87-4.09) in months 3-6, and 1.07 (95% CI 0.65-1.76) thereafter. There was no effect of incident TB on stavudine substitution risk. Conclusions Risk of stavudine substitution was increased among patients receiving TB treatment, especially soon after HAART initiation. In settings where alternative antiretroviral drugs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered. PMID:19385733

  2. Associations between national tuberculosis program budgets and tuberculosis outcomes: an ecological study

    PubMed Central

    Chapple, Will; Katz, Alan Roy; Li, Dongmei

    2012-01-01

    Introduction The objective of this study is to explore the associations between national tuberculosis program (NTP) budget allocation and tuberculosis related outcomes in the World Health Organization's 22 high burden countries from 2007–2009. Methods This ecological study used mixed effects and generalized estimating equation models to identify independent associations between NTP budget allocations and various tuberculosis related outcomes. Models were adjusted for a number of independent variables previously noted to be associated with tuberculosis incidence. Results Increasing the percent of the NTP budget for advocacy, communication and social mobilization was associated with an increase in the case detection rate. Increasing TB-HIV funding was associated with an increase in HIV testing among TB patients. Increasing the percent of the population covered by the Directly Observed Therapy (DOT) program was associated with an increase in drug susceptibility testing. Laboratory funding was positively associated with tuberculosis notification. Increasing the budgets for first line drugs, management and multi-drug resistant tuberculosis (MDR-TB) was associated with a decrease in smear positive deaths. Conclusion Effective TB control is a complex and multifaceted challenge. This study revealed a number of budget allocation related factors associated with improved TB outcome parameters. If confirmed with future longitudinal studies, these findings could help guide NTP managers with allocation decisions. PMID:23024825

  3. Risk factors for nosocomial tuberculosis transmission among health care workers.

    PubMed

    Ito, Yutaka; Nagao, Miki; Iinuma, Yoshitsugu; Matsumura, Yasufumi; Yamamoto, Masaki; Takakura, Shunji; Igawa, Junko; Yamanaka, Hiroe; Hashimoto, Akiko; Hirai, Toyohiro; Niimi, Akio; Ichiyama, Satoshi; Mishima, Michiaki

    2016-05-01

    We conducted hospital-based contact investigations of 55 serial sputum smear-positive tuberculosis (TB) patients and 771 health care workers (HCWs) from 2006-2013. HCWs who made contact with TB patients in the absence of appropriate airborne precautions were evaluated using interferon gamma release assays to identify TB infection. Twenty-nine HCWs (3.8%) were newly diagnosed with TB infection. The 10 TB patients responsible for transmission had a duration of contact of >7 days by multivariate analysis. PMID:26777287

  4. The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis

    PubMed Central

    Chung, Wou Young; Yoon, Dukyong; Lee, Keu Sung; Jung, Yun Jung; Kim, Young Sun; Sheen, Seung Soo; Park, Kwang Joo

    2016-01-01

    Abstract Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB. We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into “fast” and “slow” based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as “significant.” In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-γ levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%–93%), while specificity (92%–96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P

  5. Psychological distress and its effect on tuberculosis treatment outcomes in Ethiopia

    PubMed Central

    Tola, Habteyes Hailu; Shojaeizadeh, Davoud; Garmaroudi, Gholamreza; Tol, Azar; Yekaninejad, Mir Saeed; Ejeta, Luche Tadesse; Kebede, Abebaw; Karimi, Mehrdad; Kassa, Desta

    2015-01-01

    Background Psychological distress is the major comorbidity among tuberculosis (TB) patients. However, its magnitude, associated factors, and effect on treatment outcome have not been adequately studied in low-income countries. Objective This study aimed to determine the magnitude of psychological distress and its effect on treatment outcome among TB patients on treatment. Design A follow-up study was conducted in Addis Ababa, Ethiopia, from May to December 2014. Patients (N=330) diagnosed with all types of TB who had been on treatment for 1–2 months were enrolled consecutively from 15 randomly selected health centers and one TB specialized hospital. Data on sociodemographic variables and economic status were collected using a structured questionnaire. The presence of psychological distress was assessed at baseline (within 1–2 months after treatment initiation) and end point (6 months after treatment initiation) using the 10-item Kessler (K-10) scale. Alcohol use and tobacco smoking history were assessed using WHO Alcohol Use Disorder Identification Test and Australian Smoking Assessment Checklist, respectively. The current WHO TB treatment outcome definition was used to differentiate the end result of each patient at completion of the treatment. Results The overall psychological distress was 67.6% at 1–2 months and 48.5% at 6 months after treatment initiation. Multiple logistic regression analysis revealed that past TB treatment history [adjusted odds ratio (AOR): 3.76; 95% confidence interval (CI): 1.67–8.45], being on anti-TB and anti-HIV treatments (AOR: 5.35; 95% CI: 1.83–15.65), being unmarried (AOR: 4.29; 95% CI: 2.45–7.53), having alcohol use disorder (AOR: 2.95; 95% CI: 1.25–6.99), and having low economic status (AOR: 4.41; 95% CI: 2.44–7.97) were significantly associated with psychological distress at baseline. However, at 6 months after treatment initiation, only being a multidrug-resistant tuberculosis (MDR-TB) patient (AOR: 3.02; 95% CI

  6. The effectiveness of sputum pH analysis in the prediction of response to therapy in patients with pulmonary tuberculosis.

    PubMed

    Masuda, Makoto; Sato, Takashi; Sakamaki, Kentaro; Kudo, Makoto; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2015-01-01

    Purpose. The predictive factor of response to antituberculous therapy has not been fully elucidated. Airway acidity has been thought to be a potential indicator of the bactericidal activity. Therefore, we hypothesized that monitoring airway acidity by measuring sputum pH could predict response to therapy. Methods. A total of 47 patients having newly diagnosed, smear-positive, active pulmonary tuberculosis were enrolled between October 2011 and March 2014. Sputum samples were serially analyzed before and after treatment. Eligible patients who initiated a standard 6-month treatment were monitored for the length of time to sputum smear and culture conversion. Results. There were 39 patients who completed a 2-month intensive phase of isoniazid, rifampicin, pyrazinamide, and ethambutol therapy followed by a 4-month continuation phase of isoniazid and rifampicin. Although factors including age, cavitation, sputum grade, and use of an acid-suppressant were associated with initial low sputum pH in univariate analysis, multivariate analysis revealed that only age ≥61 years was a statistically important factor predicting low pH value (p = 0.005). Further outcome analysis showed that initial low sputum pH before treatment was the only factor significantly associated with shorter length of time to both sputum smear and culture conversion (p = 0.034 and 0.019, respectively) independent of the effects of age, sputum bacterial load, extent of lung lesion, and cavitation. Thus, initial low sputum pH indicated favorable response to anti-tuberculosis therapy. Conclusions. Measuring sputum pH is an easy and inexpensive way of predicting response to standard combination therapy in patients with pulmonary tuberculosis. PMID:26644982

  7. The effectiveness of sputum pH analysis in the prediction of response to therapy in patients with pulmonary tuberculosis

    PubMed Central

    Masuda, Makoto; Sakamaki, Kentaro; Kudo, Makoto; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2015-01-01

    Purpose. The predictive factor of response to antituberculous therapy has not been fully elucidated. Airway acidity has been thought to be a potential indicator of the bactericidal activity. Therefore, we hypothesized that monitoring airway acidity by measuring sputum pH could predict response to therapy. Methods. A total of 47 patients having newly diagnosed, smear-positive, active pulmonary tuberculosis were enrolled between October 2011 and March 2014. Sputum samples were serially analyzed before and after treatment. Eligible patients who initiated a standard 6-month treatment were monitored for the length of time to sputum smear and culture conversion. Results. There were 39 patients who completed a 2-month intensive phase of isoniazid, rifampicin, pyrazinamide, and ethambutol therapy followed by a 4-month continuation phase of isoniazid and rifampicin. Although factors including age, cavitation, sputum grade, and use of an acid-suppressant were associated with initial low sputum pH in univariate analysis, multivariate analysis revealed that only age ≥61 years was a statistically important factor predicting low pH value (p = 0.005). Further outcome analysis showed that initial low sputum pH before treatment was the only factor significantly associated with shorter length of time to both sputum smear and culture conversion (p = 0.034 and 0.019, respectively) independent of the effects of age, sputum bacterial load, extent of lung lesion, and cavitation. Thus, initial low sputum pH indicated favorable response to anti-tuberculosis therapy. Conclusions. Measuring sputum pH is an easy and inexpensive way of predicting response to standard combination therapy in patients with pulmonary tuberculosis. PMID:26644982

  8. Exploring tuberculosis patients' adherence to treatment regimens and prevention programs at a public health site.

    PubMed

    Naidoo, Pamela; Dick, Judy; Cooper, Diane

    2009-01-01

    Our aim with this study was to explore the factors that contribute to tuberculosis patients' adherence and nonadherence to the Directly Observed Treatment Short Course strategy. A qualitative, phenomenological research design was used. Fifteen male and female participants between the ages of 18 and 57 years were recruited through purposive sampling at a primary care clinic located in a disadvantaged area, and in-depth interviews were conducted. The data analysis indicated that the factors found to influence adherence were social and economic resources; causal attributions assigned to TB; the social, cultural, economic, disease-related, and psychological challenges faced as a consequence of having TB; quality of health care received; use of the traditional healing system; and the participants' HIV status. Factors found to be associated with nonadherence included poverty, HIV co-infection, stigma, unsupportive social and work environments, and a high prevalence of helplessness and hopelessness. PMID:18997153

  9. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment

    PubMed Central

    Pienaar, Elsje; Cilfone, Nicholas A.; Lin, Philana Ling; Dartois, Véronique; Mattila, Joshua T.; Butler, Russ; Flynn, JoAnne L.; Kirschner, Denise E.; Linderman, Jennifer J.

    2014-01-01

    While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials. The site of infection in TB is the granuloma, a collection of immune cells and bacteria that form in the lung, and new data suggest that penetration of drugs throughout granulomas is problematic. Here we integrate our computational model of granuloma formation and function with models for plasma pharmacokinetics, lung tissue pharmacokinetics and pharmacodynamics for two first line anti-TB antibiotics. The integrated model is calibrated to animal data. We make four predictions. First, antibiotics are frequently below effective concentrations inside granulomas, leading to bacterial growth between doses and contributing to the long treatment periods required for TB. Second, antibiotic concentration gradients form within granulomas, with lower concentrations toward their centers. Third, during antibiotic treatment, bacterial subpopulations are similar for INH and RIF treatment: mostly intracellular with extracellular bacteria located in areas non-permissive for replication (hypoxic areas), presenting a slowly increasing target population over time. Finally, we find that on an individual granuloma basis, pre-treatment infection severity (including bacterial burden, host cell activation and host cell death) is predictive of treatment outcome. PMID:25497475

  10. Food incentives improve adherence to tuberculosis drug treatment among homeless patients in Russia.

    PubMed

    Gärden, Bodil; Samarina, Arina; Stavchanskaya, Irina; Alsterlund, Rolf; Övregaard, Amanda; Taganova, Olga; Shpakovskaya, Ludmilla; Zjemkov, Vladimir; Ridell, Malin; Larsson, Lars-Olof

    2013-03-01

    The aim of the study was to evaluate the impact of food incentives on adherence to tuberculosis (TB) drug treatment among homeless patients with TB. Food packages were thus given as a part of directly observed therapy to 142 homeless patients with TB at a dispensary in Saint Petersburg, Russian Federation. In addition, a social worker provided the patients with information and legal assistance, for example help with internal passports. Among the 142 patients, 66 were included in the study at the dispensary during their entire treatment period, while 76 patients were included in the study during shorter periods mainly because of transfer to inpatient care. In the first group, 59% of the patients continued the TB drug treatment without interruption in contrast to 31% in a control group. In the second group, that is those studied during shorter periods, 95% continued the TB drug treatment without interruption while attached to the dispensary. Food was introduced in the TB programme of the City of St. Petersburg as a consequence of this study. In conclusion, it can be stated that the food incentive had a strong positive impact on the adherence to TB drug treatment among these socially marginalized patients. The social support contributed in all probability also to the positive results. PMID:22671304

  11. Identification of multidrug resistance in previously treated tuberculosis patients: a mixed methods study in Cambodia

    PubMed Central

    Royce, S; Khann, S; Yadav, RP; Mao, ET; Cattamanchi, A; Sam, S; Handley, MA

    2014-01-01

    SUMMARY Setting Previously treated tuberculosis (TB) patients are a priority for drug susceptibility testing (DST) to identify cases with multidrug resistance (MDR). In Cambodia, a recent study found that only one-third of smear-positive previously treated patients had DST results. Objective To quantify the gaps in detecting MDR in previously treated TB patients in Cambodia, and describe health workers’ perspectives on barriers, facilitators and potential interventions. Design We analyzed case notifications in Cambodia (2004–2012) and conducted semi-structured interviews with key stakeholders Results The proportion of previously treated notifications varied significantly across provinces 2010–12, in the context of longer term trends of decreasing relapse and increasing “other” retreatment notifications. Correct classification of patients’ TB treatment history and ensuring specimens from previously-treated patients are collected and reach the laboratory could nearly double the number of detected MDR-TB cases. Identified barriers include patients’ reluctance to disclose and staff difficulty eliciting treatment history, partly due to availability of streptomycin only in hospitals. Facilitators include trained health workers, collection of sputum for DST even if previously treated patients are not taking streptomycin, streamlining sputum transportation and promptly reporting results. Conclusion Improved monitoring, supportive supervision, and correctly classifying previously treated patients are essential for improving detection of MDR-TB. PMID:25299861

  12. The prevention and treatment of isoniazid toxicity in the therapy of pulmonary tuberculosis

    PubMed Central

    1963-01-01

    A recent report from the Tuberculosis Chemotherapy Centre, Madras, showed that a vitamin-B-complex preparation containing a small amount of pyridoxine (as well as aneurine hydrochloride, riboflavine, nicotinamide, panthenol and cyanocobalamin) was effective in the treatment of peripheral neuropathy caused by daily high-dosage (12.5-15.2 mg/kg body-weight) isoniazid therapy of pulmonary tuberculosis. The present report gives results which show that the B-complex preparation is fully effective in preventing peripheral neuropathy in patients receiving the same high dosage of isoniazid, and that this is due to the small pyridoxine content of only 6 mg daily, and not to any of its other constituents. The low cost of this small dose of pyridoxine makes high-dosage isoniazid therapy, given in combination with other drugs or alone, a possible proposition in developing countries. Studies in the Centre have produced clear evidence that there is an increase in the frequency of peripheral neuropathy when the dosage of isoniazid is increased from 7.8-9.6 mg/kg body-weight to 12.5-15.6 mg/kg daily, and that its incidence is higher among slow than among rapid inactivators of isoniazid. The studies also show that increasing the dosage of isoniazid when given alone from a moderate daily dosage of 7.8-9.6 mg/kg to the high daily dosage of 12.5-15.6 mg/kg has not materially altered the radiographic or the bacteriological response to treatment. PMID:14099673

  13. Patients Are Paying Too Much for Tuberculosis: A Direct Cost-Burden Evaluation in Burkina Faso

    PubMed Central

    Laokri, Samia; Drabo, Maxime Koiné; Weil, Olivier; Kafando, Benoît; Dembélé, Sary Mathurin; Dujardin, Bruno

    2013-01-01

    Background Paying for health care may exclude poor people. Burkina Faso adopted the DOTS strategy implementing “free care” for Tuberculosis (TB) diagnosis and treatment. This should increase universal health coverage and help to overcome social and economic barriers to health access. Methods Straddling 2007 and 2008, in-depth interviews were conducted over a year among smear-positive pulmonary tuberculosis patients in six rural districts of Burkina Faso. Out-of-pocket expenses (direct costs) associated with TB were collected according to the different stages of their healthcare pathway. Results Median direct cost associated with TB was US$101 (n = 229) (i.e. 2.8 months of household income). Respectively 72% of patients incurred direct costs during the pre-diagnosis stage (i.e. self-medication, travel, traditional healers' services), 95% during the diagnosis process (i.e. user fees, travel costs to various providers, extra sputum smears microscopy and chest radiology), 68% during the intensive treatment (i.e. medical and travel costs) and 50% during the continuation treatment (i.e. medical and travel costs). For the diagnosis stage, median direct costs already amounted to 35% of overall direct costs. Conclusions The patient care pathway analysis in rural Burkina Faso showed substantial direct costs and healthcare system delay within a “free care” policy for TB diagnosis and treatment. Whether in terms of redefining the free TB package or rationalizing the care pathway, serious efforts must be undertaken to make “free” health care more affordable for the patients. Locally relevant for TB, this case-study in Burkina Faso has a real potential to document how health programs' weaknesses can be identified and solved. PMID:23451079

  14. Enhanced Tuberculosis Infection Treatment Outcomes after Implementation of QuantiFERON®-Gold Testing

    PubMed Central

    Crossa, Aldo; Kessler, Jason; Harris, Tiffany G.

    2015-01-01

    Background Use of the tuberculin skin test (TST) for diagnosis of latent tuberculosis infection (LTBI) among individuals who received the Bacille Calmette-Guérin (BCG) vaccine is complicated by its potential cross-reaction with TST antigens which may cause false-positive results and lead to patient and physician reluctance to initiate LTBI treatment. QuantiFERON®-TB Gold (QFT-G) lacks this cross-reaction. We sought to study the impact of implementing QFT-G testing in 2006 on LTBI treatment initiation and completion at NYC chest clinics. Methods QFT-G results from 10/2006–12/2008 in NYC Department of Health and Mental Hygiene chest clinics were obtained from the electronic medical record system. The proportions of patients who initiated and completed treatment among patients tested with QFT-G were compared to those tested with TST from 10/2004–9/2006. Results Among 36,167 patients tested with QFT-G, 2,300 (6%) tested positive, 33,327 (93%) tested negative, and 540 (1%) had an indeterminate result. Among those who had a positive QFT-G test and deemed eligible, 985 (80%) initiated LTBI treatment and 490 (40%) completed treatment. Historically, among patients tested with TST, 7,073 (19%) tested positive (p<0.0001 compared to QFT-G); 3,182 (79%) of those eligible initiated LTBI treatment and 1,210 (30%) completed treatment (p<0.0001 compared to QFT-G). Conclusions QFT-G implementation increased the proportion of patients completing LTBI treatment. Additional studies are needed in more settings to determine whether using QFT-G leads to a sustained increase in treatment completion. PMID:26371760

  15. Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis.

    PubMed

    Chien, Jung-Yien; Chien, Shun-Tien; Chiu, Wei-Yih; Yu, Chong-Jen; Hsueh, Po-Ren

    2016-08-01

    It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were included in the study. Among the 81 patients with OFX-resistant MDR-TB, 50 (61.7%) were successfully treated and 31 (38.3%) had unfavorable outcomes, including treatment failure (n = 25; 30.9%), loss to follow-up (n = 2; 2.5%), and death (n = 4; 4.9%). Patients treated with MFX had a significantly higher rate of treatment success (77.3% versus 43.2%; odds ratio [OR] = 4.46, 95% confidence interval [CI] = 1.710 to 11.646, P = 0.002) than patients not treated with MFX, especially among those infected with MFX-susceptible isolates (40.7%) or isolates with low-level resistance to MFX (28.4%). Multivariate logistic regression analysis showed that treatment with MFX (adjusted odds ratio = 6.54, 95% CI = 1.44 to 29.59, P = 0.015) was the only independent factor associated with treatment success. Mutation at codon 94 in the gyrA gene was the most frequent mutation (68.0%) associated with high-level MFX resistance. Multivariate Cox proportional hazards regression analysis showed that treatment with MFX was also an independent factor associated with early culture conversion (hazard ratio = 3.12, 95% CI = 1.48 to 6.54, P = 0.003). Our results show that a significant proportion of OFX-resistant MDR-TB isolates were susceptible or had low-level resistance to MFX, indicating that patients with OFX-resistant MDR-TB benefit from treatment with MFX. PMID:27216062

  16. [Multifocal tuberculosis in immunocompetent patients].

    PubMed

    Rezgui, Amel; Fredj, Fatma Ben; Mzabi, Anis; Karmani, Monia; Laouani, Chadia

    2016-01-01

    Multifocal tuberculosis is defined as the presence of lesions affecting at least two extrapulmonary sites, with or without pulmonary involvement. This retrospective study of 10 cases aims to investigate the clinical and evolutionary characteristics of multifocal tuberculosis. It included 41 cases with tuberculosis collected between 1999 and 2013. Ten patients had multifocal tuberculosis (24%): 9 women and 1 man, the average age was 50 years (30-68 years). Our patients were correctly BCG vaccinated. The evaluation of immunodepression was negative in all patients. 7 cases had lymph node tuberculosis, 3 cases digestive tuberculosis, 2 cases pericardial tuberculosis, 2 cases osteoarticular tuberculosis, 1 case brain tuberculosis, 2 cases urinary tuberculosis, 4 cases urogenital tuberculosis, 1 case adrenal tuberculosis, 1 case cutaneous and 1 case muscle tuberculosis. All patients received anti-tuberculosis treatment for a mean duration of 10 months, with good evolution. Multifocal tuberculosis is difficult to diagnose. It can affect immunocompetent patients but often has good prognosis. Anti-tuberculosis therapy must be initiated as soon as possible to avoid sequelae. PMID:27583077

  17. Spinal Tuberculosis

    PubMed Central

    Ekinci, Safak; Tatar, Oner; Akpancar, Serkan; Bilgic, Serkan; Ersen, Omer

    2015-01-01

    Spinal tuberculosis (TB) is a significant form of TB, causing spinal deformity and paralysis. Early diagnosis and treatment are crucial for avoiding multivertebral destruction and are critical for improving outcomes in spinal TB. We believe that appropriate treatment method should be implemented at the early stage of this disease and that the Gulhane Askeri Tıp Akademisi classification system can be considered a practical guide for spinal TB treatment planning in all countries. PMID:26609247

  18. Urinary tuberculosis

    PubMed Central

    Riddle, P. R.

    1971-01-01

    The present incidence, clinical features and classification of urinary tuberculosis are discussed. Chemotherapy is the mainstay of treatment. The indications for surgical intervention are reviewed and procedures briefly described. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:5169185

  19. Impacts of 12-dose regimen for latent tuberculosis infection: Treatment completion rate and cost-effectiveness in Taiwan.

    PubMed

    Huang, Yi-Wen; Yang, Shun-Fa; Yeh, Yen-Po; Tsao, Thomas Chang-Yao; Tsao, Shih-Ming

    2016-08-01

    Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P <0.001). The cost of 3HP and 9H was US$261.24 and US$717.3, respectively. The cost-effectiveness ratio with isoniazid for 9 months was US$ 15392/avoided 1 case of tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment

  20. Phytotherapeutic Information on Plants Used for the Treatment of Tuberculosis in Eastern Cape Province, South Africa

    PubMed Central

    Lawal, I. O.; Grierson, D. S.; Afolayan, A. J.

    2014-01-01

    The current rate of deforestation in Africa constitutes a serious danger to the future of medicinal plants on this continent. Conservation of these medicinal plants in the field and the scientific documentation of our knowledge about them are therefore crucial. An ethnobotanical survey of plants used for the treatment of tuberculosis (TB) was carried out in selected areas of the Eastern Cape, South Africa. These areas were Hala, Ncera, Sheshegu, and Gquamashe, all within the Nkonkobe Municipality. One hundred informants were interviewed. The survey included the identification of scientific and vernacular names of the plants used for treatment of TB as well as the methods of preparation and administration, the part used, dosage, and duration of treatment. The survey revealed 30 plants belonging to 21 families which are commonly used by traditional healers for the treatment of TB and associated diseases. Of these plants Clausena anisata, Haemanthus albiflos, and Artemisia afra were the most cited. The leaves were the most common part used in the medicinal preparations. Our findings are discussed in relation to the importance of the documentation of medicinal plants. PMID:24864158

  1. The burden and treatment outcomes of extra-pulmonary tuberculosis in Bhutan

    PubMed Central

    Harries, A. D.; Malhotra, S.; Wangchuk, D.; Dophu, U.; Dorji, T.; Dendup, T.

    2013-01-01

    Setting: All tuberculosis (TB) registration sites in Bhutan. Design: Cross-sectional study involving a retrospective review of TB registers and TB treatment cards. Objectives: To determine: 1) the number and proportion of all TB cases registered as extra-pulmonary TB (EPTB) from 2001 to 2010, 2) the age and sex of the patients and the categories and types of EPTB registered in 2010, and 3) their treatment outcomes. Results: The proportion of all TB cases registered as EPTB over a period of 10 years varied from 30% to 40%. In 2010, 505 patients were registered with EPTB, of whom 50% were male, 21% were children, and 96% were new EPTB cases. TB lymph node enlargement and pleural effusion were the two most common types of EPTB, accounting for 67%, followed by abdominal TB and spinal/bone/kidney disease. The overall treatment success rate was 90%, and was generally similar with respect to sex, age and different types of EPTB. Conclusion: Bhutan has a high proportion of patients registered as having EPTB, for whom treatment outcomes are satisfactory. Further work is needed to better understand how EPTB is diagnosed throughout the country. PMID:26392994

  2. Phytotherapeutic information on plants used for the treatment of tuberculosis in eastern cape province, South Africa.

    PubMed

    Lawal, I O; Grierson, D S; Afolayan, A J

    2014-01-01

    The current rate of deforestation in Africa constitutes a serious danger to the future of medicinal plants on this continent. Conservation of these medicinal plants in the field and the scientific documentation of our knowledge about them are therefore crucial. An ethnobotanical survey of plants used for the treatment of tuberculosis (TB) was carried out in selected areas of the Eastern Cape, South Africa. These areas were Hala, Ncera, Sheshegu, and Gquamashe, all within the Nkonkobe Municipality. One hundred informants were interviewed. The survey included the identification of scientific and vernacular names of the plants used for treatment of TB as well as the methods of preparation and administration, the part used, dosage, and duration of treatment. The survey revealed 30 plants belonging to 21 families which are commonly used by traditional healers for the treatment of TB and associated diseases. Of these plants Clausena anisata, Haemanthus albiflos, and Artemisia afra were the most cited. The leaves were the most common part used in the medicinal preparations. Our findings are discussed in relation to the importance of the documentation of medicinal plants. PMID:24864158

  3. Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Treatment among Co-Infected Persons in South Africa, 2008–2010

    PubMed Central

    Webb Mazinyo, Ernesha; Kim, Lindsay; Masuku, Sikhethiwe; Lancaster, Joey L.; Odendaal, Ronel; Uys, Margot; Podewils, Laura Jean; Van der Walt, Martie L.

    2016-01-01

    Background Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. Methods A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008–31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence. Results Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). Conclusions The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment. PMID:27442440

  4. Intermittent Versus Daily Pulmonary Tuberculosis Treatment Regimens: A Meta-Analysis

    PubMed Central

    Kasozi, Samuel; Clark, Justin; Doi, Suhail A. R.

    2015-01-01

    Background Several systematic reviews suggest that intermittent pulmonary tuberculosis (TB) chemotherapy is effective, but intensity (daily versus intermittent) and duration of rifampicin use (intensive phase only versus both phases) have not been distinguished. In addition, the various outcomes (success, failure, relapse, and default) have only selectively been evaluated. Methods We conducted a meta-analysis of proportions using all four outcomes as multi-category proportions to examine the effectiveness of WHO category 1 TB treatment regimens. Database searches of studies reporting treatment outcomes of HIV negative subjects were included and stratified by intensity of therapy and duration of rifampicin therapy. Using a bias-adjusted statistical model, we pooled proportions of the four treatment outcome categories using a method that handles multi-category proportions. Results A total of 27 studies comprising of 48 data sets with 10,624 participants were studied. Overall, treatment success was similar among patients treated with intermittent (I/I) (88%) (95% CI, 81–92) and daily (D/D) (90%) (95% CI, 84–95) regimens. Default was significantly less with I/I (0%) (95% CI, 0–2) compared to D/D regimens (5%) (95% CI, 1–9). Nevertheless, I/I relapse rates (7%) (95% CI, 3–11) were higher than D/D relapse rates (1%) (95% CI, 0–3). Conclusion Treatment regimens that are offered completely intermittently versus completely daily are associated with a trade-off between treatment relapse and treatment default. There is a possibility that I/I regimens can be improved by increasing treatment duration, and this needs to be urgently addressed by future studies. PMID:26056374

  5. Childhood tuberculosis.

    PubMed

    Jacobs, R F; Eisenach, K D

    1993-01-01

    The dramatic resurgence and increase in the total number of cases of tuberculous infection and disease in children is alarming in the United States. With poverty, poor access to health care, overcrowding (predominantly in inner-city areas), and an increase in immigration from areas with high endemic rates of tuberculosis, the problem in children will continue to increase. If the impact of coinfection with HIV and M. tuberculosis becomes significant, as it has in adults in the United States, this increase in the total number of cases of tuberculous disease could be staggering. The impact of multiple drug-resistant strains of M. tuberculosis and the current crises in availability of effective antituberculous drugs will need to undergo basic and clinical research. Although the possibility for eradication of M. tuberculosis as a human pathogen in the United States still exists, clinicians must reeducate themselves regarding the epidemiology, pathophysiology, diagnostic work-up, and effective treatment of children with tuberculosis in the current situation of increasing tuberculous disease and resistant organisms in children. PMID:8217004

  6. Risk Factors Associated with Default from Multi- and Extensively Drug-Resistant Tuberculosis Treatment, Uzbekistan: A Retrospective Cohort Analysis

    PubMed Central

    Lalor, Maeve K.; Greig, Jane; Allamuratova, Sholpan; Althomsons, Sandy; Tigay, Zinaida; Khaemraev, Atadjan; Braker, Kai; Telnov, Oleksander; du Cros, Philipp

    2013-01-01

    Background The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010. Methods A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression. Results 20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6–9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31–0.86), previous default (2.38, 1.09–5.24) and age >45 years (1.77, 1.10–2.87). The default rate was 14% (42/294) for patients enrolled 2003–2006 and 24% (100/416) for 2007–2008 enrolments (p = 0.001). Conclusions Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease

  7. Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis.

    PubMed

    Mzinza, David T; Sloan, Derek J; Jambo, Kondwani C; Shani, Doris; Kamdolozi, Mercy; Wilkinson, Katalin A; Wilkinson, Robert J; Davies, Geraint R; Heyderman, Robert S; Mwandumba, Henry C

    2015-07-01

    In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings. PMID:26051653

  8. Epidemiology of tuberculosis and leprosy, Sabah, Malaysia.

    PubMed

    Dony, Jiloris F; Ahmad, Jamaliah; Khen Tiong, Yap

    2004-01-01

    The objectives in this epidemiology review are to measure and report the extent of morbidity and mortality due to tuberculosis (TB), the proportion of new sputum smear positive cases in districts and the status of cohort analysis as of 1999. As for leprosy, the main objective is to determine morbidity and the treatment outcomes of Multiple Drug Therapy (MDT). Based on the results obtained, a comprehensive action plan for prevention, control and monitoring of tuberculosis and leprosy cases and patients is being produced and implemented throughout the state. The analysis concentrated on patients diagnosed at all out-patient units and admitted in all of the state's hospitals. The patient particulars were recorded using a standardized format based on TB and Leprosy Health Management Information System (TB HMIS). TB was the second highest by notification of communicable diseases in Malaysia in 2001. 29% or about one-third of the national TB cases are from Sabah. However, it has been noted that there was an average decline of 2.6% in annual notification since 10 years ago to date. There was also a reduction of 11.4% in 2001 as compared to annual notification in 2000. Immigrants contribute more than 24% in detection of new cases since 1990. Treatment success rate in term of completion of treatment to date is 82%. Mortality rate has steadily declined from 14 deaths to 7 deaths per 100,000 population. Leprosy in Sabah also contributes to 30% of the yearly total caseload of Malaysia and has the highest notification rate of 2 per every 100,000 population as compared to other states. The average registered leprosy cases over the past 5 years are 239 cases and the prevalence rate is 0.7/10,000 population. The state has successfully achieved its goal to decrease leprosy as per the World Health Organization (WHO) goal of yearly overall prevalence rate of less than 1 case for every 10,000 population. However, the districts of Kudat, Tawau, Lahad Datu, Kota Kinabalu and Semporna

  9. Patients with Tuberculosis Have a Dysfunctional Circulating B-Cell Compartment, Which Normalizes following Successful Treatment

    PubMed Central

    del Nonno, Franca; Baiocchini, Andrea; Petrone, Linda; Vanini, Valentina; Smits, Hermelijn H.; Palmieri, Fabrizio; Goletti, Delia; Ottenhoff, Tom H. M.

    2016-01-01

    B-cells not only produce immunoglobulins and present antigens to T-cells, but also additional key roles in the immune system. Current knowledge on the role of B-cells in infections caused by intracellular bacteria is fragmentary and contradictory. We therefore analysed the phenotypical and functional properties of B-cells during infection and disease caused by Mycobacterium tuberculosis (Mtb), the bacillus causing tuberculosis (TB), and included individuals with latent TB infection (LTBI), active TB, individuals treated successfully for TB, and healthy controls. Patients with active or treated TB disease had an increased proportion of antibodies reactive with mycobacteria. Patients with active TB had reduced circulating B-cell frequencies, whereas only minor increases in B-cells were detected in the lungs of individuals deceased from TB. Both active TB patients and individuals with LTBI had increased relative fractions of B-cells with an atypical phenotype. Importantly, these B-cells displayed impaired proliferation, immunoglobulin- and cytokine- production. These defects disappeared upon successful treatment. Moreover, T-cell activity was strongest in individuals successfully treated for TB, compared to active TB patients and LTBI subjects, and was dependent on the presence of functionally competent B-cells as shown by cellular depletion experiments. Thus, our results reveal that general B-cell function is impaired during active TB and LTBI, and that this B-cell dysfunction compromises cellular host immunity during Mtb infection. These new insights may provide novel strategies for correcting Mtb infection-induced immune dysfunction towards restored protective immunity. PMID:27304615

  10. [Pharyngeal tuberculosis: Case report].

    PubMed

    Spini, Roxana Gabriela; Bordino, Lucas; Cohen, Daniela; Martins, Andrea; Ramírez, Zaida; González, Norma E

    2015-08-01

    Pharyngeal tuberculosis is a rare extrapulmonary manifestation. In Argentina, the number of cases of tuberculosis reported in children under 19 years in 2012 was 1752. Only 12.15% had extrapulmonary manifestation. A case of a 17 year old girl with pharyngeal tuberculosis is reported. The patient presented intermittent fever and swallowing pain for 6 months, without response to conventional antibiotic treatment. Chest X-ray showedbilateral micronodular infiltrate, so hospitalization was decided to study and treat. The sputum examination for acid-fast resistant bacilli was positive and treatment with four antituberculous drugs was started, with good evolution and disappearance of symptoms. Diagnostic confirmation with the isolation of Mycobacterium tuberculosis in sputum culture was obtained. The main symptoms of pharyngeal tuberculosis are sore throat and difficulty in swallowing of long evolution. It is important to consider tuberculosis as differential diagnosis in patients with chronic pharyngitis unresponsive to conventional treatment. PMID:26172025

  11. Diagnosis and Treatment of Childhood Pulmonary Tuberculosis: A Cross-Sectional Study of Practices among Paediatricians in Private Sector, Mumbai

    PubMed Central

    Tauro, Carolyn Kavita; Gawde, Nilesh Chandrakant

    2015-01-01

    Majority of children with tuberculosis are treated in private sector in India with no available data on management practices. The study assessed diagnostic and treatment practices related to childhood pulmonary tuberculosis among paediatricians in Mumbai's private sector in comparison with International Standards for Tuberculosis Care (ISTC) 2009. In this cross-sectional study, 64 paediatricians from private sector filled self-administered questionnaires. Cough was reported as a symptom of childhood TB by 77.8% of respondents. 38.1% request sputum smear or culture for diagnosis and fewer (32.8%) use it for patients positive on chest radiographs and 32.8% induce sputum for those unable to produce it. Sputum negative TB suspect is always tested with X-ray or tuberculin skin test. 61.4% prescribe regimen as recommended in ISTC and all monitor progress to treatment clinically. Drug-resistance at beginning of treatment is suspected for child in contact with a drug-resistant patient (67.7%) and with prior history of antitubercular treatment (12.9%). About half of them (48%) request drug-resistance test for rifampicin in case of nonresponse after two to three months of therapy and regimen prescribed by 41.7% for multidrug-resistant TB was as per ISTC. The study highlights inappropriate diagnostic and treatment practices for managing childhood pulmonary TB among paediatricians in private sector. PMID:26379705

  12. An ontology for factors affecting tuberculosis treatment adherence behavior in sub-Saharan Africa

    PubMed Central

    Ogundele, Olukunle Ayodeji; Moodley, Deshendran; Pillay, Anban W; Seebregts, Christopher J

    2016-01-01

    Purpose Adherence behavior is a complex phenomenon influenced by diverse personal, cultural, and socioeconomic factors that may vary between communities in different regions. Understanding the factors that influence adherence behavior is essential in predicting which individuals and communities are at risk of nonadherence. This is necessary for supporting resource allocation and intervention planning in disease control programs. Currently, there is no known concrete and unambiguous computational representation of factors that influence tuberculosis (TB) treatment adherence behavior that is useful for prediction. This study developed a computer-based conceptual model for capturing and structuring knowledge about the factors that influence TB treatment adherence behavior in sub-Saharan Africa (SSA). Methods An extensive review of existing categorization systems in the literature was used to develop a conceptual model that captured scientific knowledge about TB adherence behavior in SSA. The model was formalized as an ontology using the web ontology language. The ontology was then evaluated for its comprehensiveness and applicability in building predictive models. Conclusion The outcome of the study is a novel ontology-based approach for curating and structuring scientific knowledge of adherence behavior in patients with TB in SSA. The ontology takes an evidence-based approach by explicitly linking factors to published clinical studies. Factors are structured around five dimensions: factor type, type of effect, regional variation, cross-dependencies between factors, and treatment phase. The ontology is flexible and extendable and provides new insights into the nature of and interrelationship between factors that influence TB adherence. PMID:27175067

  13. Tuberculosis notifications, characteristics and treatment outcomes: urban vs. rural Solomon Islands, 2000–2011

    PubMed Central

    Hill, P. C.; Bissell, K.; Harries, A. D.; Viney, K.; Gounder, S.

    2014-01-01

    Setting: All provincial tuberculosis (TB) management units in the Solomon Islands. Objective: To compare TB notifications, characteristics and treatment outcomes in urban vs. rural areas. Design: A retrospective descriptive cohort study involving record review and data extraction from provincial TB and laboratory registers and treatment charts from 2000 to 2011. Results: Of 4137 TB cases notified, 1364 (33%) were from urban and 3227 (67%) from rural areas. Notification rates per year of study were consistently higher in urban areas (104–150 per 100 000 population) than in rural areas (49–70/100 000). Cases in rural areas were more likely to have smear-negative pulmonary TB and less likely to have extra-pulmonary TB (P < 0.001). TB cases in rural areas were more likely to die from TB than those from urban areas (3.2% vs. 5.9%). In contrast, TB cases in rural areas were less likely to default (2.8% vs. 1.8%). Conclusion: TB notification rates were much higher in urban than in rural areas in the Solomon Islands. Rural patients are more likely to die from the disease but are slightly less likely to default. Further research is required to explore the possibility of under-reporting in rural areas and to improve treatment outcomes. PMID:26477283

  14. Tuberculosis situation among tribal population of Car Nicobar, India, 15 years after intensive tuberculosis control project and implementation of a national tuberculosis programme.

    PubMed Central

    Murhekar, M. V.; Kolappan, C.; Gopi, P. G.; Chakraborty, A. K.; Sehgal, S. C.

    2004-01-01

    OBJECTIVE: To assess the tuberculosis (TB) situation in the tribal community of Car Nicobar island 15 years after the national TB programme was implemented in this area after an intensive phase of TB control in 1986. METHODS: The entire population of Car Nicobar was enumerated through a house-to-house survey. Children aged <14 years were tuberculin tested and read for reaction sizes. Individuals aged >15 years were asked about the presence of chest symptoms (cough, chest pain, and unexplained fever for two weeks or longer and haemoptysis), and sputum samples were collected from patients with chest symptoms. Sputum samples were examined for presence of acid-fast bacilli. FINDINGS: Among the 4,543 children enumerated, 4,351 (95.8%) were tuberculin tested and read. Of the 981 children without bacille Calmette-Guerin scars, 161 (16.4%) were infected with TB. A total of 77 cases who were smear-positive for TB were detected from among 10,570 people aged >15 years; the observed smear-positive case prevalence was 728.5 per 100,000. The standardized prevalence of TB infection, annual risk of TB infection, and prevalence of cases smear-positive for TB were 17.0%, 2.5%, and 735.3 per 100,000, respectively. CONCLUSION: The prevalence of TB infection and smear-positive cases of TB increased significantly between 1986 and 2002. Such escalation took place despite the implementation of the national TB programme on this island, which was preceded by a set of special anti-TB measures that resulted in sputum conversion in a substantially large proportion of the smear-positive cases prevalent in the community. The most likely reason for the increase seems to be the absence of a district TB programme with enough efficiency to sustain the gains made from the one-time initial phase of special anti-TB measures. High risk of transmission of TB infection currently observed on this island calls for a drastic and sustained improvement in TB control measures. PMID:15640919

  15. Evaluation of tuberculosis treatment results in Italy, report 1998. Tuberculosis section of the National AIPO Study Group on Infectious Disease and the SMIRA Group.

    PubMed

    Centis, R; Ianni, A; Migliori, G B

    2000-08-01

    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 representative network of TB units nationwide, 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 1998. The number of TB cases reported was 1162 (61.7% males; 28.2% immigrants), 888 (76.6%) being new cases. Of these cases, 1,001 (86.4%) were pulmonary, 132 (11.4%) extrapulmonary and 26 (2.2%) both pulmonary and extrapulmonary. The main risk factors for TB were a history of recent contact, diabetes and alcohol abuse among native Italians and human immunodeficiency virus-seropositive status and history of recent contact among immigrants. The majority of immigrants were from Africa and South America, and had been in Italy > 24 months before diagnosis of TB. Forty-seven per cent (552 of 1,162) of patients had a positive direct sputum smear examination for alcohol acidfast bacilli; 30% were resistant to any drug (combined monoresistance (the sum of primary and acquired drug resistance) to rifampicin 2.3%; combined multidrug resistance 11.4%). In 97% of cases, the duration of treatment was < 12 months. The overall success rate (cured plus treatment completed excluding transferred out from the denominator) was 83%. A significantly higher percentage of deaths was found in native Italians (being age-related; p < 0.001), whereas immigrants had a higher default rate. PMID:11057082

  16. Gender differences in treatment outcomes of tuberculosis patients in Taiwan: a prospective observational study.

    PubMed

    Feng, J-Y; Huang, S-F; Ting, W-Y; Chen, Y-C; Lin, Y-Y; Huang, R-M; Lin, C-H; Hwang, J-J; Lee, J-J; Yu, M-C; Yu, K-W; Lee, Y-C; Su, W-J

    2012-09-01

    Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50 ~ 60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12-3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management. PMID:22734962

  17. A Step toward Tuberculosis Elimination in a Low-Incidence Country: Successful Diagnosis and Treatment of Latent Tuberculosis Infection in a Refugee Clinic.

    PubMed

    Rennert-May, Elissa; Hansen, Elisabeth; Zadeh, Toktam; Krinke, Valerie; Houston, Stan; Cooper, Ryan

    2016-01-01

    Objectives. Approximately 65 percent of tuberculosis (TB) cases in Canada each year occur from reactivation in foreign-born individuals. Refugees are at high risk after immigration. Routine screening of this population for latent TB infection (LTBI) is generally considered infeasible. We evaluated the outcome of LTBI screening and treatment amongst refugees. Methods. Government-sponsored refugees in Edmonton are seen at the New Canadians' Clinic and screened for TB and LTBI. We reviewed records of patients between 2009 and 2011. Completeness of initial assessment, diagnosis of latent infection, and completion of LTBI treatment were evaluated. Treatment for LTBI was offered when patients had a positive Tuberculin Skin Test (TST) and risk factors for progression to TB. An Interferon-Gamma Release Assay (IGRA) was performed on all other TST positives; treatment is only offered if it was positive. Results. 949 refugees were evaluated. 746 TSTs were read, with 265 positive individuals. IGRA testing was performed in 203 TST positive individuals without other TB risk factors; 110 were positive. LTBI treatment was offered to 147 of 151 eligible patients, 141 accepted, and 103 completed a treatment course. Conclusion. We observed high proportions of patient retention, completion of investigations, and treatment. This care model promises to be a component of effective TB prevention in this high-risk population. PMID:27445565

  18. Design and construction of a DNA origami drug delivery system based on MPT64 antibody aptamer for tuberculosis treatment

    PubMed Central

    Ranjbar, Reza; Hafezi-Moghadam, Mohammad Sadegh

    2016-01-01

    Introduction With all of the developments on infectious diseases, tuberculosis (TB) remains a cause of death among people. One of the most promising assembly techniques in nano-technology is “scaffolded DNA origami” to design and construct a nano-scale drug delivery system. Because of the global health problems of tuberculosis, the development of potent new anti-tuberculosis drug delivery system without cross-resistance with known anti-mycobacterial agents is urgently needed. The aim of this study was to design a nano-scale drug delivery system for TB treatment using the DNA origami method Methods In this study, we presented an experimental research on a DNA drug delivery system for treating Tuberculosis. TEM images were visualized with an FEI Tecnai T12 BioTWIN at 120 kV. The model was designed by caDNAno software and computational prediction of the 3D solution shape and its flexibility was calculated with a CanDo server. Results Synthesizing the product was imaged using transmission electron microscopy after negative-staining by uranyl formate. Conclusion We constructed a multilayer 3D DNA nanostructure system by designing square lattice geometry with the scaffolded-DNA-origami method. With changes in the lock and key sequences, we recommend that this system be used for other infectious diseases to target the pathogenic bacteria. PMID:27053991

  19. Cost-effectiveness of rifampin for 4 months and isoniazid for 9 months in the treatment of tuberculosis infection.

    PubMed

    Pina, J M; Clotet, L; Ferrer, A; Sala, M R; Garrido, P; Salleras, L; Domínguez, A

    2013-05-01

    The purpose of this study was to evaluate the cost-effectiveness of the strategy of controlling the contacts of tuberculosis patients with latent tuberculosis infection by means of treatment with rifampin for 4 months or isoniazid for 9 months. The cost was the sum of the cost of treating latent tuberculosis infection in all contacts plus the cost of treating tuberculosis in whom the disease was not avoided. The effectiveness was expressed as cases avoided. The efficacy adopted was 90 % for rifampin for 4 months and 93 % for isoniazid for 9 months. We carried out a sensitivity analysis for efficacies of rifampin for 4 months of 80 %, 75 %, 69 % and 65 %. Of the 1,002 patients studied, 139 were treated with rifampin for 4 months and 863 were treated with isoniazid for 9 months. The cost-effectiveness was 436,842.83/50 cases avoided with rifampin for 4 months and 692,164.42/40 cases avoided with isoniazid for 9 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies of 75 % or greater. The cost-effectiveness analysis favoured the use of rifampin for 4 months when its efficacy was 75 % or greater. PMID:23238684

  20. Surgical treatment of selected patients with multilevel contiguous thoracolumbar spinal tuberculosis by only posterior instrumentation without any bone fusion

    PubMed Central

    Shen, Xiongjie; Huang, Xiangwang; Xiao, Sheng; Liu, Hongzhe; Zhang, Yi; Xiang, Tiecheng; Wang, Guoping; Sheng, Bin; Huang, Shu; Liu, Xiangyang

    2015-01-01

    The retrospective clinical study is to determine the feasibility and efficacy of surgical management of multilevel contiguous thoracolumbar spinal tuberculosis (MCTLST) by only posterior instrumentation without posterior or anterior bone fusion and without anterior fixation in the study of eleven selected cases. Eleven selected cases with MCTLST were treated with combined posterior instrumentation and debridement and/or decompression without any bone fusion. The mean follow-up was 33.1 months (range 20-48 months). The kyphosis angle ranged from 9.2 to 40.4° before operation, 27.8° in average. The American Spinal Injury Association (ASIA) score system was used to evaluate the neurological deficits and erythrocytesedimentationrate (ESR) used to judge the activity of tuberculosis, which were collected at certain time. Spinal tuberculosis (STB) was completely cured in all eleven patients. There was no recurrent tuberculosis infection. The postoperative kyphosis angle was 7.1° to 12.5°, 9.6° in average and there was no significant loss of the correction at the final follow-up. Solid fusion was achieved in all cases. Neurological condition in all patients was improved after surgery. In conclusions, combined posterior instrumentation and debridement and/or decompression without any bone fusion can be a feasible and effective method in treatment of patients with MCTLST. However, the strict selection of patients was the critical of the surgery success. PMID:26770474

  1. Use of Lot Quality Assurance Sampling to Ascertain Levels of Drug Resistant Tuberculosis in Western Kenya

    PubMed Central

    Cohen, Ted; Zignol, Matteo; Nyakan, Edwin; Hedt-Gauthier, Bethany L.; Gardner, Adrian; Kamle, Lydia; Injera, Wilfred; Carter, E. Jane

    2016-01-01

    Objective To classify the prevalence of multi-drug resistant tuberculosis (MDR-TB) in two different geographic settings in western Kenya using the Lot Quality Assurance Sampling (LQAS) methodology. Design The prevalence of drug resistance was classified among treatment-naïve smear positive TB patients in two settings, one rural and one urban. These regions were classified as having high or low prevalence of MDR-TB according to a static, two-way LQAS sampling plan selected to classify high resistance regions at greater than 5% resistance and low resistance regions at less than 1% resistance. Results This study classified both the urban and rural settings as having low levels of TB drug resistance. Out of the 105 patients screened in each setting, two patients were diagnosed with MDR-TB in the urban setting and one patient was diagnosed with MDR-TB in the rural setting. An additional 27 patients were diagnosed with a variety of mono- and poly- resistant strains. Conclusion Further drug resistance surveillance using LQAS may help identify the levels and geographical distribution of drug resistance in Kenya and may have applications in other countries in the African Region facing similar resource constraints. PMID:27167381

  2. DOT associated with reduced all-cause mortality among tuberculosis patients in Taipei, Taiwan, 2006–2008

    PubMed Central

    Yen, Y-F.; Rodwell, T. C.; Yen, M-Y.; Shih, H-C.; Hu, B-S.; Li, L-H.; Shie, Y-H.; Chuang, P.; Garfein, R. S.

    2012-01-01

    OBJECTIVE To determine whether patients receiving directly observed treatment (DOT) had lower all-cause mortality than those treated with self-administered treatment (SAT) and to identify factors associated with mortality among tuberculosis (TB) patients. DESIGN All TB patients in Taipei, Taiwan, diagnosed between 2006 and 2008 were included in a retrospective cohort study. RESULTS Among 3624 TB patients, 45.5% received DOT, which was disproptionately offered to older patients and those with more underlying illness and severe TB disease. After controlling for patient sociodemographic factors, clinical findings and underlying comorbidities, the odds of death was 40% lower (aOR 0.60, 95%CI 0.5–0.8) among patients treated with DOT than those on SAT. After adjusting for DOT, independent predictors of death included non-Taiwan birth, increasing age, male, unemployment, end-stage renal disease requiring dialysis, malignancy, acid-fast bacilli smear positivity and pleural effusion. CONCLUSION DOT was associated with lower all-cause mortality after controlling for confounding factors. DOT should be expanded in Taiwan to improve critical treatment outcomes among TB patients. PMID:22236917

  3. Factors Affecting Mortality and Treatment Completion of Tuberculosis Patients in Isfahan Province from 2006 to 2011

    PubMed Central

    Shahrezaei, Marzieh; Maracy, Mohammad Reza; Farid, Fariba

    2015-01-01

    Background: Regarding cases of infectious diseases tuberculosis (TB) is the most important cause of death and according to the DALY criteria, this disease has the seventh position in global disease ranking. In this study, we aim to determine the risk factors, which have a significant effect on the treatment completion and mortality of TB patients. Methods: This study is a retrospective cohort study. The sample is made up of registered TB patients in the Isfahan Province from 2006 to 2011. Information of the patients was collected from their files in health centers in the Isfahan Province. Variables such as age, sex, weight, nationality, residence, type of TB, imprisonment, human immunodeficiency virus, TB case were measured. Descriptive statistics (including frequency, percentage, mean and standard deviation) and statistical analysis (including Cox proportional hazard model) were used. Results: The result showed that imprisonment (hazard ratio [HR] = 4.76, P = 0.019), age (HR = 4.44, P = 0.001) and the TB case (HR = 2.73, P = 0.037) of pulmonary TB had significant impacts on mortality of the patients, also in the case of treatment completion, the TB case (HR = 0.34, P < 0.001) proved to have a significant impact on completion of the treatment. Type of extra-pulmonary TB in extra-pulmonary TB patients also had an effect on treatment completion. Conclusions: We can conclude that factors such as age, imprisonment, TB case and type of extra-pulmonary TB are effective on the treatment completion and mortality of the patients. It may be useful for policy makers to make more control of high-risk patients. PMID:26445638

  4. Delays in diagnosis and treatment of pulmonary tuberculosis in Wakiso and Mukono districts, Uganda

    PubMed Central

    2014-01-01

    Background Delay in tuberculosis (TB) diagnosis may worsen the disease and increase TB transmission. Therefore, timely diagnosis and treatment is critical in TB control. We aimed to assess the treatment delay of pulmonary TB and its determinants in two Ugandan districts where TB infection control (TBIC) guidelines were formerly implemented. Methods A facility based cross-sectional study was conducted in Mukono and Wakiso districts. Adult pulmonary TB patients within three months of initiating treatment were included in the study. Delays were categorized into unacceptable patient delay (more than 3 weeks from the onset of cough and the first consultation with a health care provider), health service (more than one week from the first consultation to the initiation of TB treatment) and total delay (more than 4 weeks since the onset of cough). The prevalences as well as predictors for the three delays were determined. Results We enrolled 158 sputum positive patients. Unacceptable patient delay was noted in 91 (58%) patients, a health service delay in 140 (88%) patients and a total delay in 140 (90%) patients. An independent predictor for patient delay was male gender (p < 0.001). First visiting a non-public health facility (p = 0.001) was an independent predictor of health service delay. Conclusion There is still a significant TB diagnosis and treatment delay in Uganda. Most of the delay was caused by health system delay in the non-public health care sector. There is need for TB advocacy in the community, training of health workers in TBIC and strengthening public-private partnerships in TB control. PMID:24916459

  5. Aptamer-based Proteomic Signature of Intensive Phase Treatment Response in Pulmonary Tuberculosis

    PubMed Central

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

    2014-01-01

    Background New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing. Methods In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial. Results We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. Markers noted to have differential changes between responders and slow-responders included nectin-like protein 2, EphA1 (Ephrin type-A receptor 1), gp130, CNDP1, TGF-b RIII, MRC2, ADAM9, and CDON. A logistic regression model combining markers associated with 8-week culture status revealed an ROC curve with AUC=0.96, sensitivity=0.95 and specificity=0.90. Additional markers showed differential changes between responders and slow-responders (nectin-like protein), or correlated with time-to-culture-conversion (KLRK1). Conclusions Serum proteins involved in the coagulation cascade, neutrophil activity, immunity, inflammation, and tissue remodeling were found to be associated with TB treatment response. A quantitative, non-culture based, five-marker signature predictive of 8-week culture status was identified in this pilot study. PMID:24629635

  6. Increased Complement C1q Level Marks Active Disease in Human Tuberculosis

    PubMed Central

    Zhang, Mingxia; Liu, Haiying; Zhang, Guoliang; Deng, Qunyi; Huang, Jian; Gao, Zhiliang; Zhou, Boping; Feng, Carl G.; Chen, Xinchun

    2014-01-01

    Background Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. Methods Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. Results C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. Conclusions C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy. PMID:24647646

  7. [The process of detection and treatment of cases of tuberculosis in a prison].

    PubMed

    Valença, Mariana Soares; Cezar-Vaz, Marta Regina; Brum, Clarice Brinck; Silva, Pedro Eduardo Almeida da

    2016-06-01

    This study seeks to analyze the process of detection and treatment of cases of tuberculosis (TB) in a prison in the south of Brazil. An active and passive search for TB was conducted to estimate the scale of TB in a prison with 764 inmates. In conjunction with the detection strategies and clinical follow-up of the 41 TB cases, participant observation and records in field diaries were performed, making it possible to analyze the scope and limitations of detection and treatment of cases of TB in prison. The development of search strategies is discussed along with the use of questionnaires to detect symptomatic cases, as well as the inadequacy of the clinical follow-up of TB cases, involvement of different workers and coordination between prison and health services. There is clear potential for the control of TB using an active search to induce the passive detection and screening for symptoms that - even skewed by the perceptions of inmates regarding symptoms of TB - enabled an increase in detection. The functional dynamics of prison life hamper the inclusion of health routines and can restrict actions to control TB and other diseases. In the process of control of TB in prisons, the feasibility of effective detection methods is as important as planning based on disease conditions, network services and workers involved. PMID:27383345

  8. Ethnomedical Knowledge of Plants Used for the Treatment of Tuberculosis in Johor, Malaysia.

    PubMed

    Sabran, Siti Fatimah; Mohamed, Maryati; Abu Bakar, Mohd Fadzelly

    2016-01-01

    This study documented ethnomedical knowledge of plants used for the treatment of tuberculosis (TB) and its related symptoms as practiced by the Jakun community of Kampung Peta, situated in Endau Rompin Johor National Park, Johor, Malaysia. Eight key informants were selected by snowball sampling technique and data about medicinal plants were collected by semistructured interviews, participatory observations, and focus group. Qualitative analysis was undertaken using thematic analysis. There were 23 species of plants (22 genera, 20 families) documented and herbarium specimens were deposited at the UTHM Herbarium. Dipterocarpus sublamellatus was recorded for the first time with ethnomedical uses while other species were previously reported. The qualitative approach employed in this study demonstrates the emic perspective in terms of perceptions on traditional herbal medicine, transfer of knowledge, significant taboos related with medicinal plants, and their conservation efforts. Local and biomedical terminology in treatment of TB showed substantial correspondence. The outcomes obtained in the study are worth being further investigated for conservation strategies and are worthy of verifying their ethnomedical claims scientifically. PMID:26881002

  9. Collaborative activities and treatment outcomes in patients with HIV-associated tuberculosis in Viet Nam

    PubMed Central

    Nhung, N. V.; Shewade, H. D.; Hoa, N. B.; Harries, A. D.

    2016-01-01

    Setting: The National Tuberculosis (TB) Programme in Viet Nam and Ho Chi Minh City (HCMC). Objectives: To determine 1) at national level between 2011 and 2013, the relationship between human immunodeficiency virus (HIV) testing, uptake of TB-HIV interventions and adverse treatment outcomes among TB-HIV patients; and 2) in HCMC in 2013, patient characteristics associated with adverse outcomes. Design: An ecological study reviewing aggregate nationwide data and a retrospective cohort review in HCMC. Results: Nationwide, from 2011 to 2013, HIV testing increased in TB patients from 58% to 68% and antiretroviral therapy (ART) increased in TB-HIV patients from 54% to 63%. Adverse treatment outcomes in TB-HIV patients increased from 24% to 27%, largely due to transfer out (5–9% increase) and death. The Northern and Highland regions showed poor uptake of TB-HIV interventions. In HCMC, 303 (27%) of 1110 TB-HIV patients had adverse outcomes, with higher risks observed in those with previously treated TB, those diagnosed as HIV-positive before TB onset and those never placed on cotrimoxazole or ART. Conclusion: Despite improving HIV testing rates and TB-HIV interventions, adverse outcomes in TB-HIV patients remain at about 26%. Characteristics predicting higher risk of adverse outcomes must be addressed if Viet Nam wishes to end the TB epidemic by 2030. PMID:27051604

  10. [Financial challenges to access tuberculosis treatment in Ribeirão Preto - São Paulo].

    PubMed

    Arcêncio, Ricardo Alexandre; Arakawa, Tiemi; Oliveira, Mayra Fernanda; Cardozo-Gonzales, Roxana Isabel; Scatena, Lucia Marina; Ruffino-Netto, Antônio; Villa, Tereza Cristina Scatena

    2011-10-01

    The objective of this study was to analyze the financial challenges that patients have to deal with to access the Tuberculosis (TB) Care Reference Centers in Ribeirão Preto. Adjustments were made to the Primary Care Assessment (PCAT) and an opinion poll was made with one-hundred patients following treatment and 16 health care professionals working at TB Reference Centers in Ribeirão Preto. Anova, Kruskall Wallis and chi-square tests were used. Most patients were males and most health care professionals were female. Differences were found between Centers C and A, in that Center C (p=0.028) offers a bus pass, and in A (p=0.010) patients paid for their own transportation. The indicator medical appointment in 24 hours showed a satisfactory level. There were disagreements between the reports from patients and health professionals as to the center offering the bus pass. Patients face challenges in their treatment, such as costs with transportation or being late for work, which result in losses in the family income. PMID:22031372

  11. Impact of Diabetes Mellitus on Treatment Outcomes of Patients with Active Tuberculosis

    PubMed Central

    Dooley, Kelly E.; Tang, Tania; Golub, Jonathan E.; Dorman, Susan E.; Cronin, Wendy

    2009-01-01

    Diabetes mellitus (DM) is an emerging chronic health condition of developed and developing countries. We conducted a retrospective cohort study of patients with active, culture-confirmed tuberculosis (TB) in Maryland to determine the impact of DM on TB treatment outcomes. Of 297 TB patients, 42 (14%) had DM. Patients with diabetes had 2.0 times higher odds of death than patients without diabetes (95% confidence interval [CI] 0.74–5.2, P = 0.18). Adjusting for human immunodeficiency virus (HIV), age, weight, and foreign birth, the odds of death were 6.5 times higher in patients with diabetes than patients without diabetes (95% CI 1.1–38.0, P = 0.039). In pulmonary TB patients, time to sputum culture conversion was longer in patients with diabetes than patients without diabetes (median 49 versus 39 days, P = 0.09). Two-month culture conversion proportions were similar (70% and 69%). Treatment failure occurred in 4.1% of patients without diabetes and 6.7% of patients with diabetes (P = 0.51). In conclusion, DM was a risk factor for death in Maryland TB patients. There was a trend toward increased time to culture conversion; two-month culture conversion proportions, however, were similar. PMID:19346391

  12. Ethnomedical Knowledge of Plants Used for the Treatment of Tuberculosis in Johor, Malaysia

    PubMed Central

    Sabran, Siti Fatimah; Mohamed, Maryati; Abu Bakar, Mohd Fadzelly

    2016-01-01

    This study documented ethnomedical knowledge of plants used for the treatment of tuberculosis (TB) and its related symptoms as practiced by the Jakun community of Kampung Peta, situated in Endau Rompin Johor National Park, Johor, Malaysia. Eight key informants were selected by snowball sampling technique and data about medicinal plants were collected by semistructured interviews, participatory observations, and focus group. Qualitative analysis was undertaken using thematic analysis. There were 23 species of plants (22 genera, 20 families) documented and herbarium specimens were deposited at the UTHM Herbarium. Dipterocarpus sublamellatus was recorded for the first time with ethnomedical uses while other species were previously reported. The qualitative approach employed in this study demonstrates the emic perspective in terms of perceptions on traditional herbal medicine, transfer of knowledge, significant taboos related with medicinal plants, and their conservation efforts. Local and biomedical terminology in treatment of TB showed substantial correspondence. The outcomes obtained in the study are worth being further investigated for conservation strategies and are worthy of verifying their ethnomedical claims scientifically. PMID:26881002

  13. Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011

    PubMed Central

    Tran, Huong Thi Giang; Bui, Quyen Thi Tu

    2016-01-01

    Introduction Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Methods Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. Results A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. Conclusion This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance. PMID:27508089

  14. Elucidating Emergence and Transmission of Multidrug-Resistant Tuberculosis in Treatment Experienced Patients by Whole Genome Sequencing

    PubMed Central

    Clark, Taane G.; Mallard, Kim; Coll, Francesc; Preston, Mark; Assefa, Samuel; Harris, David; Ogwang, Sam; Mumbowa, Francis; Kirenga, Bruce; O’Sullivan, Denise M.; Okwera, Alphonse; Eisenach, Kathleen D.; Joloba, Moses; Bentley, Stephen D.; Ellner, Jerrold J.; Parkhill, Julian; Jones-López, Edward C.; McNerney, Ruth

    2013-01-01

    Background Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings. We have used whole genome analysis to investigate M. tuberculosis strains isolated from treatment experienced patients with MDR-TB in Uganda over a period of four years. Methods and Findings We used high throughput genome sequencing technology to investigate small polymorphisms and large deletions in 51 Mycobacterium tuberculosis samples from 41 treatment-experienced TB patients attending a TB referral and treatment clinic in Kampala. This was a convenience sample representing 69% of MDR-TB cases identified over the four year period. Low polymorphism was observed in longitudinal samples from individual patients (2-15 SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three clusters comprising a total of 8 patients were found with almost identical genetic profiles, including mutations predictive for resistance to rifampicin and isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug susceptible disease were found to have acquired MDR strains, one of which shared its genotype with an isolate from another patient in the cohort. Conclusions Whole genome sequence analysis identified MDR-TB strains that were shared by more than one patient. The transmission of multidrug-resistant disease in this cohort of retreatment patients emphasises the importance of early detection and need for infection control. Consideration should be given to rapid testing for drug resistance in patients undergoing treatment to monitor the

  15. TB-SA antibody test for diagnosis and monitoring treatment outcome of sputum smear negative pulmonary tuberculosis patients.

    PubMed

    Li, Xinxu; Xu, Hancheng; Jiang, Shiwen; Jing, Kuanhe; Wang, Li; Liu, Xiaoqiu; Li, Weibin; Zhang, Hui; Wang, Lixia

    2011-09-01

    The objectives of this study were to evaluate the suitability of the TB-SA antibody test to diagnose tuberculosis in sputum smear negative (SS-) pulmonary tuberculosis (TB) patients and its applicability for monitoring treatment outcomes in these patients. This study was conducted in three counties/districts in Chongqing Municipality, Liaoning Province, China between June 2005 and June 2007. A total of 432 SS suspected pulmonary TB patients were recruited and their blood was collected prior to treatment, at the end of 1 month of treatment, 2 months of treatment and 6 months of treatment (E6MT). The serum samples were analyzed with a TB-SA antibody test kit. Of the 432 SS suspected pulmonary TB patients, serum samples were obtained at all time points in 316 patients and analyzed. The 316 patients were divided into three groups according to sputum smear and sputum culture results and the chest X-ray results before treatment and at E6MT. Ten point four percent were SS-/culture positive (C+), 73.1% were SS-/culture negative (C-) with X-rays abnormalities, and 16.5% were SS-/C- without X-rays abnormalities. The positive rates for TB-SA antibody in the three groups were 57.6, 44.6 and 44.2%, respectively, before treatment, and 18.2, 19.1 and 26.9%, respectively, at E6MT. There was a significant decrease in TB-SA antibody positivity with treatment for all 3 groups. The TB-SA antibody test may be a useful adjunct to diagnose tuberculosis in SS- pulmonary TB patients, and may be useful for monitoring treatment outcomes of SS- pulmonary TB patients. PMID:22299440

  16. Pharmacokinetic Evaluation of Sulfamethoxazole at 800 Milligrams Once Daily in the Treatment of Tuberculosis.

    PubMed

    Alsaad, N; Dijkstra, J A; Akkerman, O W; de Lange, W C M; van Soolingen, D; Kosterink, J G W; van der Werf, T S; Alffenaar, J W C

    2016-07-01

    For treatment of multidrug-resistant tuberculosis (MDR-TB), there is a scarcity of antituberculosis drugs. Co-trimoxazole is one of the available drug candidates, and it is already frequently coprescribed for TB-HIV-coinfected patients. However, only limited data are available on the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of co-trimoxazole in TB patients. The objective of this study was to evaluate the PK parameters and in vitro PD data on the effective part of co-trimoxazole: sulfamethoxazole. In a prospective PK study in patients infected with drug-susceptible Mycobacterium tuberculosis (drug-susceptible TB patients) (age, >18), sulfamethoxazole-trimethoprim (SXT) was administered orally at a dose of 960 mg once daily. One-compartment population pharmacokinetic modeling was performed using MW\\Pharm 3.81 (Mediware, Groningen, The Netherlands). The area under the concentration-time curve for the free, unbound fraction of a drug (ƒAUC)/MIC ratio and the period in which the free concentration exceeded the MIC (fT > MIC) were calculated. Twelve patients received 960 mg co-trimoxazole in addition to first-line drugs. The pharmacokinetic parameters of the population model were as follows (geometric mean ± standard deviation [SD]): metabolic clearance (CLm), 1.57 ± 3.71 liters/h; volume of distribution (V), 0.30 ± 0.05 liters · kg lean body mass(-1); drug clearance/creatinine clearance ratio (fr), 0.02 ± 0.13; gamma distribution rate constant (ktr_po), 2.18 ± 1.14; gamma distribution shape factor (n_po), 2.15 ± 0.39. The free fraction of sulfamethoxazole was 0.3, but ranged between 0.2 and 0.4. The median value of the MICs was 9.5 mg/liter (interquartile range [IQR], 4.75 to 9.5), and that of theƒAUC/MIC ratio was 14.3 (IQR, 13.0 to 17.5). The percentage of ƒT > MIC ranged between 43 and 100% of the dosing interval. The PK and PD data from this study are useful to explore a future dosing regimen of co-trimoxazole for MDR-TB treatment. (This

  17. Endobronchial Tuberculosis Mimicking Asthma

    PubMed Central

    Argun Baris, Serap; Onyilmaz, Tuğba; Basyigit, Ilknur; Boyaci, Hasim

    2015-01-01

    Endobronchial tuberculosis (EBTB) is defined as tuberculosis infection of the tracheobronchial tree with microbial and histopathological evidence. The clinical symptoms of the diseases are nonspecific. Chronic cough is the major symptom of the disease. The diagnosis is often delayed due to its nonspecific presentation and misdiagnosed as bronchial asthma. This case is presented to recall the notion that the endobronchial tuberculosis can mimic asthma and the importance of bronchoscopic evaluation in a patient with chronic cough and treatment resistant asthma. PMID:26798513

  18. Predictors of Death among Patients Who Completed Tuberculosis Treatment: A Population-Based Cohort Study

    PubMed Central

    Millet, Juan-Pablo; Orcau, Angels; Rius, Cristina; Casals, Marti; de Olalla, Patricia Garcia; Moreno, Antonio; Nelson, Jeanne L.; Caylà, Joan A.

    2011-01-01

    Background Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. Methods A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995–1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 41–60 years old (HR: 3.5; CI:2.1–5.7), age greater than 60 years (HR: 14.6; CI:8.9–24), alcohol abuse (HR: 1.7; CI:1.2–2.4) and HIV-infected IDU (HR: 7.9; CI:4.7–13.3). Conclusions The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival. PMID:21980423

  19. Cost-comparison of different management policies for tuberculosis patients in Italy. AIPO TB Study Group.

    PubMed Central

    Migliori, G. B.; Ambrosetti, M.; Besozzi, G.; Farris, B.; Nutini, S.; Saini, L.; Casali, L.; Nardini, S.; Bugiani, M.; Neri, M.; Raviglione, M. C.

    1999-01-01

    Although in developing countries the treatment of tuberculosis (TB) cases is among the most cost-effective health interventions, few studies have evaluated the cost-effectiveness of TB control in low-prevalence countries. The aim of the present study was to carry out an economic analysis in Italy that takes into account both the perspective of the resource-allocating authority (i.e. the Ministry of Health) and the broader social perspective, including a cost description based on current outcomes applied to a representative sample of TB patients nationwide (admission and directly observed treatment (DOT) during the initial intensive phase of treatment); a cost-comparison analysis of two alternative programmes: current policy based on available data (scenario 1) and an hypothetical policy oriented more towards outpatient care (scenario 2) (both scenarios included the option of including or not including DOT outside hospital admission, and incentives) were compared in terms of cost per case treated successfully. Indirect costs (such as loss of productivity) were included in considerations of the broader social perspective. The study was designed as a prospective monitoring activity based on the supervised collection of forms from a representative sample of Italian TB units. Individual data were collected and analysed to obtain a complete economic profile of the patients enrolled and to evaluate the effectiveness of the intervention. A separate analysis was done for each scenario to determine the end-point at different levels of cure rate (50-90%). The mean length of treatment was 6.6 months (i.e. patients hospitalized during the intensive phase; length of stay was significantly higher in smear-positive patients and in human immunodeficiency virus (HIV) seropositive patients). Roughly six direct smear and culture examinations were performed during hospital admission and three during ambulatory treatment. The cost of a single bed day was US$186.90, whereas that of a

  20. Accessibility to tuberculosis control services and tuberculosis programme performance in southern Ethiopia

    PubMed Central

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

    2015-01-01

    Background Despite the expansion of health services and community-based interventions in Ethiopia, limited evidence exists about the distribution of and access to health facilities and their relationship with the performance of tuberculosis (TB) control programmes. We aim to assess the geographical distribution of and physical accessibility to TB control services and their relationship with TB case notification rates (CNRs) and treatment outcome in the Sidama Zone, southern Ethiopia. Design We carried out an ecological study to assess physical accessibility to TB control facilities and the association of physical accessibility with TB CNRs and treatment outcome. We collected smear-positive pulmonary TB (PTB) cases treated during 2003–2012 from unit TB registers and TB service data such as availability of basic supplies for TB control and geographic locations of health services. We used ArcGIS 10.2 to measure the distance from each enumeration location to the nearest TB control facilities. A linear regression analysis was employed to assess factors associated with TB CNRs and treatment outcome. Results Over a decade the health service coverage (the health facility–to-population ratio) increased by 36% and the accessibility to TB control facilities also improved. Thus, the mean distance from TB control services was 7.6 km in 2003 (ranging from 1.8 to 25.5 km) between kebeles (the smallest administrative units) and had decreased to 3.2 km in 2012 (ranging from 1.5 to 12.4 km). In multivariate linear regression, as distance from TB diagnostic facilities (b-estimate=−0.25, p<0.001) and altitude (b-estimate=−0.31, p<0.001) increased, the CNRs of TB decreased, whereas a higher population density was associated with increased TB CNRs. Similarly, distance to TB control facilities (b-estimate=−0.27, p<0.001) and altitude (b-estimate=−0.30, p<0.001) were inversely associated with treatment success (proportion of treatment completed or cured cases). Conclusions

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

    PubMed Central

    Sharma, Surendra K.; Mohan, Alladi; Chauhan, L.S.; Narain, J.P.; Kumar, P.; Behera, D.; Sachdeva, K.S.; Kumar, Ashok

    2013-01-01

    Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of ‘new smear-positives’ diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement. PMID:23563371

  2. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis.

    PubMed Central

    Tramontana, J. M.; Utaipat, U.; Molloy, A.; Akarasewi, P.; Burroughs, M.; Makonkawkeyoon, S.; Johnson, B.; Klausner, J. D.; Rom, W.; Kaplan, G.

    1995-01-01

    BACKGROUND: The monocyte-derived cytokine, tumor necrosis factor alpha (TNF alpha), is essential for host immunity, but overproduction of this cytokine may have serious pathologic consequences. Excess TNF alpha produced in pulmonary tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive weight loss. Thalidomide (alpha-N-phthalimidoglutarimide) has recently been shown to suppress TNF alpha production by human monocytes in vitro and to reduce serum TNF alpha in leprosy patients. We have therefore conducted a two-part placebo-controlled pilot study of thalidomide in patients with active tuberculosis to determine its effects on clinical response, immune reactivity, TNF alpha levels, and weight. MATERIALS AND METHODS: 30 male patients with active tuberculosis, either human immunodeficiency virus type 1 positive (HIV-1+) or HIV-1-, received thalidomide or placebo for single or multiple 14 day cycles. Toxicity of the study drug, delayed type hypersensitivity (DTH), cytokine production, and weight gain were evaluated. RESULTS: Thalidomide treatment was well tolerated, without serious adverse events. The drug did not adversely affect the DTH response to purified protein derivative (PPD), total leukocyte, or differential cell counts. TNF alpha production was significantly reduced during thalidomide treatment while interferon-gamma (IFN gamma) production was enhanced. Daily administration of thalidomide resulted in a significant enhancement of weight gain. CONCLUSIONS: The results indicate that thalidomide is well tolerated by patients receiving anti-tuberculosis therapy. Thalidomide treatment reduces TNF alpha production both in vivo and in vitro and is associated with an accelerated weight gain during the study period. PMID:8521296

  3. Prevention of hepatotoxicity due to anti tuberculosis treatment: A novel integrative approach

    PubMed Central

    Adhvaryu, Meghna R; Reddy, Narsimha M; Vakharia, Bhasker C

    2008-01-01

    AIM: To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity. METHODS: Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result. RESULTS: Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316, P < 0.0001). Mean aspartate transaminase (AST) (195.93 ± 108.74 vs 85 ± 4.24, P < 0.0001), alanine transaminase (ALT) (75.74 ± 26.54 vs 41 ± 1.41, P < 0.0001) and serum bilirubin (5.4 ± 3.38 vs 1.5 ± 0.42, P < 0.0001). A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P = 0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278, P = 0.0037) was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P < 0.0001). CONCLUSION: The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects. PMID:18720535

  4. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis.

    PubMed

    Pym, Alexander S; Diacon, Andreas H; Tang, Shen-Jie; Conradie, Francesca; Danilovits, Manfred; Chuchottaworn, Charoen; Vasilyeva, Irina; Andries, Koen; Bakare, Nyasha; De Marez, Tine; Haxaire-Theeuwes, Myriam; Lounis, Nacer; Meyvisch, Paul; Van Baelen, Ben; van Heeswijk, Rolf P G; Dannemann, Brian

    2016-02-01

    Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline.Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline.Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively.Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB. PMID:26647431

  5. Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response

    PubMed Central

    Nam, Sung-Jin; Jeong, Jee-Yeong; Jang, Tae-Won; Jung, Mann-Hong; Chun, Bong-Kwon; Cha, Hee-Jae; Oak, Chul-Ho

    2016-01-01

    Background/Aims: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. Methods: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. Results: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. Conclusions: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions. PMID:27271274

  6. New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid

    PubMed Central

    Brigden, Grania; Hewison, Cathy; Varaine, Francis

    2015-01-01

    The current treatment for drug-resistant tuberculosis (TB) is long, complex, and associated with severe and life-threatening side effects and poor outcomes. For the first time in nearly 50 years, there have been two new drugs registered for use in multidrug-resistant TB (MDR-TB). Bedaquiline, a diarylquinoline, and delamanid, a nitromidoxazole, have received conditional stringent regulatory approval and have World Health Organization interim policy guidance for their use. As countries improve and scale up their diagnostic services, increasing number of patients with MDR-TB and extensively drug-resistant TB are identified. These two new drugs offer a real opportunity to improve the outcomes of these patients. This article reviews the evidence for these two new drugs and discusses the clinical questions raised as they are used outside clinical trial settings. It also reviews the importance of the accompanying drugs used with these new drugs. It is important that barriers hindering the use of these two new drugs are addressed and that the existing clinical experience in using these drugs is shared, such that their routine-use programmatic conditions is scaled up, ensuring maximum benefit for patients and countries battling the MDR-TB crisis. PMID:26586956

  7. Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis

    PubMed Central

    Tupasi, Thelma; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

    2016-01-01

    Abstract Problem New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. Approach We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization – Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Local setting Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Relevant changes Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Lessons learnt Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial. PMID:26908964

  8. Universal public finance of tuberculosis treatment in India: an extended cost-effectiveness analysis.

    PubMed

    Verguet, Stéphane; Laxminarayan, Ramanan; Jamison, Dean T

    2015-03-01

    Universal public finance (UPF)-government financing of an intervention irrespective of who is receiving it-for a health intervention entails consequences in multiple domains. First, UPF increases intervention uptake and hence the extent of consequent health gains. Second, UPF generates financial consequences including the crowding out of private expenditures. Finally, UPF provides insurance either by covering catastrophic expenditures, which would otherwise throw households into poverty or by preventing diseases that cause them. This paper develops a method-extended cost-effectiveness analysis (ECEA)-for evaluating the consequences of UPF in each of these domains. It then illustrates ECEA with an evaluation of UPF for tuberculosis treatment in India. Using plausible values for key parameters, our base case ECEA concludes that the health gains and insurance value of UPF would accrue primarily to the poor. Reductions in out-of-pocket expenditures are more uniformly distributed across income quintiles. A variant on our base case suggests that lowering costs of borrowing for the poor could potentially achieve some of the health gains of UPF, but at the cost of leaving the poor more deeply in debt. PMID:24497185

  9. Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.

    PubMed

    Tientcheu, L D; Maertzdorf, J; Weiner, J; Adetifa, I M; Mollenkopf, H-J; Sutherland, J S; Donkor, S; Kampmann, B; Kaufmann, S H E; Dockrell, H M; Ota, M O

    2015-01-01

    The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages. PMID:26043170

  10. [Guidelines for the diagnosis and treatment of latent tuberculosis infection and active tuberculosis in patients with inflammatory joint diseases proposed for treatment with tumour necrosis factor alpha antagonist drugs].

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2006-01-01

    The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-a) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-a therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-a therapy. If the IJD activity requires urgent anti-TNF-a therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-a therapy, even in the presence of a negative test. PMID:17117328

  11. Anterolateral radical debridement and interbody bone grafting combined with transpedicle fixation in the treatment of thoracolumbar spinal tuberculosis.

    PubMed

    Cheng, Zhaohui; Wang, Jian; Zheng, Qixin; Wu, Yongchao; Guo, Xiaodong

    2015-04-01

    This retrospective cohort study was conducted to evaluate the clinical outcomes of radical anterolateral debridement and autogenous ilium with rib or titanium cage interbody autografting with transpedicle fixation for the treatment of thoracolumbar tuberculosis. Spinal tuberculosis operation aims to remove the lesions and necrotic tissues, remove spinal cord compression, and reconstruct spinal stability. However, traditional operation methods cannot effectively correct cyrtosis or stabilize the spine. In addition, the patient needs to stay in bed for a long time and may have many complications. So far, the best surgical method and fixation method for spinal tuberculosis remain controversial. There were a total of 43 patients, 16 involving spinal cord injury, from January 2004 to January 2011. The patients were surgically treated for radical anterolateral debridement via posterolateral incision and autogenous ilium with rib or titanium cage interbody autografting and single-stage transpedicle fixation. All the patients were followed up to determine the stages of intervertebral bone fusion and the corrections of spinal kyphosis with the restoration of neurological deficit. The erythrocyte sedimentation rate (ESR) of these patients decreased to normal levels for a mean of 2.8 months. The function of feeling, motion, and sphincter in 16 paraplegia cases gradually recovered after 1 week to 3 months postoperatively, and the American Spinal Injury Association scores significantly increased at the final follow-up. Intervertebral bone fusions were all achieved postoperatively. No internal fixation devices were loose, extracted, or broken. There was no correction degree loss during the follow-up. The method of radical anterolateral debridement and autogenous ilium with rib or titanium cage interbody autografting and single-stage transpedicle fixation was effective for the treatment of thoracolumbar tuberculosis, correcting kyphotic deformity, and reconstructing spinal

  12. Safety and effectiveness of CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy for the treatment of pleural tuberculosis

    PubMed Central

    Geng, Shujun; Li, Lijuan; Liu, Jianling; Song, Tao

    2016-01-01

    The aim of the study was to compare the mid- and long-term effects of different treatments such as CT-guided percutaneous pulmonary paracentesis, tuberculoma perfusing chemotherapy and whole-body standard chemotherapy or extended chemotherapy on safety and effectiveness for pleural chemotherapy. A total of 60 subjects diagnosed to have pleural tuberculosis between February 2010 and February 2014 were prospectively selected for this study and were considered as the experimental group. Seventy pleural tuberculosis patients who underwent treatment between February 2006 and February 2010 were considered as the control group. The patients in the experimental group were treated with CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy of not more than three courses with each course consisting of administration of 0.1 g isoniazid, n 0.5 gkanamyci, 0.2 g levofloxacin, and 1 ml lidocaine once a week for four times. The patients in the control group were treated with whole-body standard or extended chemotherapy regimen 3~6HRZE(S)/6~12HR. The patients were followed up for 18 months and the treatment effects were compared. The diameter of tuberculoma in patients of the experimental group during 6, 12 and 18 months was shorter than that of the control group (P<0.05). The total effective rate of treatment and the duration of treatment in experimental group during 18 months were higher than that of control group (P<0.05). The frequency of drug-related complications were lower in comparison with the control group (P<0.05). No surgically acquired complications were observed in the experimental group. Thus, treatments such as CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy for pleural tuberculosis are safe and effective, which has greater value and can be promoted for use in the clinical setting. PMID:27446302

  13. Integrated Pre-Antiretroviral Therapy Screening and Treatment for Tuberculosis and Cryptococcal Antigenemia

    PubMed Central

    Pac, Lincoln; Horwitz, Mara; Namutebi, Anne Marion; Auerbach, Brandon J.; Semeere, Aggrey; Namulema, Teddy; Schwarz, Miriam; Bbosa, Robert; Muruta, Allan; Meya, David; Manabe, Yukari C.

    2015-01-01

    Objective To demonstrate the feasibility of integrated screening for cryptococcal antigenemia and tuberculosis (TB) prior to antiretroviral therapy (ART) initiation and to assess disease specific and all-cause mortality in the first 6 months of follow-up. Methods We enrolled a cohort of HIV-infected, ART-naïve adults with CD4 counts ≤ 250 cells/µL in rural Uganda who were followed for 6 months after ART initiation. All subjects underwent screening for TB; those with CD4 ≤ 100 cells/µL also had cryptococcal antigen (CrAg) screening. For those who screened positive, standard treatment for TB or preemptive treatment for cryptococcal infection was initiated, followed by ART two weeks later. Results Of 540 participants enrolled, pre-ART screening detected 10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count ≤ 100 cells/µL) with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed with TB and one patient developed cryptococcal meningitis. Overall 7.2% of participants died (incidence rate 15.6 per 100 person years at risk). Death rates were significantly higher among subjects with TB and cryptococcal antigenemia compared to subjects without these diagnoses. In multivariate analysis, significant risk factors for mortality were male sex, baseline anemia of hemoglobin ≤ 10 mg/dL, wasting defined as body mass index ≤ 15.5 kg/m2, and opportunistic infections (TB, positive serum CrAg). Conclusion Pre-ART screening for opportunistic infections detects many prevalent cases of TB and cryptococcal infection. However, severely immunosuppressed and symptomatic HIV patients continue to experience high mortality after ART initiation. PMID:25761234

  14. Pulmonary Paragonimiasis Mimicking Tuberculosis.

    PubMed

    Prasad, Kj; Basu, Arup; Khana, Shilpi; Wattal, Chand

    2015-08-01

    Paragonimiasis is a disease which is frequently misdiagnosed as pulmonary tuberculosis. In the areas where people eat crab/crayfish this disease should be considered in the differential diagnosis to avoid antituberculosis treatment for a non-tubercular condition. We are reporting a case of pulmonary paragonimiasis who had been treated for tuberculosis. PMID:27604443

  15. Completion Rate and Side-Effect Profile of Three-Month Isoniazid and Rifapentine Treatment for Latent Tuberculosis Infection in an Urban County Jail

    PubMed Central

    Juarez-Reyes, Maria; Gallivan, Mark; Chyorny, Alexander; O'Keeffe, Linda; Shah, Neha S.

    2016-01-01

    In an urban jail population, 3 months of isoniazid and rifapentine (3HP) was associated with an 85% latent tuberculosis infection treatment completion rate compared with 18% in a standard 9-month isoniazid treatment group. Among the 91 patients who started 3HP therapy, there were 2 treatment discontinuations from adverse drug reactions. PMID:26885547

  16. Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

    PubMed Central

    Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B.B.; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

    2014-01-01

    Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing

  17. Association Between Staff Experience and Effective Tuberculosis Contact Tracing in North Carolina, 2008–2009

    PubMed Central

    Bryant, Kia. E.; Allen, Myra G.; Fortenberry, Ellen R.; Luffman, Julie; Zeringue, Elizabeth; Stout, Jason E.

    2016-01-01

    BACKGROUND Effective investigation of tuberculosis (TB) contacts is essential for continued progress toward TB elimination. As the incidence of TB declines, staff experience will also decline. Little is known about the association between the experience level of public health TB staff and the quality of contact investigations. METHODS Contact investigations involving fewer than 30 contacts during the period 2008–2009 were included in this analysis. Multivariable models were used to examine associations between staff TB experience (assessed by a standardized survey) and measures of contact investigation quality: time from case identification to contact identification and number of contacts identified per case investigated. RESULTS A total of 501 cases and 3,230 contacts met the inclusion criteria. Data were stratified by the number of cases in the county and whether the case was smear-positive or smear-negative. For contacts of smear-positive cases, greater staff experience was associated with more rapid contact identification both in counties with high case counts (hazard ratio [HR] = 2.43; 95% CI, 1.79–3.31) and in counties with low case counts (HR = 1.142; 95% CI, 0.95–1.37). However, for smear-negative cases, staff in counties with low case counts identified contacts more slowly as years of experience increased (HR = 0.82; 95% CI, 0.62–1.07). For contacts of smear-negative cases, more contacts (relative risk [RR] = 1.20; 95% CI, 1.07–1.35) were identified per case in high case-count counties (more than 20 cases during 2008–2009). Conversely, in low case-count counties, fewer contacts were identified per case (RR = 0.94; 95% CI, 0.82–1.08); however, this finding was not significant. DISCUSSION Speed of identification and number of contacts are imperfect surrogates for the most important outcome of contact investigations—that is, the rapid identification and treatment of infected contacts. CONCLUSION More TB experience was associated with more

  18. Characterization and evaluation of the directly observed treatment for tuberculosis in Santiago de Compostela (1996–2006)

    PubMed Central

    Mejuto, Beatriz; Tuñez, Victoria; del Molino, María Luisa Pérez; García, Rosario

    2010-01-01

    Objective To realize a retrospective study of the characterization, results, and effectiveness of directly observed therapy, short course (DOTS) in the regional health area of Santiago de Compostela (population 453 068) between 1996 and 2006. Design Tuberculosis (TB) patient cases involved in DOTS treatment were reviewed. The studied variables included: age, sex, type of TB, TB location, microbiological studies, chest radiology, pattern and treatment duration, final status of case, and TB recurrence. Results There were 2456 diagnosed TB cases in the time period studied and 259 received DOTS. The reasons for inclusion in this treatment strategy were social dystocia in 33.2% of cases, retreatment in 30.8% of cases, alcoholism in 29.3% of cases, drug use in 17.4% of cases, HIV coinfection in 11.6% of cases, multidrug-resistant strains of TB (MDR-TB) in 3.1%, and being an immigrant in 1.9% of cases. Primary TB represented 3.5% of the instances and pulmonary TB represented 87.6%. Bacteriological confirmation was performed in 76.8% of this population. Cavitated forms in chest radiology were shown in 46.7% of patients. Standard treatment guidelines were used in 71.4% of patients. Treatment adherence was achieved in 96.1% of the cases and 86.9% cases had a successful final status. Recurrence of TB was 1.5%. Conclusion Although it is not possible to determine the exact influence of the DOTS strategy, its introduction under the conditions of the Galician Program for Prevention and Control of Tuberculosis (GPPCT)5 has worked to improve the control of tuberculosis in our health area. PMID:22312214

  19. Month 2 Culture Status and Treatment Duration as Predictors of Recurrence in Pulmonary Tuberculosis: Model Validation and Update

    PubMed Central

    Wallis, Robert S.; Peppard, Thomas; Hermann, David

    2015-01-01

    Background New regimens capable of shortening tuberculosis treatment without increasing the risk of recurrence are urgently needed. A 2013 meta-regression analysis, using data from trials published from 1973 to 1997 involving 7793 patients, identified 2-month sputum culture status and treatment duration as independent predictors of recurrence. The resulting model predicted that if a new 4-month regimen reduced the proportion of patients positive at month 2 to 1%, it would reduce to 10% the risk of a relapse rate >10% in a trial with 680 subjects per arm. The 1% target was far lower than anticipated. Methods Data from the 8 arms of 3 recent unsuccessful phase 3 treatment-shortening trials of fluoroquinolone-substituted regimens (REMox, OFLOTUB, and RIFAQUIN) were used to assess and refine the accuracy of the 2013 meta-regression model. The updated model was then tested using data from a treatment shortening trial reported in 2009 by Johnson et al. Findings The proportions of patients with recurrence as predicted by the 2013 model were highly correlated with observed proportions as reported in the literature (R2 = 0.86). Using the previously proposed threshold of 10% recurrences as the maximum likely considered acceptable by tuberculosis control programs, the original model correctly identified all 4 six-month regimens as satisfactory, and 3 of 4 four-month regimens as unsatisfactory (sensitivity = 100%, specificity = 75%, PPV = 80%, and NPV = 100%). A revision of the regression model based on the full dataset of 66 regimens and 11181 patients resulted in only minimal changes to its predictions. A test of the revised model using data from the treatment shortening trial of Johnson et al found the reported relapse rates in both arms to be consistent with predictions. Interpretation Meta-regression modeling of recurrence based on month 2 culture status and regimen duration can inform the design of future phase 3 tuberculosis clinical trials. PMID:25923700

  20. Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research

    PubMed Central

    Kim, Hye Won; Kwon, Seong Ryul; Jung, Kyong-Hee; Kim, Seong-Kyu; Baek, Han Joo; Seo, Mi Ryung; Bang, So-Young; Lee, Hye-Soon; Suh, Chang-Hee; Jung, Ju Yang; Son, Chang-Nam; Shim, Seung Cheol; Lee, Sang-Hoon; Lee, Seung-Geun; Lee, Yeon-Ah; Lee, Eun Young; Kim, Tae-Hwan

    2016-01-01

    Backgrounds Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors. Methods Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually. Findings Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8–66.7] months). Conclusions Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early

  1. Surveillance data analysis of Revised National Tuberculosis Control Program of Kangra, Himachal Pradesh

    PubMed Central

    Gupta, Surender Nikhil; Gupta, Naveen; Gupta, Shivani

    2013-01-01

    Background: The annual risk of tuberculosis infection is 1.9% in Himachal Pradesh against a national average of 1%. Revised national tuberculosis control program (RNTCP) in Kangra was introduced in October, 1998. We analyzed the 5-year (2001-2005) RNTCP secondary data from Kangra to evaluate the performance of the program. Materials and Methods: We collected data from all the five tuberculosis units the district. We calculated the following indicators-case detection rate, tuberculosis cases by category-new smear positive (or smear negative but seriously ill) defaulters, relapses and failures, extra-pulmonary, and new smear negative cases. We compared the results with Himachal Pradesh and India. We employed the standardized program indicators-sputum positivity, cure, death, failure and default rates. Results: Extra pulmonary cases ranged in between 56% and 73%, normal being 15-20%. The highest category-1 varies from 42% to 48%. New smear positive case detection rates (78-90%) and cure rates (88-91%) were the highest as compared to figures of the state and country. Failure rate was maximum in Kangra Tuberculosis Units (TU)-6.5% and the default rate was 7.2% in TU Palampur. The tuberculosis cases have fallen down from 6,462/100, 000 in 1999 to 2,195/100, 000 in 2005 following the introduction of RNTCP in 1999. Age specific (15-55 years) and sex-wise males were more affected than the females (59-64%). Conclusions: Continue investment in the program to sustain progress achieved. Investigate the cause of high proportion of extra-pulmonary tuberculosis. Investigate Kangra TU unit with a high default rate. PMID:24479092

  2. Risk of developing tuberculosis after brief exposure in Norwegian children: results of a contact investigation

    PubMed Central

    Døllner, Henrik; Ramm, Christina Terez; Harstad, Ingunn; Afset, Jan Egil; Sagvik, Eli

    2012-01-01

    Objective Prolonged exposure to adults with pulmonary tuberculosis is a risk factor for infecting children. We have studied to what extent a brief exposure may increase the risk of being infected in children. Design Observational study of a tuberculosis contact investigation. Setting 7 day-care centres and 4 after-school-care centres in Norway. Participants 606 1-year-old to 9-year-old children who were exposed briefly to a male Norwegian with smear-positive pulmonary tuberculosis. Main outcome measures Number of children with latent and active tuberculosis detected by routine clinical examination, chest x-ray and use of a Mantoux tuberculin skin test (TST) and an interferon-γ release assay (IGRA). Results The children were exposed to a mean of 6.9 h (range 3–18 h). 2–3 months after the exposure, 11 children (1.8%) had a TST ≥6 mm, 6 (1.0%) had TST 4–5 mm, and 587 (97.2%) had a negative TST result. Two children (0.3%) with negative chest x-rays who were exposed 4.75 and 12 h, respectively, had a positive IGRA test result, and were diagnosed with latent tuberculosis. None developed active tuberculosis. Conclusions Children from a high-income country attending day-care and after-school-care centres had low risk of being infected after brief exposure less than 18 h to an adult day-care helper with smear-positive pulmonary tuberculosis. PMID:23135543

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

    PubMed Central

    2013-01-01

    Background In 2010, there were approximately 8.8 million incident cases of tuberculosis (TB) worldwide. The treatment of TB is at least six months long and may be complicated by a high pill burden. In addition, TB patients often do not take their medication on schedule simply because they forget. Mobile phone text messaging has the potential to help promote TB treatment adherence. We, therefore, propose to conduct a review of current best evidence for the use of mobile phone text messaging to promote patient adherence to TB treatment. Methods This is a systematic review of the literature. We will preferably include randomized controlled trials (RCTs). However, non-randomized studies (NRS) will be considered if there is an inadequate number of RCTs. We will search PubMed, EMBASE, CINAHL, CENTRAL, Science Citation Index, Africa-Wide Information, and WHOLIS electronic databases for eligible studies available by 30 November 2012 regardless of language or publication status. We will also check reference lists for additional studies, identify abstracts from conference proceedings and communicate with authors for any relevant material. At least two authors will independently screen search outputs, select studies, extract data and assess the risk of bias (using separate criteria for RCTs and NRS); resolving discrepancies by discussion and consensus. We will assess clinical heterogeneity by examining the types of participants, interventions and outcomes in each study and pool studies judged to be clinically homogenous. We will also assess statistical heterogeneity using the chi-square test of homogeneity and quantify it using the I-square statistic. If study results are found to be statistically homogeneous (that is heterogeneity P > 0.1), we will pool them using the fixed-effect meta-analysis. Otherwise, we will use random-effects meta-analysis. We will calculate risk ratios and their corresponding 95% confidence intervals for dichotomous outcomes, and mean differences for

  4. Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment

    PubMed Central

    Liu, Qin; Abba, Katharine; Alejandria, Marissa M; Sinclair, David; Balanag, Vincent M; Lansang, Mary Ann D

    2014-01-01

    Background People with active tuberculosis (TB) require six months of treatment. Some people find it difficult to complete treatment, and there are several approaches to help ensure completion. One such system relies on reminders, where the health system prompts patients to attend for appointments on time, or re-engages people who have missed or defaulted on a scheduled appointment. Objectives To assess the effects of reminder systems on improving attendance at TB diagnosis, prophylaxis, and treatment clinic appointments, and their effects on TB treatment outcomes. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Effective Practice andOrganization of Care Group Specialized Register, CENTRAL,MEDLINE, EMBASE, LILACS, CINAHL, SCI-EXPANDED, SSCI, m RCT, and the Indian Journal of Tuberculosis without language restriction up to 29 August 2014. We also checked reference lists and contacted researchers working in the field. Selection criteria Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing reminder systems with no reminders or an alternative reminder system for people with scheduled appointments for TB diagnosis, prophylaxis, or treatment. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in the included trials. We compared the effects of interventions by using risk ratios (RR) and presented RRs with 95% confidence intervals (CIs). Also we assessed the quality of evidence using the GRADE approach. Main results Nine trials, including 4654 participants, met our inclusion criteria. Five trials evaluated appointment reminders for people on treatment for active TB, two for people on prophylaxis for latent TB, and four for people undergoing TB screening using skin tests.We classified the interventions into 'pre-appointment' reminders (telephone calls or letters prior to a scheduled appointment) or

  5. Evaluation of community-based treatment for drug-resistant tuberculosis in Bangladesh

    PubMed Central

    Cavanaugh, Joseph S.; Kurbatova, Ekaterina; Alami, Negar N.; Mangan, Joan; Sultana, Zinia; Ahmed, Shahriar; Begum, Vikarunessa; Sultana, Sabera; Daru, Paul; Ershova, Julia; Golubkov, Alexander; Banu, Sayera; Heffelfinger, James D.

    2015-01-01

    OBJECTIVE Drug-resistant tuberculosis (TB) threatens global TB control because it is difficult to diagnose and treat. Community-based programmatic management of drug-resistant TB (cPMDT) has made therapy easier for patients, but data on these models are scarce. Bangladesh initiated cPMDT in 2012, and in 2013, we sought to evaluate programme performance. METHODS In this retrospective review, we abstracted demographic, clinical, microbiologic and treatment outcome data for all patients enrolled in the cPMDT programme over 6 months in three districts of Bangladesh. We interviewed a convenience sample of patients about their experience in the programme. RESULTS Chart review was performed on 77 patients. Sputum smears and cultures were performed, on average, once every 1.35 and 1.36 months, respectively. Among 74 initially culture-positive patients, 70 (95%) converted their cultures and 69 (93%) patients converted the cultures before the sixth month. Fifty-two (68%) patients had evidence of screening for adverse events. We found written documentation of musculoskeletal complaints for 16 (21%) patients, gastrointestinal adverse events for 16 (21%), hearing loss for eight (10%) and psychiatric events for four (5%) patients; conversely, on interview of 60 patients, 55 (92%) reported musculoskeletal complaints, 54 (90%) reported nausea, 36 (60%) reported hearing loss, and 36 (60%) reported psychiatric disorders. CONCLUSIONS The cPMDT programme in Bangladesh appears to be programmatically feasible and clinically effective; however, inadequate monitoring of adverse events raises some concern. As the programme is brought to scale nationwide, renewed efforts at monitoring adverse events should be prioritised. PMID:26489698

  6. Successful treatment of multidrug-resistant tuberculosis following drug-induced hepatic necrosis requiring liver transplant.

    PubMed

    Marra, F; Cox, V C; FitzGerald, J M; Moadebi, S; Elwood, R K

    2004-07-01

    A 28-year-old female developed multidrug-resistant (MDR) tuberculous lymphadenitis following a trip to India. She was initially treated with a four-drug regimen of first-line anti-tuberculosis medications, but when sensitivities indicated resistance to isoniazid and rifampin, her regimen was altered to ciprofloxacin (CFX), pyrazinamide (PZA) and ethambutol. She subsequently developed a rash, flu-like symptoms and fever, which progressed to acute hepatic necrosis despite discontinuation of medication. The clinical presentation and subsequent investigations suggested a hypersensitivity reaction, possibly related to the quinolone. The patient subsequently had an orthoptic liver transplant; second-line anti-tuberculosis medications were restarted to which she responded clinically and radiologically. Our findings raise the possibility that the CFX and PZA combination was responsible for the hepatic necrosis. The patient also illustrates that active, even MDR tuberculosis is not a contraindication to hepatic transplant. PMID:15260286

  7. Abandonment of Treatment for Latent Tuberculosis Infection and Socioeconomic Factors in Children and Adolescents: Rio De Janeiro, Brazil

    PubMed Central

    Mendonça, Angela Marcia Cabral; Kritski, Afrânio Lineu; Land, Marcelo Gerardin Poirot; Sant’Anna, Clemax Couto

    2016-01-01

    Background Routine data on the use of isoniazid preventive therapy (IPT) in children and adolescents are scarce in high tuberculosis (TB) burden countries. Objective To describe the factors related to abandonment of IPT in children and adolescents with latent tuberculosis infection (LTBI) receiving routine care. Methods Retrospective (2005–2009) descriptive study of 286 LTBI cases with indication of IPT and serviced at a pediatric hospital in the State of Rio de Janeiro, Brazil. Survival analysis of the risk of abandonment of IPT over six months was performed, including multivariate analysis using the Cox proportional hazards model. Results Out of the 245 cases of LTBI included, 62 abandoned IPT (25.3%; 95% CI: 20%-31%). On multivariate analysis, the variables related to the IPT abandonment hazard ratio were the Human Development Index (HDI) (hazard ratio—HR: 0.004; 0.000–0.569) of the place of residence and the contact with adults that were not undergoing anti-TB treatment (HR: 7.30; 1.00–53.3). Conclusion This study reveals the relevance of the relation of abandonment of IPT to the socioeconomic conditions at the place of residence and poor adherence to the active TB treatment. Educational measures to stimulate preventive treatment of child contacts and curative treatment of index cases should target the full familial setting. PMID:27149514

  8. Patterns of Drug Resistance Among Tuberculosis Patients in West and Northwestern Iran

    PubMed Central

    Sahebi, Leyla; Ansarin, Khalil; Mohajeri, Parviz; Khalili, Majid; Monfaredan, Amir; Farajnia, Safar; Zadeh, Simin Khayyat

    2016-01-01

    Background: Tuberculosis (TB) is the leading cause of morbidity and mortality among chronic infectious diseases. Objective: The goal of this cross-sectional study (2011-2013;2013) was to examine the patterns of TB drug resistance among HIV-negative pulmonary TB patients in regions near the Iranian border. Method: To this end, MTB isolates were harvested from 300 HIV-negative, pulmonary smear-positive TB patients from the northwest and west Iranian border provinces. Isolates were subjected to first and second-line drug susceptibility testing by the 1% proportion method. Demographic and clinical data were provided using a questionnaire and information from patient records. Results were analyzed using SPSS-18. Results: The mean age of the patients was 52.03 years and 54.3% were male. The prevalence of resistance to any TB drug was 13.6% (38 cases). Eleven percent of the new treatment TB group (28 patients) and 40.7% of the retreatment TB group (11 patients) were resistant to all TB drugs. Twelve (4.3%) patients had multidrug-resistant tuberculosis (MDR-TB) (2.38% in the new TB treatment group and 23.1% in the retreatment group). One patient had extensively drug-resistant tuberculosis (XDR-TB). There was a statistically significant relationship between TB drug resistance and smoking (p=0.02) and a history of migration from village to city (p=0.04), also between TB drug resistance and recurrence of TB in patients that had previously received treatment (p<0.001). Conclusion: Knowledge of drug resistance patterns for new and previously treated cases is critical for effective control of MDR-TB in different regions of the country. The burden of MDR-TB in retreatment cases was high. Previous TB treatment was one of the most important mokers and those who had a history of rural to urban migration were at high risk for the occurrence of TB drug resistance. PMID:27583054

  9. Treatment of multidrug-resistant tuberculosis in a remote, conflict-affected area of the Democratic Republic of Congo.

    PubMed

    Shanks, L; Masumbuko, E W; Ngoy, N M; Maneno, M; Bartlett, S; Thi, S S; Shah, T

    2012-08-01

    The Democratic Republic of Congo is a high-burden country for multidrug-resistant tuberculosis. Médecins Sans Frontières has supported the Ministry of Health in the conflict-affected region of Shabunda since 1997. In 2006, three patients were diagnosed with drug-resistant TB (DR-TB) and had no options for further treatment. An innovative model was developed to treat these patients despite the remote setting. Key innovations were the devolving of responsibility for treatment to non-TB clinicians remotely supported by a TB specialist, use of simplified monitoring protocols, and a strong focus on addressing stigma to support adherence. Treatment was successfully completed after a median of 24 months. This pilot programme demonstrates that successful treatment for DR-TB is possible on a small scale in remote settings. PMID:22565108

  10. Factors Associated with Loss to Follow-up during Treatment for Multidrug-Resistant Tuberculosis, the Philippines, 2012–2014

    PubMed Central

    Garfin, Anna Marie Celina G.; Kurbatova, Ekaterina V.; Mangan, Joan M.; Orillaza-Chi, Ruth; Naval, Leilani C.; Balane, Glenn I.; Basilio, Ramon; Golubkov, Alexander; Joson, Evelyn S.; Lew, Woo-jin; Lofranco, Vivian; Mantala, Mariquita; Pancho, Stuart; Sarol, Jesus N.

    2016-01-01

    To identify factors associated with loss to follow-up during treatment for multidrug-resistant (MDR) tuberculosis (TB) in the Philippines, we conducted a case–control study of adult patients who began receiving treatment for rifampin-resistant TB during July 1–December 31, 2012. Among 91 case-patients (those lost to follow-up) and 182 control-patients (those who adhered to treatment), independent factors associated with loss to follow-up included patients’ higher self-rating of the severity of vomiting as an adverse drug reaction and alcohol abuse. Protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses. These results provide insights for designing interventions aimed at reducing patient loss to follow-up during treatment for MDR TB. PMID:26889786

  11. Transmissibility of Tuberculosis among School Contacts: An Outbreak Investigation in a Boarding Middle School, China

    PubMed Central

    Ma, Mai-Juan; Yang, Yang; Wang, Hai-Bin; Zhu, Yi-Fan; Fang, Li-Qun; An, Xiao-Ping; Wan, Kang-Lin; Whalen, Christopher C.; Yang, Xiao-Xian; Lauzardo, Michael; Zhang, Zhi-Yi; Cao, Jin-Feng; Tong, Yi-Gang; Dai, Er-Hei; Cao, Wu-Chun

    2015-01-01

    Tuberculosis (TB) outbreak occurred in a boarding middle school of China. We explored its probable sources and quantified the transmissibility and pathogenicity of TB. Clinical evaluation, tuberculin skin testing and chest radiography were conducted to identify TB cases. Mycobacterium tuberculosis isolates underwent genotyping analysis to identify the outbreak source. A chain-binomial transmission model was used to evaluate transmissibility and pathogenicity of TB. A total of 46 active cases were ascertained among 258 students and 15 teachers/staff, an attack rate of 16.8%. Genetic analyses revealed two groups of M. tuberculosis cocirculating during the outbreak and possible importation from local communities. Secondary attack rates among students were 4.1% (2.9%, 5.3%) within grade and 7.9% (4.9%, 11%) within class. An active TB case was estimated to infect 8.4 (7.2, 9.6) susceptible people on average. The smear-positive cases were 28 (8, 101) times as infective as smear-negative cases. Previous BCG vaccination could reduce the probability of developing symptoms after infection by 70% (1.4%, 91%). The integration of clinical evaluation, genetic sequencing, and statistical modeling greatly enhanced our understanding of TB transmission dynamics. Timely diagnosis of smear-positive cases, especially in the early phase of the outbreak, is the key to preventing further spread among close contacts. PMID:25757905

  12. Expanding tuberculosis case notification among marginalized groups in Bangladesh through peer sputum collection

    PubMed Central

    McDowell, M.; Hossain, M.; Rahman, N.; Tegenfeldt, K.; Yasmin, N.; Hamilton, C. D.

    2015-01-01

    Case notification rates of tuberculosis (TB) in Bangladesh remain poor despite a high burden of disease. Peer sputum collection among underserved populations was implemented to expand case notification and to provide socially empowering roles in society for often excluded members of marginalized populations. Over the 55 months of the evaluation, 32 587 members of key populations were screened for TB, with 1587 smear-positive TB cases detected. Broadening TB services at human immunodeficiency virus drop-in centers using peer sputum collection to target high-risk populations for TB may be an effective way to increase TB case notification among key populations in Bangladesh. PMID:26400382

  13. Expanding tuberculosis case notification among marginalized groups in Bangladesh through peer sputum collection.

    PubMed

    McDowell, M; Hossain, M; Rahman, N; Tegenfeldt, K; Yasmin, N; Johnson, M G; Hamilton, C D

    2015-06-21

    Case notification rates of tuberculosis (TB) in Bangladesh remain poor despite a high burden of disease. Peer sputum collection among underserved populations was implemented to expand case notification and to provide socially empowering roles in society for often excluded members of marginalized populations. Over the 55 months of the evaluation, 32 587 members of key populations were screened for TB, with 1587 smear-positive TB cases detected. Broadening TB services at human immunodeficiency virus drop-in centers using peer sputum collection to target high-risk populations for TB may be an effective way to increase TB case notification among key populations in Bangladesh. PMID:26400382

  14. Development of Antigen Detection Assay for Diagnosis of Tuberculosis Using Sputum Samples

    PubMed Central

    Pereira Arias-Bouda, Lenka M.; Nguyen, Lan N.; Ho, Ly M.; Kuijper, Sjoukje; Jansen, Henk M.; Kolk, Arend H. J.

    2000-01-01

    The rising incidence of tuberculosis worldwide means an increasing burden on diagnostic facilities, so tests simpler than Ziehl-Neelsen staining are needed. Such tests should be objective, reproducible, and have at least as good a detection limit as 104 bacteria/ml. A capture enzyme-linked immunosorbent assay (ELISA) was developed for detection of lipoarabinomannan (LAM) in human sputum samples. As a capture antibody, we used a murine monoclonal antibody against LAM, with rabbit antiserum against Mycobacterium tuberculosis as a source of detector antibodies. The sensitivity of the capture ELISA was evaluated by using purified LAM and M. tuberculosis whole cells. We were able to detect 1 ng of purified LAM/ml and 104 M. tuberculosis whole cells/ml. LAM could also be detected in culture filtrate of a 3-week-old culture of M. tuberculosis. The culture filtrate contained approximately 100 μg of LAM/ml. The detection limit in sputum pretreated with N-acetyl-l-cysteine and proteinase K was 104 M. tuberculosis whole cells per ml. Thirty-one (91%) of 34 sputum samples from 18 Vietnamese patients with tuberculosis (32 smear positive and 2 smear negative) were positive in the LAM detection assay. In contrast, none of the 25 sputum samples from 21 nontuberculous patients was positive. This specific and sensitive assay for the detection of LAM in sputum is potentially useful for the diagnosis of tuberculosis. PMID:10834989

  15. Treatment Outcomes for Patients with Extensively Drug-Resistant Tuberculosis, KwaZulu-Natal and Eastern Cape Provinces, South Africa.

    PubMed

    Kvasnovsky, Charlotte L; Cegielski, J Peter; van der Walt, Martie L

    2016-09-01

    We analyzed data for a retrospective cohort of patients treated for extensively drug-resistant tuberculosis in 2 provinces in South Africa and compared predictors of treatment outcome in HIV-positive patients who received or had not received antiretroviral drugs with those for HIV-negative patients. Overall, 220 (62.0%) of 355 patients were HIV positive. After 2 years, 34 (10.3%) of 330 patients with a known HIV status and known outcome had a favorable outcome. Multivariate analysis showed that predictors of favorable outcome were negative results for acid-fast bacilli by sputum microscopy at start of treatment and weight >50 kg. HIV-positive patients were more likely to have an unfavorable outcome. The strongest predictor of unfavorable outcome was weight <50 kg. Overall outcomes were poor. HIV status was not a predictor of favorable outcome, but HIV-positive patients were more likely to have an unfavorable outcome. These results underscore the need for timely and adequate treatment for tuberculosis and HIV infection. PMID:27538119

  16. Treatment Outcomes for Patients with Extensively Drug-Resistant Tuberculosis, KwaZulu-Natal and Eastern Cape Provinces, South Africa

    PubMed Central

    Cegielski, J. Peter; van der Walt, Martie L.

    2016-01-01

    We analyzed data for a retrospective cohort of patients treated for extensively drug-resistant tuberculosis in 2 provinces in South Africa and compared predictors of treatment outcome in HIV-positive patients who received or had not received antiretroviral drugs with those for HIV-negative patients. Overall, 220 (62.0%) of 355 patients were HIV positive. After 2 years, 34 (10.3%) of 330 patients with a known HIV status and known outcome had a favorable outcome. Multivariate analysis showed that predictors of favorable outcome were negative results for acid-fast bacilli by sputum microscopy at start of treatment and weight >50 kg. HIV-positive patients were more likely to have an unfavorable outcome. The strongest predictor of unfavorable outcome was weight <50 kg. Overall outcomes were poor. HIV status was not a predictor of favorable outcome, but HIV-positive patients were more likely to have an unfavorable outcome. These results underscore the need for timely and adequate treatment for tuberculosis and HIV infection. PMID:27538119

  17. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB

    PubMed Central

    Barr, David A.; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R.; Sloan, Derek J.

    2016-01-01

    Summary Faster elimination of drug tolerant ‘persister’ bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates ‘persister’ phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli. PMID:27156626

  18. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB.

    PubMed

    Barr, David A; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R; Sloan, Derek J

    2016-05-01

    Faster elimination of drug tolerant 'persister' bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates 'persister' phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli. PMID:27156626

  19. TUBERCULOSIS IN ELEPHANTS: AN UPDATE ON DIAGNOSIS AND TREATMENT; IMPLICATIONS FOR CONTROL IN RANGE COUNTRIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tuberculosis has been detected in captive elephants in the U.S. and Europe (Lewerin 2005; Mikota 2000, 2001; Moller 2005). Culture of samples collected by a trunk wash procedure is the current method of diagnosis. Culture has inherent limitations as a primary diagnostic technique. Failure to isol...

  20. Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis

    PubMed Central

    Bastos, Mayara L.; Hussain, Hamidah; Weyer, Karin; Garcia-Garcia, Lourdes; Leimane, Vaira; Leung, Chi Chiu; Narita, Masahiro; Penã, Jose M.; Ponce-de-Leon, Alfredo; Seung, Kwonjune J.; Shean, Karen; Sifuentes-Osornio, José; Van der Walt, Martie; Van der Werf, Tjip S.; Yew, Wing Wai; Menzies, Dick; Ahuja, S.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E.D.; Chiang, C.Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W.C.M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K.; Flood, J.; Gandhi, N.; Garcia-Garcia, L.; Granich, R.M.; Hollm-Delgado, M.G.; Holtz, T.H.; Hopewell, P.; Iseman, M.; Jarlsberg, L.G.; Keshavjee, S.; Kim, H.R.; Koh, W.J.; Lancaster, J.; Lange, C.; Leimane, V.; Leung, C.C.; Li, J.; Menzies, D.; Migliori, G.B.; Mitnick, C.M.; Narita, M.; Nathanson, E.; Odendaal, R.; O'Riordan, P.; Pai, M.; Palmero, D.; Park, S.K.; Pasvol, G.; Pena, J.; Pérez-Guzmán, C.; Ponce-de-Leon, A.; Quelapio, M.I.D.; Quy, H.T.; Riekstina, V.; Robert, J.; Royce, S.; Salim, M.; Schaaf, H.S.; Seung, K.J.; Shah, L.; Shean, K.; Shim, T.S.; Shin, S.S.; Shiraishi, Y.; Sifuentes-Osornio, J.; Sotgiu, G.; Strand, M.J.; Sung, S.W.; Tabarsi, P.; Tupasi, T.E.; Vargas, M.H.; van Altena, R.; van der Walt, M.; van der Werf, T.S.; Viiklepp, P.; Westenhouse, J.; Yew, W.W.; Yim, J.J.

    2014-01-01

    Background. Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. Methods. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. Results. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. Conclusions. DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis. PMID:25097082

  1. High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

    PubMed Central

    Jindani, Amina; Harrison, Thomas S.; Nunn, Andrew J.; Phillips, Patrick P.J.; Churchyard, Gavin J.; Charalambous, Salome; Hatherill, Mark; Geldenhuys, Hennie; McIlleron, Helen M.; Zvada, Simbarashe P.; Mungofa, Stanley; Shah, Nasir A.; Zizhou, Simukai; Magweta, Lloyd; Shepherd, James; Nyirenda, Sambayawo; van Dijk, Janneke H.; Clouting, Heather E.; Coleman, David; Bateson, Anna L.E.; McHugh, Timothy D.; Butcher, Philip D.; Mitchison, Denny A.

    2014-01-01

    BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and

  2. Nurses' Roles and Experiences with Enhancing Adherence to Tuberculosis Treatment among Patients in Burundi: A Qualitative Study

    PubMed Central

    Carlsson, Marie; Johansson, Stina; Eale, Remy-Paul Bosela

    2014-01-01

    Background. In TB control, poor treatment adherence is a major cause of relapse and drug resistance. Nurses have a critical role in supporting patients in TB treatment process. Yet, very little research has been done to inform policymakers and practitioners on nurses' experiences of treatment adherence among patients with TB. Aim. To describe nurses' experiences of supporting treatment adherence among patients with tuberculosis in Burundi. Method. The study adopted qualitative approach with a descriptive design. A purposive sampling was performed. Eight nurses were selected from two TB treatment centers in Burundi. Content analysis was used to analyze the data. Result. According to the nurses, most patients complete their treatment. Educating patients, providing the medication, observing and following up treatment, and communicating with the patients were the key tasks by nurses to support adherence. Causes for interruption were medication-related difficulties, poverty, and patients' indiscipline. Treatment adherence could also be affected by patients' and nurses' feelings. Providing transportation and meals could enhance treatment compliance. Conclusion. Nurses are critical resources to TB treatment success. In a poverty stricken setting, nurses' work could be facilitated and adherence further could be enhanced if socioeconomic problems (transportation and nutritional support) were alleviated. PMID:25215232

  3. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  4. [Mammary tuberculosis: two cases].

    PubMed

    Hafidi, M R; Kouach, J; Hamidi, L A; Achenani, M; Benchakroun, K; Salek, G; Zoubir, Y; Moussaoui, R D; Dehayni, M

    2011-01-01

    Tuberculosis of the breast is a very rare infection, it occurs chiefly in women of childbearing potential, usually as an apparently primary infection and constitute a diagnosis and therapeutic challenge. Administration of antituberculous agents is the mainstay of therapy. Surgery is required in some cases. We report two cases of breast tuberculosis. The diagnosis was put on histology with good outcome under anti bacillary treatment. Through the literature data we recall the epidemiological, clinical, diagnostic and treatment of this pathology. PMID:22765979