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
Sillah, A.; Togun, T.; Kandeh, S.; Cole, F.; Jallow, A.; Able-Thomas, A.; Hoelscher, M.; Heinrich, N.; Hill, P. C.; Kampmann, B.
Setting: Greater Banjul area of The Gambia. Objectives: To evaluate uptake, adherence and completion of treatment among tuberculosis (TB) exposed children in The Gambia when isoniazid preventive treatment (IPT) is delivered at home Design: Child (age <5 years) contacts of adults with smear-positive TB were prospectively enrolled. Following symptom screening, tuberculin skin testing and clinical evaluation where indicated, those without disease were placed on daily isoniazid, provided monthly at home. Adherence was assessed by pill counts and IsoScreen™ urine test. Results: Of 404 contacts aged <5 years, 368 (91.1%) were offered IPT. Of the 328 (89.4%) for whom consent was received and who commenced IPT, 18 (5.5%) dropped out and 310 (94.5%) remained on IPT to the end of the 6-month regimen. Altogether, 255/328 children (77.7%, 95%CI 73.2–82.2) completed all 6 months, with good adherence. The IsoScreen test was positive in 85.3% (435/510) of all tests among those defined as having good adherence by pill count and in 16% (8/50) of those defined as having poor adherence (P < 0.001). A cascade of care analysis showed an overall completion rate with good adherence of 61% for all child contacts. Conclusion: Home-delivered IPT among child contacts of adults with smear-positive TB in The Gambia achieved verifiable high uptake and adherence rates. System rather than patient factors are likely to determine the success of IPT at national level. PMID:28123958
Egere, U; Sillah, A; Togun, T; Kandeh, S; Cole, F; Jallow, A; Able-Thomas, A; Hoelscher, M; Heinrich, N; Hill, P C; Kampmann, B
Setting: Greater Banjul area of The Gambia. Objectives: To evaluate uptake, adherence and completion of treatment among tuberculosis (TB) exposed children in The Gambia when isoniazid preventive treatment (IPT) is delivered at home Design: Child (age <5 years) contacts of adults with smear-positive TB were prospectively enrolled. Following symptom screening, tuberculin skin testing and clinical evaluation where indicated, those without disease were placed on daily isoniazid, provided monthly at home. Adherence was assessed by pill counts and IsoScreen(™) urine test. Results: Of 404 contacts aged <5 years, 368 (91.1%) were offered IPT. Of the 328 (89.4%) for whom consent was received and who commenced IPT, 18 (5.5%) dropped out and 310 (94.5%) remained on IPT to the end of the 6-month regimen. Altogether, 255/328 children (77.7%, 95%CI 73.2-82.2) completed all 6 months, with good adherence. The IsoScreen test was positive in 85.3% (435/510) of all tests among those defined as having good adherence by pill count and in 16% (8/50) of those defined as having poor adherence (P < 0.001). A cascade of care analysis showed an overall completion rate with good adherence of 61% for all child contacts. Conclusion: Home-delivered IPT among child contacts of adults with smear-positive TB in The Gambia achieved verifiable high uptake and adherence rates. System rather than patient factors are likely to determine the success of IPT at national level.
You, Paul; Aifah, Angela; Abildayev, Tleukhan; Akilzhanova, Ainur; Kozhamkulov, Ulan; Muminov, Talgat; Darisheva, Meruert; Zhussupov, Baurzhan; Terlikbayeva, Assel; El-Bassel, Nabila; Schluger, Neil
Background Sputum smear-positive tuberculosis (TB) patients have a high risk of transmission and are of great epidemiological and infection control significance. Little is known about the smear-positive populations in high TB burden regions, such as Kazakhstan. The objective of this study is to characterize the smear-positive population in Kazakhstan and identify associated modifiable risk factors. Methods Data on incident TB cases’ (identified between April 2012 and March 2014) socio-demographic, risk behavior, and comorbidity characteristics were collected in four regions of Kazakhstan through structured survey and medical record review. We used multivariable logistic regression to determine factors associated with smear positivity. Results Of the total sample, 193 (34.3%) of the 562 study participants tested smear-positive. In the final adjusted multivariable logistic regression model, sex (adjusted odds ratio (aOR) = 2.0, 95% CI:1.3–3.1, p < 0.01), incarceration (aOR = 3.6, 95% CI:1.2–11.1, p = 0.03), alcohol dependence (aOR = 2.6, 95% CI:1.2–5.7, p = 0.02), diabetes (aOR = 5.0, 95% CI:2.4–10.7, p < 0.01), and physician access (aOR = 2.7, 95% CI:1.3–5.5p < 0.01) were associated with smear-positivity. Conclusions Incarceration, alcohol dependence, diabetes, and physician access are associated with smear positivity among incident TB cases in Kazakhstan. To stem the TB epidemic, screening, treatment and prevention policies should address these factors. PMID:28249005
Kruyt, M. L.; Kruyt, N. D.; Boeree, M. J.; Harries, A. D.; Salaniponi, F. M.; van Noord, P. A.
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
Zhang, Tao; Du, Jian; Yin, Xiaoyan; Xue, Fuzhong; Liu, Yanxun; Li, Runzi; Luo, Cheng; Li, Liang; Li, Xiujun
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
Zhang, Tao; Du, Jian; Yin, Xiaoyan; Xue, Fuzhong; Liu, Yanxun; Li, Runzi; Luo, Cheng; Li, Liang; Li, Xiujun
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.
Mahishale, Vinay; Avuthu, Sindhuri; Patil, Bhagyashri; Lolly, Mitchelle; Eti, Ajith; Khan, Sujeer
Background: There is growing evidence that diabetes mellitus (DM) is an important risk factor for tuberculosis (TB). A significant number of DM patients have poor glycemic control. This study was carried out to find the impact of poor glycemic control on newly diagnosed smear-positive pulmonary tuberculosis patients with type-2 diabetes mellitus in a tertiary care hospital. Methods: In a hospital-based prospective study, newly diagnosed smear-positive pulmonary TB with DM patients were classified as poorly controlled diabetes (HBA1C≥7%) and optimal control diabetics (HbA1c<7%). Patients were started on anti-TB treatment and followed for 2 years for severity and treatment outcome. ANOVA was used for numerical variables in the univariable analysis. Logistic regression analysis was used for multivariable analysis of treatment outcome. The significance level was kept at a P≤0.05. Results: A total of 630 individuals who met the inclusion criteria were analyzed; of which 423 patients had poor glycemic control (PGC) and 207 patients had optimal glycemic control (OGC). The average HbA1c was 10±2.6 and 5±1.50 in the PGC and OGC groups, respectively. The mean symptom score was significantly higher in the PGC group compared with patients in the OGC group (4.55±0.80 vs. 2.70±0.82, P<0.001). PGC was associated with more extensive lung disease, lung cavitation, and positive sputum smear at the baseline. In PGC, sputum smears were significantly more likely to remain positive after 2 months of treatment. PGC patients had significantly higher rates of treatment failure (adj. OR 0.72, 95% CI 0.58-0.74, P<0.001) and relapse (adj. OR 2.83, 95% CI 2.60-2.92, P<0.001). Conclusion: Poor glycemic control is associated with an increased risk of advanced and more severe TB disease in the form of lung cavitations, positive sputum smear, and slower smear conversion. It has a profound negative effect on treatment completion, cure, and relapse rates in patients with pulmonary
Sahebi, Leyla; Ansarin, Khalil; Hoffner, Sven; Mohajeri, Parviz; Mohammadi, Abolghasem
Background: Tuberculosis (TB) is the leading cause of morbidity and mortality among chronic infectious diseases. The goal of this cross-sectional study (2012–2014) was to examine the prevalence of Mycobacterium TB (MTB) Beijing strains in regions near the Iranian border and to identify any epidemiological links. Materials and Methods: To this end, MTB isolates were harvested, from 64 HIV-negative, pulmonary smear-positive TB patients from the Iranian border provinces of East Azerbaijan (North-West), Kurdistan (West), and Kermanshah (West) (2012–2014). Isolates were subjected to restriction fragment length polymorphism (RFLP) analysis, using the insertion sequence IS6110 as a probe (IS6110 RFLP), and drug susceptibility testing by the proportion method. We gathered demographic and clinical data using a questionnaire and reviewing patient records. Results were analyzed with Gel Compare II 6.6 and SPSS-18. Results: The mean age of the patients was 54.4 years and 46.9% were male. The prevalence of Beijing strains among the isolates was 9.4% (17.6% in the Western provinces and 0% in East Azerbaijan). There was a statistically significant relationship between the Beijing strains and drug resistance and also between these strains, and the recurrence of TB in patients that had previously received treatment (P = 0.02 and P = 0.04, respectively). Conclusions: Finally, the prevalence of Beijing strains in Western Iran was greater than expected. Our results therefore indicate that regional and cross-border tracing may be necessary to control spread of this organism. PMID:28028521
Reza, L W; Satyanarayana, S; Pandey, A; Kumar, S; Devendrappa, N M; Anand, L; Singh, G; Kumar, A M V; Chadha, S S; Wilson, N; Sachdeva, K S; Nair, S A
In July 2012, light-emitting diode fluorescence microscopy (LED-FM) replaced conventional light microscopy using Ziehl-Neelsen stain in the detection of sputum-positive pulmonary tuberculosis in 190 microscopy centres of medical colleges operating under India's Revised National Tuberculosis Control Programme. We compared the performance of LED-FM (July-December 2012) to that of conventional microscopy (July-December 2011) across 190 sites. Of 222 658 patients examined using conventional microscopy, 28 042 (12.6%) were smear-positive, while of 224 714 examined using LED-FM, 33 552 (14.9%) were smear-positive, an additional yield of 5251 cases after adjusting for the increase in patients examined. We recommend replacing conventional microscopy with LED-FM in high workload microscopy centres in India.
Bhardwaj, Ashok Kumar; Kashyap, Surender; Bansal, Pradeep; Kumar, Dinesh; Raina, Sunil Kumar; Chander, Vishav; Sharma, Sushant
Early case identification and prompt treatment of new sputum smear positive case are important to reduce the spread of tuberculosis (TB). Present study was planned to study the associated factors for duration to contact the health facility since appearance of symptoms and treatment default. Methodology. It was prospective cohort study of TB patients already registered for treatment in randomly selected TB units (TUs) in Himachal Pradesh, India. Relative risk (RR) was calculated as risk estimate to find out the explanatory variables for early contact and default. Results. Total 1607 patients were recruited and 25 (1.5%) defaulted treatment. Patients from nuclear family (aRR: 1.37; 1.09-1.73), ashamed of TB (aRR: 1.32; 1.03-1.70), wishing to disclose disease status (aRR: 1.79; 1.43-2.24), but aware of curable nature (aRR: 1.67; 1.17-2.39) and preventable (aRR: 1.35; 1.07-1.70) nature of disease, contacted health facility early since appearance of symptoms. Conclusion. Better awareness and less misconceptions about disease influences the early contact of health facility and low default rate in North India.
Brhane, Mussie; Kebede, Ameha; Petros, Yohannes
Background Molecular methods that target drug resistance mutations are suitable approaches for rapid drug susceptibility testing to detect multidrug-resistant tuberculosis (MDR-TB). The aim of the study was to determine MDR-TB cases and to analyze the frequency of gene mutations associated with rifampicin (RIF) and/or isoniazid (INH) resistance of Mycobacterium tuberculosis among smear-positive pulmonary tuberculosis patients. Methods Institution-based cross-sectional study design was employed. Sputum specimens were collected, and using a pretested questionnaire, data for associated risk factors for drug resistance were collected from 105 consecutive smear-positive pulmonary tuberculosis patients in Karamara General Hospital. Specimens were transported to Harar Health Research and Regional Laboratory, Harar, where molecular drug susceptibility testing was performed using GenoType® MTBDRplus assay. Results Of the total 105 sputum specimens, 98 (93.3%) gave interpretable results, in which 67 (68.4%) were new cases and 31 (31.6%) were previously treated cases. Of these, 80 (81.6%) were sensitive to both drugs and 18 (18.4%) were resistant to RIF and/or INH. The prevalences of MDR-TB in total cases, new, and previously treated cases were 10 (10.2%), 3 (4.5%), and 7 (22.6%), respectively. Among the ten total RIF-resistant specimens, eight (80%) had resulted because of absence of rpoB WT8 and presence of MUT3 and in all specimens, the amino acids changed were Ser531Lue. Of the 18 total INH-resistant specimens, 15 (83.3%) had mutations in the katG gene (katG MUT1, Ser315Thr1), indicating high-level resistance, while 3 (14.7%) had mutations in the inhA promoter gene (Cys15Thr), indicating low-level resistance. Conclusion Among the mutations associated with resistance to RIF and INH, the majority were in codon 531 of the rpoB gene and codon 315 of the katG gene. Relatively high prevalence of MDR-TB was observed in the study. PMID:28331348
Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.
Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low. PMID:27695680
Lin, Y; Chiang, C-Y; Rusen, I D; Hinderaker, S G; Roldan, A; Heldal, E; Enarson, D A; Zhang, L-X
Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low.
Afutu, F K; Zachariah, R; Hinderaker, S G; Ntoah-Boadi, H; Obeng, E Apori; Bonsu, F Adae; Harries, A D
Sputum smear-positive TB patients, diagnosed in the laboratory, who never start anti-TB treatment are classified as 'initial defaulters'. In Ridge Hospital, Accra, Ghana, there were 84 laboratory confirmed TB cases in 2009, of whom 32 (38%) were initial defaulters. Cure and default rates based on this cohort were 54% and 43% respectively, compared with rates of 87% and 8% when using the cohort based on 52 patients registered for treatment. This study highlights the problem of initial defaulters, and shows that programme performance may be poor when patients in laboratory registers are used as the cohort to evaluate treatment outcomes.
Khazaei, Salman; Soheilyzad, Mokhtar; Molaeipoor, Leila; Khazaei, Zaher; Rezaeian, Shahab; Khazaei, Somayeh
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
Tessema, Belay; Beer, Joerg; Emmrich, Frank; Sack, Ulrich; Rodloff, Arne C.
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
Schön, T; Idh, J; Westman, A; Elias, D; Abate, E; Diro, E; Moges, F; Kassu, A; Ayele, B; Forslund, T; Getachew, A; Britton, S; Stendahl, O; Sundqvist, T
In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69-3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p < 0.01). A low baseline eNO (<10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies.
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
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.
Chikobvu, Perpetual; Heunis, James Christoffel; van der Merwe, Sonja
Little is known about the drivers of two-month sputum smear non-conversion in the South African context. Our study sought to determine these factors in new sputum smear positive tuberculosis (TB) patients in South Africa’s Free State Province. A retrospective record review was conducted for all TB patients on treatment between 2003 and 2009. Two-month sputum smear non-conversion was defined by a positive sputum smear result. Data was subjected to univariate, bivariate and regression analyses. Generalized linear regression models were used to estimate the risk for two-month sputum smear non-conversion. Age, pre-treatment sputum smear grading, HIV status and TB disease classification influenced two-month sputum smear non-conversion. Significant associations were thus established between health systems, microbiological, clinical and demographic factors, and two-month sputum smear non-conversion. This study provides program managers with evidence to support the development of more tailored TB care. PMID:28299125
Ormerod, L P; Green, R M; Broadfield, E
The effects of the policy change in X-ray follow-up of adult tuberculin-positive close contacts of sputum microscopy positive pulmonary tuberculosis made by the Joint Tuberculosis Committee of the British Thoracic Society in 2000 were monitored prospectively from late 2000 until the end of 2003. No cases in contacts that could have been detected by interval X-rays at three and 12 months were found. The data, on 291 cases, support the abandonment of X-ray follow-up in favour of an 'inform and advise' strategy after an initial normal chest X-ray in this category of tuberculosis contact.
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Patel, J; Dave, P; Satyanarayana, S; Kumar, A M V; Shah, A; Ananthakrishnan, R; Ratnu, A
In Ahmedabad, India, a retrospective record review was undertaken among 2842 sputum smear-positive tuberculosis patients registered for treatment from April to September 2011 to assess the association of pretreatment sputum smear grade with sputum positivity and the additional yield of a second sputum sample during each follow-up examination. Respectively 39%, 26%, 28% and 7% of patients had pretreatment sputum grade 3+, 2+, 1+ and scanty. The higher the pretreatment sputum grade, the higher the proportion found positive during various follow-up periods. Overall, the additional yield of the second sputum sample was <2%; it did not vary with pretreatment smear grading.
Zhang, Z X; Sng, L-H; Yong, Y; Lin, L M; Cheng, T W; Seong, N H; Yong, F K
Diagnostic and treatment delays increase the severity and transmission of pulmonary tuberculosis (PTB). This study aimed to evaluate TB diagnostic and treatment delays in acid-fast bacilli (AFB) smear-negative patients.
This was a retrospective observational study. Patients with positive AFB culture of Mycobacterium tuberculosis complex (MTC) were selected from among hospitalised patients with a diagnosis of pneumonia. Admission ward, anti-tuberculosis treatment and the duration of AFB culture were compared between smear-positive and smear-negative patients.
Of the 70 patients with positive isolation of MTC in AFB culture, 27 (38.5%) were smear-negative; of these, 18 (66.7%) were not isolated while in hospital, and 17 (63%) were neither diagnosed nor treated for TB. In contrast, 41 of the 43 smear-positive patients (95.3%) were directly admitted or quickly transferred to the isolation room and started on anti-tuberculosis treatment (P < 0.001). Samples from smear-negative patients required more time to grow MTC in AFB culture than those of smear-positive patients (23 days vs. 14 days, P < 0.001). Diabetes was significantly associated with AFB smear positivity, with an odds ratio of 12.2.
Negative AFB smears caused significant diagnostic and treatment delay. Patients staying in the general ward were exposed to TB patients who were not diagnosed in time.
Enarson, D. A.; Chiang, C-Y.; Rusen, I. D.; Qiu, L-X.; Kan, X-H.; Yuan, Y-L.; Du, J.; Zhang, T-H.; Li, Y.; Li, X-F.; Du, C-T.; Zhang, L-X.
Objective: 1) To assess patient delay among new smear-positive pulmonary tuberculosis (PTB) patients in accessing health services in seven FIDELIS (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) projects from 2003 to 2008 in China; 2) to compare treatment delay by province; and 3) to assess factors associated with delay. Method: Records of new smear-positive PTB patients were reviewed. Data sources were the consultation book, laboratory register, patient record, treatment card and the PWLAHS (people with limited access to health services) evaluation form. Data were collected using a standard questionnaire, cross-checked by staff from the sites and by the International Union Against Tuberculosis and Lung Disease (The Union) and analysed by The Union. Results: Of the 75 401 new smear-positive PTB patients included in the study, 63–89% were PWLAHS. The average gross domestic product of the project sites and at national level were respectively US$557 and US$998. The median patient delay was 93 days (range 68–128). Delays were longer among females, older patients, rural residents and PWLAHS. Delayed access to health services was significantly associated with a greater number of symptoms. Conclusion: Patient delay in accessing health care in China was lengthy; TB care and control needs to be improved. PMID:26400603
Tessema, Belay; Muche, Abebe; Bekele, Assegedech; Reissig, Dieter; Emmrich, Frank; Sack, Ulrich
Background In Gondar University Teaching Hospital standardized tuberculosis prevention and control programme, incorporating Directly Observed Treatment, Short Course (DOTS) started in 2000. According to the proposal of World Health Organization (WHO), treatment outcome is an important indicator of tuberculosis control programs. This study investigated the outcome of tuberculosis treatment at Gondar University Teaching Hospital in Northwest Ethiopia. Methods We analyzed the records of 4000 tuberculosis patients registered at Gondar University Teaching Hospital from September 2003 to May 2008. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control program guideline. Multivariate analysis using logistic regression model was used to analyse the association between treatment outcome and potential predictor variables. Results From the total of 4000 patients, tuberculosis type was categorized as extrapulmonary in 1133 (28.3%), smear negative pulmonary tuberculosis in 2196 (54.9%) and smear positive pulmonary tuberculosis in 671 (16.8%) cases. Of all patients, treatment outcome was classified as successfully treated in 1181(29.5%), defaulted in 730 (18.3%), died in 403 (10.1%), treatment failed in six (0.2%) and transferred out in 1680 (42.0%) patients. Males had the trend to be more likely to experience death or default than females, and the elderly were more likely to die than younger. The proportion of default rate was increased across the years from 97(9.2%) to 228(42.9%). Being female, age group 15-24 years, smear positive pulmonary tuberculosis and being urban resident were associated with higher treatment success rate. Conclusion The treatment success rate of tuberculosis patients was unsatisfactorily low (29.5%). A high proportion of patients died (10.1%) or defaulted (18.3%), which is a serious public health concern that needs to be addressed urgently. PMID:19799801
Evaluation of the treatment outcome by the cohort analysis method is an important part of tuberculosis (TB) control. In the Japanese TB surveillance system, the treatment outcome is automatically classified by computer according to a pre-set algorithm, so the treatment outcome is evaluated very rigidly. In the case of new sputum smear positive pulmonary TB cases (n = 8,999) newly notified in 2008, the patients' treatment outcomes based on the annual report 2009 database were as follows: "success," which combined "cured" and "completed," was 47.7%, "died" was 19.1%, "failed" was 1.1%, "defaulted" was 3.8%, "transferred out" was 2.8%, "on treatment after 12 months" was 11.8% and "not evaluated" was 13.6%. In addition to evaluation of the treatment outcome by the cohort method, the proportion of deaths was observed among all forms of TB patients (n = 24,571) who were newly registered in 2008. In total, 17.3% of all forms of TB cases died within one year after the beginning of treatment. The proportion corresponding to this was 23.7% for new sputum smear positive pulmonary TB and 23.5% for re-treatment sputum smear positive pulmonary TB. Among the new sputum smear positive pulmonary TB patients (n = 2,136) who died within one year after the beginning of treatment, 37.0% of them died within one month after the beginning of treatment, 51.6% died within two months and 61.9% died within three months.
Chikamatsu, Kinuyo; Aono, Akio; Kato, Tomoko; Takaki, Akiko; Yamada, Hiroyuki; Sasaki, Yuka; Izumi, Kiyohiko; Yi, Lina; Mitarai, Satoshi
We investigated the correlation between the cycle threshold (Ct) value of the COBAS(®) TaqMan(®) MTB (TaqMan MTB), the mycobacterial smear positivity grade, and the time to detection (TTD) in the Mycobacteria Growth Indicator Tube (MGIT) for quantification of Mycobacterium tuberculosis (MTB). For 57 sputum samples, significant correlations were observed between the Ct value, the smear positivity grade, and the MGIT TTD (Spearman's rank correlation coefficient: r(s) = -0.940, P < 0.001 and Pearson's correlation coefficient: r(p) = 0.737, P < 0.001). In addition, a correlation was observed between the number of bacteria estimated based on the smear positivity grade and the number of MTB bacilli calculated by the Ct value (r(s) = 0.930, P < 0.001). This study has demonstrated the possible estimation of the smear positivity grade and MGIT TTD using the Ct value of TaqMan MTB, which is based on a real-time PCR system, for diagnostic samples.
Background Several FIDELIS projects (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) in Tanzania were conducted by the National Tuberculosis and Leprosy Programme (NTLP) during the years 2004-2008 to strengthen diagnostic and treatment services. These projects collected information on treatment delay and some of it was available for research purposes. With this database our objective was to assess the duration and determinants of treatment delay among new smear positive pulmonary tuberculosis (TB) patients in FIDELIS projects, and to compare delay according to provider visited prior to diagnosis. Methods Treatment delay among new smear positive TB patients was recorded for each patient at treatment initiation and this information was available and fairly complete in 6 out of 57 districts with FIDELIS projects enrolling patients between 2004 and 2007; other districts had discarded their forms at the time of analysis. It was analysed as a cross sectional study. Results We included 1161 cases, 10% of all patients recruited in the FIDELIS projects in Tanzania. Median delay was 12 weeks. The median duration of cough, weight loss and haemoptysis was 12, 8 and 3 weeks, respectively. Compared to Hai district Handeni had patients with longer delays and Mbozi had patients with shorter delays. Urban and rural patients reported similar delays. Patients aged 15-24 years and patients of 65 years or older had longer delays. Patients reporting contact with traditional healers before diagnosis had a median delay of 15 weeks compared to 12 weeks among those who did not. Patients with dyspnoea and with diarrhoea had longer delays. Conclusion In this patient sample in Tanzania half of the new smear positive pulmonary tuberculosis patients had a treatment delay longer than 12 weeks. Delay was similar in men and women and among urban and rural patients, but longer in the young and older age groups. Patients using traditional healers had a 25% longer median delay
Khanna, A; Lohya, S; Sharath, B N; Harries, A D
Diabetes mellitus (DM) is known to increase the risk of tuberculosis (TB) and adversely affect TB treatment outcomes. A descriptive study was carried out in registered TB patients screened for DM at Lok Nayak Hospital, New Delhi, India. Of 458 TB patients, 66 (14%) had DM. In those with dual disease, age ≥40 years, smear-positive pulmonary TB and recurrent TB were significantly more common. There was no effect of DM on TB treatment outcomes, although there was a trend towards smear non-conversion at 2 months. Screening for DM works well, and certain patient characteristics are more common in those with dual disease.
Sawadogo, Bernard; Tint, Khin San; Tshimanga, Mufuta; Kuonza, Lazarus; Ouedraogo, Laurent
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
Evaluation of the outcome of treatment by the cohort analysis method is an important aspect of TB control. In the Japanese tuberculosis (TB) surveillance system, the outcome of treatment is automatically classified by computer according to the order of pre-set algorithm, so the treatment outcome is evaluated very rigidly. Although treatment outcomes are classified roughly into the eight categories of "cured", "completed", "died", "failed", "defaulted", "transferred", "still on treatment" and "not evaluated", there are actually 15 categories in our surveillance system; each category of "completed", "defaulted", and "still on treatment" has two subcategories and "not evaluated" has five subcategories. In the case of new sputum smear positive pulmonary cases (n=9,421) newly notified in 2007, their treatment outcome was as follows; "success" which combined "cured" and "completed" was 45.5%, "died" was 18.4%, "failed" was 1.0%, "defaulted" was 5.0%, "transferred" was 3.2%, "still on treatment" was 12.0% and "not evaluated" was 14.9%. Among the 5.0% who were classified as "defaulted", 0.7% was due to treatment interruption for more than consecutive 60 days or 2 months, and 4.3% was due to premature treatment cessation of any causes. The category "not evaluated" includes those who died before beginning treatment, those whose initial treatment regimen is unknown, those whose treatment is other than standard treatment, those who stopped INH and/or RFP before treatment completion, and those whose information is insufficient for classifying treatment outcome. In addition to evaluation of treatment outcome by the cohort method, the proportion of deaths was observed among all forms of TB patients (n = 25,184) and new sputum smear positive pulmonary patients (n=9421) who were newly registered in 2007. 16.4% of all forms of TB cases and 22.5% of new sputum smear positive pulmonary cases died within one year after beginning of treatment. Among new sputum smear positive pulmonary
Zhang, HaiYang; Ehiri, John; Yang, Huan; Tang, Shenglan; Li, Ying
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
Heysell, Scott K; Mtabho, Charles; Mpagama, Stellah; Mwaigwisya, Solomon; Pholwat, Suporn; Ndusilo, Norah; Gratz, Jean; Aarnoutse, Rob E; Kibiki, Gibson S; Houpt, Eric R
Low antituberculosis (TB) drug levels are common, but their clinical significance remains unclear, and methods of measurement are resource intensive. Subjects initiating treatment for sputum smear-positive pulmonary TB were enrolled from Kibong'oto National TB Hospital, Tanzania, and levels of isoniazid, rifampin, ethambutol, and pyrazinamide were measured at the time of typical peak plasma concentration (C(2 h)). To evaluate the significance of the effect of observed drug levels on Mycobacterium tuberculosis growth, a plasma TB drug activity (TDA) assay was developed using the Bactec MGIT system. Time to detection of plasma-cocultured M. tuberculosis versus time to detection of control growth was defined as a TDA ratio. TDA assays were later performed using the subject's own M. tuberculosis isolate and C(2 h) plasma from the Tanzanian cohort and compared to drug levels and clinical outcomes. Sixteen subjects with a mean age of 37.8 years ± 10.7 were enrolled. Fourteen (88%) had C(2 h) rifampin levels and 11 (69%) had isoniazid levels below 90% of the lower limit of the expected range. Plasma spiked with various concentrations of antituberculosis medications found TDA assay results to be unaffected by ethambutol or pyrazinamide. Yet with a range of isoniazid and rifampin concentrations, TDA exhibited a statistically significant correlation with drug level and drug MIC, and a TDA of ~1.0 indicated the presence of multidrug-resistant TB. In Tanzania, low (≤ 2.0) TDA was significantly associated with both lower isoniazid and rifampin C(2 h) levels, and very low (≤ 1.5) TDA corresponded to a trend toward lack of cure. Study of TDA compared to additional clinical outcomes and as a therapeutic management tool is warranted.
Guwatudde, David; Zalwango, Sarah; Kamya, Moses R.; Debanne, Sara M.; Diaz, Mireya I.; Okwera, Alphonse; Mugerwa, Roy D.; King, Charles; Whalen, Christopher C.
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
Blomberg, B.; Spinaci, S.; Fourie, B.; Laing, R.
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
Background At present, much of the attention within tuberculosis (TB) management is spent on microbiological cure, and its impact on health-related quality of life (HRQoL) is either undervalued or seldom considered. The aim of this study was to evaluate the impact of TB treatment on HRQoL of new smear positive pulmonary tuberculosis (PTB) patients. Moreover, we also aimed to determine whether the selected socio-demographic and clinical variables were predictive of variability in the HRQoL scores over time. Methods This was a prospective follow-up of new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. All eligible patients (i.e., a new case of smear positive PTB, literate and aged 18 years or above) were asked to self-complete the SF-36v2 questionnaire at the start of their treatment, and then subsequently after the intensive phase and at the end of the treatment. A score on a health domain or component summary measure that was less than 47 norm-based scoring (NBS) point was considered indicative of impaired function within that health domain or dimension. Likewise, an individual having mental component summary (MCS) score ≤ 42 NBS point was considered to be at the risk of depression. Repeated measures ANOVA test was performed to examine how the summary scores varied over time, and to determine whether independent variables were predictive of variability in the physical component summary (PCS) and MCS scores over time. Results A total of 216 patients completed the SF-36v2 questionnaire at the start of their treatment. Out of these, 177 and 153 completed the questionnaire at the second and third follow-ups, respectively. The mean PCS scores at the start of the treatment, after the intensive phase and at the end of treatment were 41.9 (SD 5.1), 45.8 (SD 4.8) and 46.0 (SD 6.9), respectively. Similarly, the mean MCS scores at the start of the treatment, after the intensive phase
The fight against tuberculosis in the German Democratic Republic was performed from the very beginning as a task of the state and the society; it was developed according to the progress of economic possibilities and the epidemiological situation. The contribution of the community and of the social-economic development on tuberculosis epidemiology has proved to be decisively important factors in tuberculosis control. The specific methods applied in tuberculosis control in the course of more than 30 years have changed in their importance effectiveness and efficiency with the reduction of the tuberculosis problem and the development of new techniques. Therefore a continuous evaluation of the tuberculosis situation is necessary to recognize the most effective approach. By reducing the estimated annual infection rate to less than 0.05%, the incidence of smear positive pulmonary tuberculosis to less than 5/100,000 and the practical disappearance of tuberculosis among children tuberculosis has become an endemic localized disease among predominantly old citizens. People's mass x-ray examinations have considerably lost their value for finding tuberculosis. Early coverage and examination of persons with respiratory symptoms (21-days-coughers), of contact persons and high risk groups will determine the future activities of the chest clinics. Their integration into the system of outpatient clinics and the system of primary health care were an important step on this way. Successful treatment of each case of tuberculosis is now possible and must be attained. Early case finding + treatment considered as an united activity has become the decisively important measure in the control of tuberculosis. The endemic foci of tuberculosis in some communities have to be surveyed and eliminated with priority. Moreover, the cooperation of all physicians of public health is necessary. Only by this way tuberculosis can be eradicated in GDR in a defined time. (Aim of WHO and IUaT: 1 case of
Abuaku, Benjamin; Tan, Hongzhuan; Li, Xingli; Chen, Mengshi; Huang, Xin
We used the 2005 and 2006 national surveillance data to elucidate some of the risk factors for treatment default and death among tuberculosis (TB) patients in Hunan, China. Risk of default was higher in males (odds ratio (OR) 1.25; 95% confidence interval (CI) 1.08, 1.44); lowest in patients aged 15-24 y (OR 0.60; 95% CI 0.49, 0.75), and generally increased with increasing age; lower in patients living in cities with per capita gross domestic product (GDP) of less than 1000 US$ (OR 0.60, 95% CI 0.49, 0.72), and increased with increasing per capita GDP of city of residence; and higher in patients with previously treated smear-positive pulmonary TB (diagnostic category II according to the World Health Organization definition; OR 1.99; 95% CI 1.22, 3.23). Risk of death was lowest in patients aged 15-24 y (OR 0.07; 95% CI 0.05, 0.10), and increased with increasing age; lower in new cases (OR 0.50; 95% CI 0.33, 0.76); and highest in patients who treated themselves (OR 3.47; 95% CI 1.27, 9.46). We conclude that male TB patients, elderly TB patients, patients resident in cities with higher per capita GDP, and patients receiving category II treatment need special attention to reduce TB treatment default in the province. Furthermore, elderly TB patients and patients with a long history of TB need special attention to reduce mortality. Self-treatment also needs to be discouraged to reduce mortality.
Doulougou, B; Kouanda, S; Nikiéma, L; Ouédraogo, G; Tiendrébeogo, S; Sondo, B; Greenwell, F; Salomon, J A
A cross-sectional study was initiated in Burkina Faso's National Tuberculosis Programme to confirm successful treatment results within 3 months of completing treatment and to characterise longer-term outcomes 12-24 months after completion. The sample (n = 278) included 91 patients who had completed treatment 0-3 months earlier ('short-term' sample) and 187 patients who had completed treatment 12-24 months earlier ('long-term' sample). All sputum specimens from the short-term sample were confirmed as negative. In the long-term sample, among 154 patients with available information, 13 (8%) had died, 24 were not traced, and 117 (76%) were interviewed and had sputum examinations, of which 2 (2%) were smear-positive. Recording of successful treatment outcomes shows good validity.
Seung, K J; Bai, G H; Kim, S J; Lew, W J; Park, S K; Kim, J Y
South Korea's complex system of tuberculosis control has never been fully described. The prevalence of tuberculosis has dropped dramatically since 1965, partly because of farsighted governmental policy that provided low-cost, accessible tuberculosis treatment to the entire population. Within the tuberculosis control system, public and private sector entities provide a wide variety of treatment options. The National Tuberculosis Program focuses on improving cure rates for new cases, while the private sector has taken more of a role in the treatment of drug-resistant tuberculosis and other types of complicated cases. There has been a decrease in drug-resistant tuberculosis since 1980 for multiple reasons, including increased cure rates from the introduction of rifampin-based regimens, improved nutrition and living standards, and the treatment of drug-resistant cases in the private sector. Multidrug-resistant tuberculosis, however, still poses a significant threat to public health. The limited outcomes data that exist in South Korea for multidrug-resistant tuberculosis treatment suggest that cure rates are low and failure and abandonment rates are high. New public health measures are needed to improve the control of multidrug-resistant tuberculosis.
Rodger, Alison J.; Toole, Mike; Lalnuntluangi, Baby; Muana, V.; Deutschmann, Peter
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
Anuwatnonthakate, Amornrat; Limsomboon, Pranom; Nateniyom, Sriprapa; Wattanaamornkiat, Wanpen; Komsakorn, Sittijate; Moolphate, Saiyud; Chiengsorn, Navarat; Kaewsa-ard, Samroui; Sombat, Potjaman; Siangphoe, Umaporn; Mock, Philip A.; Varma, Jay K.
Background The World Health Organization (WHO) recommends that tuberculosis (TB) patients receive directly observed therapy (DOT). Randomized controlled trials have not consistently shown that this practice improves TB treatment success rates. In Thailand, one of 22 WHO-designated high burden TB countries, patients may have TB treatment observed by a health care worker (HCW), family member, or no one. We studied whether DOT improved TB treatment outcomes in a prospective, observational cohort. Methods and Findings We prospectively collected epidemiologic data about TB patients treated at public and private facilities in four provinces in Thailand and the national infectious diseases hospital from 2004–2006. Public health staff recorded the type of observed therapy that patients received during the first two months of TB treatment. We limited our analysis to pulmonary TB patients never previously treated for TB and not known to have multidrug-resistant TB. We analyzed the proportion of patients still on treatment at the end of two months and with treatment success at the end of treatment according to DOT type. We used propensity score analysis to control for factors associated with DOT and treatment outcome. Of 8,031 patients eligible for analysis, 24% received HCW DOT, 59% family DOT, and 18% self-administered therapy (SAT). Smear-positive TB was diagnosed in 63%, and 21% were HIV-infected. Of patients either on treatment or that defaulted at two months, 1601/1636 (98%) patients that received HCW DOT remained on treatment at two months compared with 1096/1268 (86%) patients that received SAT (adjusted OR [aOR] 3.8; 95% confidence interval [CI] 2.4–6.0) and 3782/3987 (95%) patients that received family DOT (aOR 2.1; CI, 1.4–3.1). Of patients that had treatment success or that defaulted at the end of treatment, 1369/1477 (93%) patients that received HCW DOT completed treatment compared with 744/1074 (69%) patients that received SAT (aOR 3.3; CI, 2.4–4.5) and
Samuel, Blesson; Volkmann, Tyson; Cornelius, Sushma; Mukhopadhay, Sugata; MejoJose; Mitra, Kaushik; Kumar, Ajay M. V.; Oeltmann, John E.; Parija, Sidhajyoti; Prabhakaran, Aslesh Ottapura; Moonan, Patrick K.; Chadha, Vineet K.
Introduction Poverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome. Methods This was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death). Results Of 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51; 95% Confidence Intervals: 0.30 - 0.86). Conclusion Under programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line. PMID:28042591
Tuberculosis is one of the most important health problems worldwide. In developed countries there is an increased number of cases due to different reasons. The most likely determinant cause is from immigrants coming from high endemic areas. This phenomenon is a direct cause of the increase in extrapulmonary and complicated pulmonary forms of tuberculosis. There are only a few controlled clinical trials evaluating therapies for extrapulmonary tuberculosis. Consequently, documented evidence is scarce, particularly in paediatrics. The majority of therapeutic recommendations are based on series of cases or expert opinions, with a lack of uniformity provided by the different consensus of the main scientific societies. The main objective of this fourth consensus by the Tuberculosis Study Group of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediátrica, SEIP) is to perform a thorough revision of the data obtained from scientific literature, in order to establish recommendations for the treatment of extrapulmonary tuberculosis and complicated forms of pulmonary tuberculosis, adapted to the characteristics and drugs available in Spain.
Assefzadeh, M; Barghi, R Gh; Shahidi, Sh S
As a part of a comprehensive programme of tuberculosis (TB) control in the central prison in Qazvin, Islamic Republic of Iran, a programme of active case-finding was carried out from February 2004 to July 2005. From the 768 prisoners examined, 41 (5.3%) were suspected of TB and gave sputum samples. A total of 7 smear-positive TB cases were found, giving a TB prevalence in the prison of 910 per 100,000, 113 times the total TB prevalence in Qazvin province in the same year. From 7 diagnosed and treated patients, 4 were cured with the category 1 standard regimen, 1 completed treatment and 2 failed to complete treatment. Improvements are needed in TB case recognition of prisoners, especially newcomers.
Zhou, Chengchao; Chu, Jie; Geng, Hong; Wang, Xingzhou; Xu, Lingzhong
Objective A timely initiation of treatment is crucial to better control tuberculosis (TB). The aim of this study is to describe treatment delay among migrant patients with TB and to identify factors associated with treatment delay, so as to provide evidence for strategy development and improvement of TB control among migrants in China. Design A cross-sectional study was conducted in Shandong province of China. A total of 314 confirmed smear positive migrant patients with pulmonary TB were included. Univariate logistic regression was used to analyse the association of variables with treatment delay among migrant patients with TB. A multilogistic regression model was developed to further assess the effect of variables on treatment delay. Results Of 314 migrant patients with TB, 65.6% experienced treatment delay (>1 day). Household income level, diagnosis symptom severity, understanding of whether TB is curable or not and knowledge about the free TB treatment policy are factors significantly associated with treatment delay. Conclusions Economic status and knowledge about TB are key barriers to accessing TB treatment. An integrated policy of carrying out TB-related health education and publicising the free TB treatment policy among migrants is needed. Health insurance schemes for migrants should be modified to make them transferrable and pro-poor. PMID:25534210
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.
Assefa, Dawit; Klinkenberg, Eveline; Yosef, Genet
The 2013 global roadmap for childhood tuberculosis calls for countries to implement contact screening and provide preventive therapy to children younger than 5 years. Therefore, this study designed to evaluate the implementation status of child contact screening and management in the health facilities of Addis Ababa, Ethiopia. Smear positive TB patients living with children attending daily observed treatment at the TB clinic and health care workers providing service were approached to address the study objective. Structured questionnaires were administered to smear positive index cases living with children whether they were requested to bring children age five year and below for TB screening and to health care providers in HIV, TB and child health clinics to assess their knowledge and practice on contact screening and management. Double data entry and analysis was done using EpiData software 3.1. In 27 health centres, 688 smear-positive index tuberculosis patients were approached of whom 203 (29.5%) reported to have children five years and below in their household. A total of 48 (23.6%) index cases had been requested by the health care workers to bring their children for tuberculosis screening and 45 (93.8%) had complied with this request. Of 230 children living with index smear positive tuberculosis patient, 152 (66.1%) were not screened for tuberculosis, 78 (33.9%) children screened, 2 had tuberculosis, 76 screened negative of which 3 (3.8%) received preventive treatment. None of the health care workers indicated to routinely record and report on child contact management. Household child contact screening and preventive intervention was sub-optimal in Addis Ababa. An important opportunity lost to prevent tuberculosis in young children. Training of health care workers, availing simple symptom based screening tool, and proper documentation could improve implementation.
Adhvaryu, Meghna; Vakharia, Bhasker
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
Micheletti, Vania Celina Dezoti; Kritski, Afrânio Lineu; Braga, José Ueleres
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
Bello, A K; Njoku, C H; Njoku, A K
Among communicable diseases, tuberculosis (TB) is the second leading cause of death worldwide, killing nearly 2 million people each year. It is estimated that about one-third of the world population are infected with TB (2 billion people) and about 10% of this figure will progress to disease state. Most cases are in the less-developed countries of the world. Tuberculosis incidence has been on the increase in Africa, mainly as a result of the burden of HIV infection. Definitive diagnosis of tuberculosis remains based on culture for Mycobacterium tuberculosis, but rapid diagnosis of infectious tuberculosis by simple sputum smear for acid fast bacilli remains an important tool, as more rapid molecular techniques are being developed. Treatment with several drugs for 6 months or more can cure more than 95% of patients. Direct observation of treatment, a component of the recommended five-element DOTS strategy, is judged to be the standard of care by most authorities. Currently only a third of cases worldwide are treated using this approach. There may be need to modify the treatment modalities especially with the choice of drugs and duration of therapy when TB infection occurs in special situation like pregnancy, liver disease, renal failure or even in coexistence with HlV/AIDS or the drug resistant state.
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
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.
Tamhane, Ashutosh; Ambe, Girish; Vermund, Sten H; Kohler, Connie L; Karande, Alka; Sathiakumar, Nalini
Purpose: To determine the factors responsible for patient delay and treatment delay in newly diagnosed sputum smear-positive pulmonary tuberculosis (TB) patients. Methods: Study subjects (N = 150) were randomly selected from municipal health centers in Mumbai, India. Duration of symptoms, treatment, and reason for delay were assessed using interviews and medical records. We defined patient delay as presentation to a health care provider (HCP) >20 days of the onset of TB-related symptoms and treatment delay as therapy initiated more than 14 days after the first consultation (for TB-related symptoms) with an HCP. Results: Of the 150 subjects, 29% had patient delays and 81% had treatment delays. In multivariable analysis, patient delay was significantly associated with the self-perception that initial symptoms were due to TB [odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.1–12.6] and perceived inability to pay for care (OR = 2.9, 95% CI = 1.2–7.1). Treatment delay was significantly associated with consulting a non-allopathic provider (OR = 12.3, 95% CI = 1.4–105) and consulting >3 providers (OR = 5.0, 95% CI = 1.4–17.4). Patient interval was half the treatment interval (median days: 15 vs. 31). Women were slightly more likely to experience patient and treatment delays than men. For two-thirds of the patients, another TB patient was a source of TB-related knowledge, while health education material (16%) and television (10%) played a smaller role. Conclusion: Treatment delay, primarily due to diagnosis delay, was a greater problem than patient delay. Expanding public–public and public–private partnerships and regular training sessions for HCPs might decrease treatment delay. Media coverage and cured TB patients as peer advocates may help to reinforce TB-related health education messages. PMID:22973488
Munsiff, Sonal S; Kambili, Chrispin; Ahuja, Shama Desai
Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. Clinical data support intermittent use of rifapentine with isoniazid during the continuation phase of tuberculosis treatment. Patients with culture-positive, noncavitary, pulmonary tuberculosis whose sputum smear is negative for acid-fast bacilli at the end of the 2-month intensive treatment phase are eligible for rifapentine therapy. Rifapentine should not be used in human immunodeficiency virus-infected patients, given their increased risk of developing rifampin resistance with currently recommended dosages. Rifapentine is not currently recommended for children aged <12 years, pregnant or lactating women, or individuals with culture-negative or extrapulmonary tuberculosis. Rifapentine (600 mg) is administered once weekly with isoniazid (900 mg) during the continuation phase of treatment. This combination should only be given under direct observation. As with rifampin, drug-drug interactions are common, and regular patient monitoring is required. Ease of administration makes this regimen attractive both for tuberculosis-control programs and for patients.
Rangaka, Molebogeng X; Cavalcante, Solange C; Marais, Ben J; Thim, Sok; Martinson, Neil A; Swaminathan, Soumya; Chaisson, Richard E
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.
Borgdorff, Martien W.; Floyd, Katherine; Broekmans, Jaap F.
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
Mitnick, Carole D.; Appleton, Sasha C.; Shin, Sonya S.
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
Neyaz, Md. Kausar; Das, Shilpi
Tuberculosis, commonly known as TB, is the second most fatal infectious disease after AIDS, caused by bacterium called Mycobacterium tuberculosis. Prolonged treatment, high pill burden, low compliance, and stiff administration schedules are factors that are responsible for emergence of MDR and XDR cases of tuberculosis. Till date, only BCG vaccine is available which is ineffective against adult pulmonary TB, which is the most common form of disease. Various unique antibodies have been developed to overcome drug resistance, reduce the treatment regimen, and elevate the compliance to treatment. Therefore, we need an effective and robust system to subdue technological drawbacks and improve the effectiveness of therapeutic drugs which still remains a major challenge for pharmaceutical technology. Nanoparticle-based ideology has shown convincing treatment and promising outcomes for chronic infectious diseases. Different types of nanocarriers have been evaluated as promising drug delivery systems for various administration routes. Controlled and sustained release of drugs is one of the advantages of nanoparticle-based antituberculosis drugs over free drug. It also reduces the dosage frequency and resolves the difficulty of low poor compliance. This paper reviews various nanotechnology-based therapies which can be used for the treatment of TB. PMID:28210505
Casals, M.; Caminero, J. A.; García-García, J. M.; Jiménez-Fuentes, M. A.; Medina, J. F.; Millet, J. P.; Ruiz-Manzano, J.; Caylá, J.
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
Xia, YinYin; Goel, Sonu; Harries, Anthony D.; Zhang, ZhiGuo; Gao, TieJie; Wang, LiXia; Cheng, ShiMing; Lin, Yan; Du, Xin
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
Kim, Lindsay; Moonan, Patrick K.; Heilig, Charles M.; Yelk Woodruff, Rachel S.; Kammerer, J. Steve; Haddad, Maryam B.
SUMMARY Setting Even in persons with complete treatment of their first tuberculosis (TB) episode, patients with a TB history are at higher risk for having TB. Objective Describe factors from the initial TB episode associated with recurrent TB among patients who completed treatment and remained free of TB for at least 12 months. Design US TB cases, stratified by birth origin, during 1993–2006 were examined. Cox proportional hazards regression was employed to assess the association of factors during the initial episode with recurrence at least 12 months after treatment completion. Results Among 632 US-born patients, TB recurrence was associated with age 25–44 (adjusted hazard ratio [aHR] 1.77, 99% confidence interval [CI] 1.02–3.09, attributable fraction [AF] 1%–34%), substance use (aHR 1.57, 99%CI 1.23–2.02, AF 8%–22%), and treatment supervised by health departments (aHR 1.42, 99%CI 1.03–1.97, AF 2%–28%). Among 211 foreign-born patients, recurrence was associated with HIV infection (aHR 2.24, 99%CI 1.27–3.98, AF 2%–9%) and smear-positive TB (aHR 1.56, 99%CI 1.06–2.30, AF 3%–33%). Conclusion Factors associated with recurrence differed by birth origin and might be useful for anticipating greater risk for recurrent TB among certain patients with a TB history. PMID:26688528
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.
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
Ohkado, Akihiro; Matsumoto, Kenji; Komukai, Jun; Yoshida, Hideki; Ishikawa, Nobukatsu
Osaka City has the highest tuberculosis (TB) notification rates in Japan. In the period 1999–2003, the TB control programme was strengthened, and the Stop TB Strategy was implemented to reduce the number of notified cases. The objective of this study was to assess the effect of these control activities in Osaka City, including the implementation of directly observed treatment (DOT), by analysing TB surveillance and routinely collected data. We reviewed the surveillance data of all sputum smear-positive pulmonary tuberculosis (PTB) cases registered in the Osaka City Public Health Office from 2001 to 2008 and data collected from the routine TB programme. The DOT implementation rate increased from 0% in 2001 to 68% in 2008 for smear-positive PTB cases of the general public and to 61% for all PTB cases of the homeless. The proportion of smear-positive PTB cases that had treatment failure and default combined, declined from 8.0% (52 of 650) in 2001 to 3.6% (20 of 548) in 2006. The proportion of cases among the homeless with previous treatment declined from 28% in 2001 to 15% in 2008. The proportion of cases with multidrug resistant-TB (MDR-TB) among those without previous treatment declined from 1.7% in 2001 to 0.9% in 2008. It is logical that reduction in the failure and default rate would lead to the reduction of cases with previous treatment and TB transmission, including resistant TB, therefore to the reduction of MDR-TB rates. PMID:23908949
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
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.
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
Renoux, E; Matan, A Barreh; Sevre, J P; Mohamed Ali, I; Chami, D; Vincent, V
Based on analysis of data collected from the national tuberculosis prevention program in Djibouti between 1990 and 1996, the authors analyzed the relationship between HIV infection and tuberculosis. The study cohort comprised a total of 22,000 patients including 14,000 with documented HIV infection. Although HIV infection probably worsened the situation, it was neither the only nor the main factor involved in the resurgence of tuberculosis. Demographic growth, higher population density, and increasing poverty as well as the quality of the national tuberculosis prevention program must be taken into account. The incidence of smear-negative tuberculosis was not significantly higher in HIV-infected patients (incidence of smear positive cases, > 92%). Extrapulmonary tuberculosis especially of pleural involvement was more common (15% versus 9.4%). Treatment was effective in HIV-infected patients. If directly observed (DOT) therapy was used, there was no risk of emergence of multidrug-resistant tuberculosis strains. Drug side-effects associated with the protocols used in Djibouti were not greater in HIV-infected patients. Most additional mortality observed in HIV-infected tuberculosis patients (10.5% versus 2%) was due to progression of HIV infection.
Chigutsa, Emmanuel; Patel, Kashyap; Denti, Paolo; Visser, Marianne; Maartens, Gary; Kirkpatrick, Carl M J; McIlleron, Helen; Karlsson, Mats O
Days to positivity in automated liquid mycobacterial culture have been shown to correlate with mycobacterial load and have been proposed as a useful biomarker for treatment responses in tuberculosis. However, there is currently no quantitative method or model to analyze the change in days to positivity with time on treatment. The objectives of this study were to describe the decline in numbers of mycobacteria in sputum collected once weekly for 8 weeks from patients on treatment for tuberculosis using days to positivity in liquid culture. One hundred forty-four patients with smear-positive pulmonary tuberculosis were recruited from a tuberculosis clinic in Cape Town, South Africa. A nonlinear mixed-effects repeated-time-to-event modeling approach was used to analyze the time-to-positivity data. A biexponential model described the decline in the estimated number of bacteria in patients' sputum samples, while a logistic model with a lag time described the growth of the bacteria in liquid culture. At baseline, the estimated number of rapidly killed bacteria is typically 41 times higher than that of those that are killed slowly. The time to kill half of the rapidly killed bacteria was about 1.8 days, while it was 39 days for slowly killed bacteria. Patients with lung cavitation had higher bacterial loads than patients without lung cavitation. The model successfully described the increase in days to positivity as treatment progressed, differentiating between bacteria that are killed rapidly and those that are killed slowly. Our model can be used to analyze similar data from studies testing new drug regimens.
Wang, Qi; Hu, Yong Liang; Zhu, Baoli; Woo, Patrick C. Y.
Background Information on treatment outcomes among hospitalized patients with multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are scarce in China. Methodology/Principal Findings We conducted this retrospective study to analyze the characteristics and treatment outcomes in MDR- and XDR-TB patients in the 309 Hospital in Beijing, China during 1996–2009. Socio-demographic and clinical data were retrieved from medical records and analyzed. Logistic regression analysis was performed to identify risk factors associated with poor treatment outcomes and Cox proportional hazards regression model was further used to determine risk factors associated with death in TB patients. Among the 3,551 non-repetitive hospitalized TB patients who had drug susceptibility testing (DST) results, 716 (20.2%) had MDR-TB and 51 (1.4%) had XDR-TB. A total of 3,270 patients who had medical records available were used for further analyses. Treatment success rates (cured and treatment completed) were 90.9%, 53.4% and 29.2% for patients with non-MDR-TB, patients with MDR-TB excluding XDR-TB and patients with XDR-TB, respectively. Independent risk factors associated with poor treatment outcomes in MDR-TB patients included being a migrant (adjusted OR = 1.77), smear-positivity at treatment onset (adjusted OR = 1.94) and not receiving 3 or more potentially effective drugs (adjusted OR = 3.87). Independent risk factors associated with poor treatment outcomes in XDR-TB patients were smear-positivity at treatment onset (adjusted OR = 10.42) and not receiving 3 or more potentially effective drugs (adjusted OR = 14.90). The independent risk factors associated with death in TB patients were having chronic obstructive pulmonary disease (adjusted HR = 5.25) and having hypertension (adjusted HR = 4.31). Conclusions/Significance While overall satisfactory treatment success for non-MDR-TB patients was achieved, more intensive efforts
Lau, Angela; Barrie, James; Winter, Christopher; Elamy, Abdel-Halim; Tyrrell, Gregory; Long, Richard
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
Tsai, Kuo-Sheng; Chang, Hsiao-Ling; Chien, Shun-Tien; Chen, Kwo-Liang; Chen, Kou-Huang; Mai, Ming-Hsin; Chen, Kow-Tong
Despite the existence of a government-run tuberculosis (TB) control program, the current nationwide burden of TB continues to be a public health problem in Taiwan. Intense current and previous efforts into diagnostic, therapeutic, and preventive interventions have focused on TB in adults, but childhood TB has been relatively neglected. Children are particularly vulnerable to severe disease and death following infection, and children with latent infections become reservoirs for future transmission following disease reactivation in adulthood, thus fueling future epidemics. Additional research, understanding, and prevention of childhood TB are urgently needed. This review assesses the epidemiology, diagnosis, treatment, and relevant principles of TB vaccine development and presents efficacy data for the currently licensed vaccines.
Caminero, José A; Cayla, Joan A; García-García, José-María; García-Pérez, Francisco J; Palacios, Juan J; Ruiz-Manzano, Juan
In the last 2 decades, drug-resistant tuberculosis has become a threat and a challenge to worldwide public health. The diagnosis and treatment of these forms of tuberculosis are much more complex and prognosis clearly worsens as the resistance pattern intensifies. Nevertheless, it is important to remember that with the appropriatesystematic clinical management, most of these patients can be cured. These guidelines itemize the basis for the diagnosis and treatment of all tuberculosis patients, from those infected by strains that are sensitive to all drugs, to those who are extensively drug-resistant. Specific recommendations are given forall cases. The current and future role of new molecular methods for detecting resistance, shorter multi-drug-resistant tuberculosis regimens, and new drugs with activity against Mycobacterium tuberculosis are also addressed.
Dalton, James P.; Uy, Benedict; Phummarin, Narisa; Copp, Brent R.; Denny, William A.; Swift, Simon
Much is known regarding the antibiotic susceptibility of planktonic cultures of Mycobacterium tuberculosis, the bacterium responsible for the lung disease tuberculosis (TB). As planktonically-grown M. tuberculosis are unlikely to be entirely representative of the bacterium during infection, we set out to determine how effective a range of anti-mycobacterial treatments were against M. tuberculosis growing as a biofilm, a bacterial phenotype known to be more resistant to antibiotic treatment. Light levels from bioluminescently-labelled M. tuberculosis H37Rv (strain BSG001) were used as a surrogate for bacterial viability, and were monitored before and after one week of treatment. After treatment, biofilms were disrupted, washed and inoculated into fresh broth and plated onto solid media to rescue any surviving bacteria. We found that in this phenotypic state M. tuberculosis was resistant to the majority of the compounds tested. Minimum inhibitory concentrations (MICs) increased by 20-fold to greater than 1,000-fold, underlying the potential of this phenotype to cause significant problems during treatment. PMID:27904808
van Helden, Paul D.; Wilson, Douglas; Colijn, Caroline; McLaughlin, Megan M.; Abubakar, Ibrahim; Warren, Robin M.
Summary: Numerous studies have reported that individuals can simultaneously harbor multiple distinct strains of Mycobacterium tuberculosis. To date, there has been limited discussion of the consequences for the individual or the epidemiological importance of mixed infections. Here, we review studies that documented mixed infections, highlight challenges associated with the detection of mixed infections, and discuss possible implications of mixed infections for the diagnosis and treatment of patients and for the community impact of tuberculosis control strategies. We conclude by highlighting questions that should be resolved in order to improve our understanding of the importance of mixed-strain M. tuberculosis infections. PMID:23034327
Santos, Josemir Belo dos; Figueiredo, Ana Roberta; Ferraz, Cláudia Elise; Oliveira, Márcia Helena de; Silva, Perla Gomes da; Medeiros, Vanessa Lucília Sileira de
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.
Lessells, Richard J.; Swaminathan, Soumya; Godfrey-Faussett, Peter
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
Perronne, C; de Truchis, P
The recent augmentation of the prevalence of multidrug resistant (MDR) tuberculosis is related to the high incidence of tuberculosis in HIV infected people, especially in those with low social status and no medical care; several nosocomial epidemics of MDR tuberculosis were observed in American and European institutions where HIV-infected persons were hospitalized; these MDR tuberculosis were associated with a high mortality-rate and frequent nosocomial transmission to immunocompromised contacts and care workers. The rapid institution of an adequate treatment with ancient antituberculosis agents (cycloserin, capreomycin, aminoglycosides) and/or new drugs (rifabutine, ofloxacin, sparfloxacin, etc) is necessary to avoid mortality and to diminish transmission. Prevention of MDR tuberculosis transmission is very important: patient isolation, adequate and prolonged therapy, better detection of resistance with gene-amplification methods (PCR) which are under investigation.
d’Arc Lyra Batista, Joanna; de Fátima Pessoa Militão de Albuquerque, Maria; de Alencar Ximenes, Ricardo Arraes; Rodrigues, Laura Cunha
Background Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking. Methods A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001–2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up. Results Smoking (OR 2.53, 95% CI 1.23–5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46–8.93) were found to be independently associated with relapse of tuberculosis. Conclusions Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. PMID:18556729
Silva, Diego S; Dawson, Angus; Upshur, Ross E G
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.
Background The adherence to long tuberculosis (TB) treatment is a key factor in TB control programs. Always some patients abandon the treatment or die. The objective of this study is to identify factors associated with defaulting from or dying during antituberculosis treatment. Methods Prospective study of a large cohort of TB cases diagnosed during 2006-2007 by 61 members of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Predictive factors of completion outcome (cured plus completed treatment vs. defaulters plus lost to follow-up) and fatality (died vs. the rest of patients) were based on logistic regression, calculating odds ratios (OR) and 95% confidence intervals (CI). Results Of the 1490 patients included, 29.7% were foreign-born. The treatment outcomes were: cured 792 (53.2%), completed treatment 540 (36.2%), failure 2 (0.1%), transfer-out 33 (2.2%), default 27 (1.8%), death 27 (1.8%), lost to follow-up 65 (4.4%), other 4 (0.3%). Completion outcome reached 93.5% and poor adherence was associated with: being an immigrant (OR = 2.03; CI:1.06-3.88), living alone (OR = 2.35; CI:1.05-5.26), residents of confined institutions (OR = 4.79; CI:1.74-13.14), previous treatment (OR = 2.93; CI:1.44-5.98), being an injecting drug user (IDU) (OR = 9.51; CI:2.70-33.47) and treatment comprehension difficulties (OR = 2.93; CI:1.44-5.98). Case fatality was 1.8% and it was associated with the following variables: age 50 or over (OR = 10.88; CI:1.12-105.01), retired (OR = 12.26;CI:1.74-86.04), HIV-infected (OR = 9.93; CI:1.48-66.34), comprehension difficulties (OR = 4.07; CI:1.24-13.29), IDU (OR = 23.59; CI:2.46-225.99) and Directly Observed Therapy (DOT) (OR = 3.54; CI:1.07-11.77). Conclusion Immigrants, those living alone, residents of confined institutions, patients treated previously, those with treatment comprehension difficulties, and IDU patients have poor adherence and should be targeted for DOT. To reduce fatality rates, stricter monitoring is required
Mirlohi, Maryam-Sadat; Ekrami, Alireza; Shirali, Saeed; Ghobeishavi, Mehdi; Pourmotahari, Fatemeh
Introduction Tuberculosis (TB) is a major global health problem, and anti-tuberculosis drugs can cause severe adverse reactions. The aim of this study was to determine hematological and biochemical changes and associated risk factors in smear positive pulmonary tuberculosis patients undergoing treatment with standard protocols. Methods In a descriptive study, a total of 40 tuberculosis patients aged between 15–60 years were collected from hospitals in Khuzestan Province (Iran) from March 2013 to March 2014. The patients were treated with drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) during the initial two months, followed by isoniazid and rifampicin for the next four to six months. Activities of liver enzymes (ALT, AST, and ALP) and hematological parameters were recorded before and after treatment. Data were analyzed using paired samples t-test and Wilcoxon test by SPSS 16. Results After using drug treatments, hematological parameters (RBC, Hb, HCT, MCV, MCH, and MCHC), except platelet count, were changed significantly (p ≤ 0.001). Liver enzyme activities (ALT, AST, and ALP) were decreased significantly (p ≤ 0.001) after treatment. Conclusion In this study, changes of hematological and biochemical parameters have been observed in patients with pulmonary tuberculosis. It can be concluded that the anti-tuberculosis treatment is associated with changes of hematological parameters and liver enzymes. PMID:27790357
Jacobson, Karen R
This issue provides a clinical overview of tuberculosis, focusing on screening, prevention, diagnosis, and treatment. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
Bonnet, Maryline; Baudin, Elisabeth; Jani, Ilesh V.; Nunes, Elizabete; Verhoustraten, François; Calmy, Alexandra; Bastos, Rui; Bhatt, Nilesh B.; Michon, Christophe
Objectives and Design We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) occurring within 12 weeks of starting antiretroviral therapy, and to evaluate its association with patient outcome at 48 weeks. Methods HIV-tuberculosis co-infected and antiretroviral therapy-naïve adults with less than 250 CD4/mm3 were randomized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment, and were then followed for 48 weeks. Tuberculosis cases were diagnosed using WHO guidelines, and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS. Results The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm3 and HIV-1 RNA of 5.6 log10 copies/mL. Mortality at week 48 was 6.1% (35/573). Fifty-three (9.2%) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy. Being female and having a low CD4 count, high HIV-1 RNA load, low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS. After adjustment for baseline body mass index, CD4 count and hemoglobin, occurrence of tuberculosis-IRIS was independently associated with 48-week mortality (aOR 2.72 95%CI 1.14-6.54). Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS. Conclusion In this large prospective cohort, tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation. PMID:24367678
Reynolds, Jonathan; Heysell, Scott K
Introduction Tuberculosis (TB) remains the leading cause of death from a curable infectious disease; drug-resistant TB threatens to dismantle all prior gains in global control. Suboptimal circulating anti-TB drug concentrations can lead to lack of cure and acquired drug resistance. Areas covered This review will introduce pharmacokinetic parameters for key anti-TB drugs, as well as the indications and limitations of measuring these parameters in clinical practice. Current and novel methodologies for delivering anti-TB pharmacokinetic-pharmacodynamic data are highlighted and gaps in operational research described. Expert opinion Individual pharmacokinetic variability is commonplace, underappreciated and difficult to predict without therapeutic drug monitoring (TDM). Pharmacokinetic thresholds associated with poor TB treatment outcome in drug-susceptible TB have recently been described and may now guide the application of TDM, but require validation in a variety of settings and comorbidities. Dried blood spots for TDM and prepackaged multidrug plates for minimum inhibitory concentration testing will overcome barriers of accessibility and represent areas for innovation. Operationalizing pharmacokinetics has the potential to improve TB outcomes in the most difficult-to-treat forms of the disease such as multidrug resistance. Clinical studies in these areas are eagerly anticipated and we expect will better define the rational introduction of novel therapeutics. PMID:24597717
Belizario, V; Guan, M; Borja, L; Ortega, A; Leonardia, W
The clinical epidemiology of pulmonary paragonimiasis and tuberculosis was investigated in a known endemic municipality of Sorsogon, Philippines. Records of diagnosed tuberculosis patients on treatment and follow up at the local Rural Health Unit over a two year period from 1993 to 1994 were reviewed to provide an overview of pulmonary tuberculosis in the area, specifically to describe the population at risk, the basis for diagnosis and the proportion of case notification who were sputum negative. Patients from the same group of individuals as well as undiagnosed tuberculosis patients with productive cough, fever with chest and/or back pain, or hemoptysis were examined to look into clinical manifestations, duration of symptoms, history of crab-eating and sputum examination results for acid-fast bacilli and Paragonimus. There was difficulty in determining the number of non-responders as the records did not have any provision for the recording of such. Annual tuberculosis case notification rates for the two years (374 and 401 per 100,000 population) were higher than the national figure in 1991 (325 per 100,000 population) indicating that tuberculosis is still a major health problem in the area and tuberculosis control efforts may have to be more aggressive to better contain the disease. Twenty-six out of 160 individuals surveyed were sputum smear positive for Paragonimus. Paragonimiasis rates were not significantly different in the two groups (15.6% vs 16.9%, respectively) indicating that there is a need for routine sputum examination for Paragonimus which is not available at present. Only six patients surveyed were sputum smear positive for acid-fast bacilli. A high index of suspicion is necessary to diagnose paragonimiasis and to be able to differentiate it from tuberculosis. The diagnosis may be suggested by a patient's place of origin being a known endemic area, a long period of chronic cough and the habit of eating raw or insufficiently cooked crabs or crayfish
Lv, Xiaozhen; Tang, Shaowen; Xia, Yinyin; Wang, Xiaomeng; Yuan, Yanli; Hu, Daiyu; Liu, Feiying; Wu, Shanshan; Zhang, Yuan; Yang, Zhirong; Tu, Dehua; Chen, Yixin; Deng, Peiyuan; Ma, Yu; Chen, Ru; Zhan, Siyan
Background More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China. Methods A prospective population-based cohort study was performed during 2007–2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration. Results A total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44–2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43–4.68). Conclusions The incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely. PMID:23750225
Ausina, V; Gamboa, F; Gazapo, E; Manterola, J M; Lonca, J; Matas, L; Manzano, J R; Rodrigo, C; Cardona, P J; Padilla, E
Five hundred twenty processed respiratory specimens from 326 patients received for the diagnosis of tuberculosis or other mycobacterial infections were tested by means of the LCx Mycobacterium tuberculosis Assay from Abbott Laboratories, which uses ligase chain reaction technology for the direct detection of M. tuberculosis complex in respiratory specimens. The results of the LCx M. tuberculosis Assay were compared with the results of culture and staining techniques. After a combination of culture results and the patient's clinical data, a total of 195 specimens were collected from 110 patients who were positively diagnosed as having pulmonary tuberculosis. Twenty-three of these 195 specimens which corresponded to 10 patients with a history of pulmonary tuberculosis (TB) and anti-TB treatment ranging from 1 to 6 months were culture negative. The other 172 specimens were culture positive for M. tuberculosis. With an overall positivity rate of 37.5% (195 of 520 specimens), the sensitivity, specificity, and positive and negative predictive values were 90.8, 100, 100, and 94.7%, respectively, for the LCx M. tuberculosis Assay; 88.2, 100, 100, and 93.4%, respectively, for culture; and 82.6, 92, 72.9, and 97.6%, respectively, for acid-fast staining. For 161 specimens (82.6%) from patients smear positive for the disease and 34 specimens (17.4%) from patients smear negative for the disease, the sensitivity values for the LCx M. tuberculosis Assay were 98.8 and 53%, respectively. There were no statistically significant differences in the sensitivities and specificities between the LCx M. tuberculosis Assay and culture (P > 0.05). Conclusively, the LCx M. tuberculosis Assay has proved to have an acceptable sensitivity and a high specificity in detecting M. tuberculosis and has the potential of reducing the diagnosis time to an 8-h working day. PMID:9230369
... Loss Surgery? A Week of Healthy Breakfasts Shyness Tuberculosis KidsHealth > For Teens > Tuberculosis A A A What's in this article? TB ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...
... Loss Surgery? A Week of Healthy Breakfasts Shyness Tuberculosis KidsHealth > For Teens > Tuberculosis Print A A A What's in this article? ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...
Mvé, Médard Toung; Bisvigou, Ulrich; Barry, Ndeye Coura Diop; Ondo, Clément Ella; Nkoghe, Dieudonné
Tuberculosis is an important public health problem in Gabon, and the DOTS strategy recommended by the World Health Organisation has not been successfully applied. In 2006, 45% of patients abandoned treatment during the first phase. A pilot cross-sectional study was thus conducted from September 1 to November 30, 2006, at the Nkembo Tuberculosis Centre in Libreville, Gabon. Thirty patients with positive microscopy results who returned after having interrupted treatment completed a standardised questionnaire. They were mainly young men: their mean age was 33 years old and the male/female ratio was 2.7. Reasons for having abandoned treatment were a lack of money to pay for it (43%) and an impression that they had been cured (23%). The motivations for resuming treatment were the return of symptoms (73%). The risk of drug resistance requires that the Gabonese government play a greater role in the fight against tuberculosis.
Mercer, T.; Kimani, S.; Braitstein, P.; Buziba, N.; Carter, E. J.
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
The second in this two part unit on tuberculosis examines diagnosis and treatment options. Part I outlined background on epidemiology and control of this disease. This part draws on the guidance set out by the National Institute for Health and Clinical Excellence. Diagnostic methods are discussed and the standard treatment regimen is outlined.
Mahato, Roshan Kumar; Vaeteewootacharn, Kriangsak; Koju, Rajendra; Bhattarai, Ratna
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
Abidi, Maheen Z; Haque, Javeria; Varma, Parvathi; Olteanu, Horatiu; Guru Murthy, Guru Subramanian; Dhakal, Binod; Hari, Parameswaran
Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib.
Haque, Javeria; Varma, Parvathi; Guru Murthy, Guru Subramanian; Dhakal, Binod; Hari, Parameswaran
Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib. PMID:27843657
Lanoix, Jean-Philippe; Chaisson, Richard E; Nuermberger, Eric L
The disappointing recent failure of fluoroquinolone-containing regimens to shorten the duration of tuberculosis treatment in costly phase 3 trials has raised serious questions about the reliability of preclinical tuberculosis models, especially mice, and the current paradigm of regimen development. Therefore we re-examined data from murine models and early-stage clinical trials on which the pivotal trials were based, concluding that phase 3 trial results were in line with preceding studies. Finally, we offer suggestions for a more efficient and integrated preclinical and clinical regimen development program where quantitative pharmacokinetic and pharmacodynamic models more predictive of curative treatment durations are set forth.
Aleksandrova, E A; Lepilin, A V; Kazimirova, N E; Shul'diakov, A A
For the purpose to determine the clinic-pathogenetic efficacy of Cycloferon liniment in the combined therapy of parodontitis of patients with focal tuberculosis medical examination and treatment of 40 patients is carried out. It is established, that use of liniment Cycloferon in the combined treatment of patients with focal tuberculosis allows to accelerate process of normalization of lipid peroxidation parameters and antioxidant potential of blood, to decrease infection load (Herpes symplex virus I, Candida albicans, Staphylococcus aureus) in parodontal recess and evidence of local inflammation with reduction of activity of the tumours necrosis factor and interleukin 1beta, that provides acceleration of recuperation processes, lowering the frequency of parodontitis relapses.
Shargie, Estifanos Biru; Mørkve, Odd; Lindtjørn, Bernt
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
Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; ...
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
Nhung, Nguyen Viet; Hoa, Nguyen Binh; Khanh, Pham Huyen; Hennig, Cornelia
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.
Dorji, T.; Edgnton, M. E.; Kumar, A. M. V.; Wangchuk, D.; Dophu, U.; Jamtsho, T.; Rinzin, C.
Setting: All hospitals and health centres under the National Tuberculosis Control Programme (NTCP) in Bhutan. Objective: To describe the number and proportion of childhood tuberculosis (TB) cases registered under the NTCP in 2010, their demographic and clinical characteristics and any associations with treatment outcomes. Design: Retrospective cohort study involving a review of TB treatment cards and registers. Results: Of 1332 TB cases registered, 187 (14%) were children aged <15 years, 75 (40%) were aged <5 years, and 180 (96%) were new cases; nearly half were extra-pulmonary TB, with lymphadenitis being the most common form. The overall treatment success rate was 93%, and none of the demographic and clinical characteristics were associated with treatment outcomes. A few recording deficiencies were identified. Conclusion: TB in children is well recognised in Bhutan, and their treatment outcomes were excellent. PMID:26392988
Harries, A. D.; Maher, D.; Nunn, P.
The overlap between the populations in sub-Saharan Africa infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis has led to an upsurge in tuberculosis cases over the last 10 years. The relative increase in the proportion of notified sputum-smear-negative pulmonary tuberculosis (PTB) cases is greater than that of sputum-smear-positive PTB cases. This is a consequence of the following: the association between decreased host immunity and reduced sputum smear positivity; the difficulty in excluding other HIV-related diseases when making the diagnosis of smear-negative PTB; and an increase in false-negative sputum smears because of overstretched resources. This article examines problems in the diagnosis and treatment of smear-negative PTB in high-HIV-prevalence areas in sub-Saharan Africa. The main issues in diagnosis include: the criteria used to diagnose smear-negative PTB; the degree to which clinicians actually follow these criteria in practice; and the problem of how to exclude other respiratory diseases that can resemble, and be misdiagnosed as, smear-negative PTB. The most important aspect of the treatment of smear-negative PTB patients is abandoning 12-month "standard" treatment regimens in favour of short-course chemotherapy. Operational research is necessary to determine the most cost-effective approaches to the diagnosis and treatment of smear-negative PTB. Nevertheless, substantial improvement could be obtained by implementing the effective measures already available, such as improved adherence to diagnostic and treatment guidelines. PMID:10191561
Rutherford, Merrin; Alisjahbana, Bachti; Maharani, Winni; Sampurno, Hedy; van Crevel, Reinout; Hill, Philip C.
Background As part of a formal evaluation of the Quantiferon-Gold in-tube assay (QFT-IT) for latent TB infection we compared its sensitivity to the tuberculin skin test (TST) in confirmed adult TB cases in Indonesia. Smear-positive TB disease was used as a proxy gold standard for latent TB infection. Methods and Findings We compared the sensitivity of QFT-IT and TST in 98 sputum smear and chest x-ray positive TB cases and investigated risk factors for negative and discordant results in both tests. Both tests showed high sensitivity; (QFT-IT; 88.7%: TST; 94.9%), not significantly different from each other (p value 0.11). Very high sensitivity was seen when tests were combined (98.9%). There were no variables significantly associated with discordant results or with a negative TST. For QFT-IT which particular staff member collected blood was significantly associated with test positivity (p value 0.01). Study limitations include small sample size and lack of culture confirmation or HIV test results. Conclusions The QFT-IT has similar sensitivity in Indonesian TB cases as in other locations. However, QFT-IT, like the TST cannot distinguish active TB disease from LTBI. In countries such as Indonesia, with high background rates of LTBI, test specificity for TB disease will likely be low. While our study was not designed to evaluate the QFT-IT in the diagnosis of active TB disease in TB suspects, the data suggest that a combination of TST and QFT-IT may prove useful for ruling out TB disease. Further research is required to explore the clinical role of QFT-IT in combination with other TB diagnostic tests. PMID:20711257
Mir Viladrich, Isabel; Daudén Tello, Esteban; Solano-López, Guillermo; López Longo, Francisco Javier; Taxonera Samso, Carlos; Sánchez Martínez, Paquita; Martínez Lacasa, Xavier; García Gasalla, Mercedes; Dorca Sargatal, Jordi; Arias-Guillén, Miguel; García García, José Maria
Tuberculosis risk is increased in patients with chronic inflammatory diseases receiving any immunosuppressive treatment, notably tumor necrosis factor (TNF) antagonists therapy. Screening for the presence of latent infection with Mycobacterium tuberculosis and targeted preventive treatment to reduce the risk of progression to TB is mandatory in these patients. This Consensus Document summarizes the current knowledge and expert opinion of biologic therapies including TNF-blocking treatments. It provides recommendations for the use of interferon-gamma release assays (IGRA) and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in these patients, and for the type and duration of preventive therapy.
Sharma, Surendra K.; Mohan, Alladi; Sharma, Abhishek
Miliary tuberculosis (TB) is a potentially lethal disease if not diagnosed and treated early. Diagnosing miliary TB can be a challenge that can perplex even the most experienced clinicians. Clinical manifestations are nonspecific, typical chest radiograph findings may not be evident till late in the disease, high resolution computed tomography (HRCT) shows randomly distributed miliary nodules and is relatively more sensitive. Ultrasonography, CT and magnetic resonance imaging (MRI) are useful in discerning the extent of organ involvement by lesions of miliary TB in extra-pulmonary locations. Fundus examination for choroid tubercles, histopathological examination of tissue biopsy specimens, conventional and rapid culture methods for isolation of Mycobacterium tuberculosis, drug-susceptibility testing, along with use of molecular biology tools in sputum, body fluids, other body tissues are useful in confirming the diagnosis. Although several prognostic markers have been described which predict mortality, yet untreated miliary TB has a fatal outcome within one year. A high index of clinical suspicion and early diagnosis and timely institution of anti-tuberculosis treatment can be life-saving. Response to first-line anti-tuberculosis drugs is good but drug-induced hepatotoxicity and drug-drug interactions in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients pose significant problems during treatment. However, sparse data are available from randomized controlled trials to define the optimum regimen and duration of treatment in patients with drug-sensitive as well as drug-resistant miliary TB, including those with HIV/AIDS. PMID:22771605
Kolappan, C.; Subramani, R.; Karunakaran, K.; Narayanan, P. R.
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
Villegas, Leonela; Huaman, Moises A.; Van der Stuyft, Patrick; Gotuzzo, Eduardo; Seas, Carlos
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
Chen, Guo; He, Jian-Qing
Abstract Rationale: Disseminated intravascular coagulation (DIC) induced by daily rifampicin therapy is rare, especially the patient is absent of malignancy, severe infection, and prior exposure to rifampicin. Patient concerns: We report a case of DIC induced by daily rifampicin treatment for pulmonary tuberculosis. A 22-year-old, previously healthy man received an anti-tuberculosis therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide on the daily dose recommended by the World Health Organization tuberculosis guidelines after a diagnosis of pulmonary tuberculosis. Two weeks later, he was transferred to the West China Hospital with nasal hemorrhage for 1 week, hematochezia, hematuria, and petechiae for 5 days. Diagnoses: Laboratory data and symptoms on admission indicated DIC. Interventions: The anti-tuberculosis drugs were discontinued after admission and he was initiated with targeted treatment for DIC, omeprazole and polyene hosphatidylcholine infusion, as well as nutrition supportive treatment. Five days after admission, ethambutol, moxifloxacin, and amikacin were added to the patient without further active hemorrhage. Eight days after admission, the platelet count had risen gradually. Isoniazid was administered on 24 days after admission, while his liver function tests and platelet counts returned to normal. No recurrence of DIC occurred. The diagnosis of rifampicin-induced DIC was confirmed. Outcomes: The patient recovered and left hospital with isoniazid, ethambutol, levofloxacin, and streptomycin after 4 weeks of hospitalization. There was no recurrence of DIC or hemorrhage during the 8 months of follow-up. The literature review revealed that there were 10 other cases of rifampicin-induced DIC. Only 4 cases received rifampicin on a daily basis for pulmonary tuberculosis treatment and the others were on intermittent dosing schedule for pulmonary tuberculosis or leprosy treatment. Lessons: As a rare adverse effect, DIC induced by
Corbett, Elizabeth L; Marston, Barbara; Churchyard, Gavin J; De Cock, Kevin M
Rapid scale-up of antiretroviral treatment programmes is happening in Africa, driven by international advocacy and policy directives and supported by unprecedented donor funding and technical assistance. This welcome development offers hope to millions of HIV-infected Africans, among whom tuberculosis is the major cause of serious illness and death. Little in the way of HIV diagnosis or care was previously offered to patients with tuberculosis, by either national tuberculosis or AIDS control programmes, with tuberculosis services focused exclusively on diagnosis and treatment of rising numbers of patients. Tuberculosis control in Africa has yet to adapt to the new climate of antiretroviral availability. Many barriers exist, from drug interactions to historic differences in the way that tuberculosis and HIV are perceived, but failure to successfully integrate HIV and tuberculosis control will threaten the viability of both programmes. Here, we review tuberculosis epidemiology in Africa and policy implications of HIV/AIDS treatment scale-up.
Terra, Maria Fernanda; Bertolozzi, Maria Rita
This is a qualitative study performed in the theoretical framework of the Theory of Social Determination of the Health-Disease process and the concept of Compliance. The goal was to analyze meanings of DOTS in compliance with tuberculosis treatment, according to healthcare professionals of the Technical Healthcare Supervision of Butantã (SUVIS), a region of the São Paulo City Healthcare Secretariat, Brazil. The project was submitted to the Ethics Committee of the São Paulo Municipal Health Secretariat. All professionals (22 people) developing DOTS were interviewed, including service coordinators, healthcare professionals and the DOTS coordinator for the region. The statements were analyzed with an appropriate technique for discourse analysis. The results appoint that the strategy presents more potentialities than limits and is effective regarding compliance, since it allows the professionals to welcome and monitor the patients, considering their needs. The importance of increasing the understanding of compliance is also noted, so that it can go beyond the simple intake of medication, integrating the care for the sick person and his or her necessities by transcending those restricted to the biological dimension.
Ferrer, X; Kirschbaum, A; Toro, J; Jadue, J; Muñoz, M; Espinoza, A
A prospective study was conducted to estimate the current magnitude of adherence to short-course tuberculosis treatment, the degree of abandonment, the characteristics of treatment dropouts, and the causes of this abandonment. The study group was made up of tuberculosis patients over the age of 15 who received care at the Western and Southern Health Services of the Metropolitan Region of Santiago, Chile, between 1 October 1987 and 31 January 1988. The percentage abandoning treatment, calculated by the life table method, was 11.5. The profile of patients who dropped out of treatment was as follows: male, under 45 years of age, single, low level of education, no steady work, homeless, and alcoholic. In addition, an opinion survey on the variables associated with abandonment was conducted and it was concluded that the main ones were alcoholism and intolerance to tuberculosis drugs. Awareness of this profile makes it possible to take measures to prevent patients from abandoning treatment, as well as to educate and even hospitalize at the start of treatment those tuberculous patients exhibiting such a profile.
Mlilo, N; Sandy, C; Harries, A D; Kumar, A M V; Masuka, N; Nyathi, B; Edginton, M; Isaakidis, P; Manzi, M; Siziba, N
Zimbabwe National Tuberculosis Guidelines advise that direct observation of anti-tuberculosis treatment (DOT) can be provided by a family member/relative as a last resort. In 2011, in Nkayi District, of 763 registered tuberculosis (TB) patients, 59 (8%) received health facility-based DOT, 392 (51%) received DOT from a trained community worker and 306 (40%) from a family member/relative. There were no differences in TB treatment outcomes between the three DOT groups, apart from a higher frequency rate of 'no reported outcomes' for those receiving family-based DOT. Family members should be trained to use a suitable DOT support package.
Reddy, K K; Ananthakrishnan, R; Jacob, A G; Das, M; Isaakidis, P; Kumar, A M V
India mainly uses passive case finding to detect tuberculosis (TB) patients through the Revised National Tuberculosis Control Programme (RNTCP). An intensified case finding (ICF) intervention was conducted among vulnerable communities in two districts of Karnataka during July-December 2013; 658 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 8.8% relative to the pre-intervention period (July-December 2012) in intervention communities as compared to an 8.6% decrease in communities without the ICF intervention. ICF activities brought TB services closer to vulnerable communities, moderately increasing TB case detection rates.
Faustini, A; Hall, A J; Perucci, C A
In order to facilitate the control of tuberculosis (TB), the World Health Organization (WHO) has defined a standardised short-course chemotherapy and a strategy, directly observed therapy. In 2000, WHO surveillance of TB treatments in Europe recorded a successful outcome rate of 77%. The aim of this report is to estimate treatment outcomes in European countries based on published studies and to identify their determinants. A systematic review was conducted of published reports of TB treatment outcomes in Europe. Meta-analysis, meta-regression and subgrouping were used to pool treatment outcomes and analyse associations with mean age, sex, immigration status and multidrug resistance. Of the 197 articles identified in the search, 26 were eligible for the review; 74.4% of outcomes were successful, 12.3% were unsuccessful and 6.8% of patients died. Heterogeneity was high for all outcomes. National estimates were possible for six countries. Multidrug resistance was inversely associated with successful outcome, which were fewer in populations with >9% multidrug-resistant TB, and in patients aged <44 yrs. Successful tuberculosis treatment outcomes were below the 85% threshold suggested by the World Health Organization. There was an inverse association with levels of multidrug-resistant tuberculosis. The unexplained heterogeneity between the studies for unsuccessful outcomes seems to be due to differing interpretations given to World Health Organization definitions.
Annual reports of tuberculosis (TB) statistics in Japan have been compiled mainly from the database of the nationwide computerized tuberculosis surveillance system, which has been in operation since 1987. This system has been revised several times. The latest revision was conducted in 2007, and much new information was added. This summary of tuberculosis notification statistics is the first report of a new series for the Tuberculosis Annual Report 2010. The statistics are summarized as follows: The TB notification rate fell below 20 per 100,000 in 2007 and continued to decline, reaching 18.2 in 2010. However, there were still 23,261 TB patients newly notified in 2010. For sputum-smear positive pulmonary TB, the patient count was 9,019, with an incidence rate of 7.0 per 100,000 in 2010. Since June 2007, it has been compulsory to notify patients with latent TB infections (LTBI) requiring treatment; the number notified in 2010 was 4,930.
Padmapriyadarsini, C.; Narendran, G.; Swaminathan, Soumya
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
Funnyé, A. S.; Ganesan, K.; Yoshikawa, T. T.
This study examined the clinical characteristics and outcome of pulmonary tuberculosis in African Americans hospitalized in a teaching hospital in south-central Los Angeles from May 1992 through April 1994. The charts of 41 African Americans with culture-positive Mycobacterium tuberculosis were reviewed. Predisposing factors for pulmonary tuberculosis were identified in nearly half of cases. Cough and fever were the most common symptoms. Seventy-six percent had positive acid-fast bacilli (AFB) smears. Nine patients were human immunodeficiency virus (HIV)-positive, and 6 of 9 HIV-positive patients had positive AFB smears whereas 17 of 19 HIV-negative patients had positive AFB smears. Radiographic changes were not significantly different between HIV-positive and HIV-negative patients. Drug resistance was identified in nine of 31 patients (29%). Eight of 41 patients (19.5%) died, with 2 being drug resistant. Human immunodeficiency virus infection was a major predisposing factor for tuberculosis, and no statistical differences were found in radiographic features or AFB smear positivity between HIV-positive and HIV-negative patients. Drug resistance and mortality were disproportionately high. These results indicate that HIV infection and drug resistance are major problems that predispose for tuberculosis infection and make its treatment difficult. PMID:9510620
Ghali, Iraqi; Kizub, Darya; Billioux, Alexander C.; Bennani, Kenza; Bourkadi, Jamal Eddine; Benmamoun, Abderrahmane; Lahlou, Ouafae; Aouad, Rajae El; Dooley, Kelly E.
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
Achkar, Jacqueline M.; Dong, Yuxin; Holzman, Robert S.; Belisle, John; Kourbeti, Irene S.; Sherpa, Tsering; Condos, Rany; Rom, William N.; Laal, Suman
The 81-kDa malate synthase (MS; Rv 1837c) and the 27-kDa MPT51 (Rv 3803c) of Mycobacterium tuberculosis are immunodominant antigens recognized by serum antibodies from ∼80% of human immunodeficiency virus-negative smear-positive tuberculosis patients from India. We now provide evidence that the use of the MS/MPT51-based serodiagnostic assay can serve as an adjunct to sputum microscopy in the rapid diagnosis of pulmonary tuberculosis. PMID:17090645
Flynn, Michael G; Brown, Lynne K
The proportion of eligible persons identified who are tested for latent tuberculosis (TB), offered treatment, and complete treatment are performance indicators in tuberculosis control. We report a retrospective database review of the Migrant Screening Clinic, Department of Respiratory and Sleep Disorders Medicine at Western Health Footscray Hospital during the years 1996-2006. Of 7,225 migrants aged less than 35 years, tuberculin skin testing (TST) was performed for 3,589 (49.7%), including 2,641 (65.6%) of 4,024 migrants under 35 years with an abnormal chest radiograph, and 2,297 (59.0%) of 3,893 migrants born in a high-burden country. Of 3,589 persons with both chest radiograph and TST results, 1,487 (41.4%) were referred for follow-up, including 81.3% of those with TST ≥10 mm. Outcome data were available for 1,047 persons considered for treatment of latent TB, of whom 12.5% did not attend an initial appointment, 21.6% attended and were not offered treatment, 65.9% attended and were offered treatment, and 41.7% completed treatment for latent TB. The Victorian program for treatment of latent TB in migrants has testing, treatment offer and treatment completions rates similar to other published studies. The impact on TB control is limited by the small proportion of migrants referred to this program.
Bélard, Sabine; Heuvelings, Charlotte C; Janssen, Saskia; Grobusch, Martin P
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.
Dheda, Keertan; Barry, Clifton E; Maartens, Gary
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.
Pothukuchi, Madhavi; Nagaraja, Sharath Burugina; Kelamane, Santosha; Satyanarayana, Srinath; Shashidhar; Babu, Sai; Dewan, Puneet; Wares, Fraser
Background Under India's Revised National Tuberculosis Control Programme (RNTCP), all household contacts of sputum smear positive Pulmonary Tuberculosis (PTB) patients are screened for TB. In the absence of active TB disease, household contacts aged <6 years are eligible for Isoniazid Preventive Therapy (IPT) (5 milligrams/kilogram body weight/day) for 6 months. Objectives To estimate the number of household contacts aged <6 years, of sputum smear positive PTB patients registered for treatment under RNTCP from April to June'2008 in Krishna District, to assess the extent to which they are screened for TB disease and in its absence initiated on IPT. Methods A cross sectional study was conducted. Households of all smear positive PTB cases (n = 848) registered for treatment from April to June'2008 were included. Data on the number of household contacts aged <6 years, the extent to which they were screened for TB disease, and the status of initiation of IPT, was collected. Results Households of 825 (97%) patients were visited, and 172 household contacts aged <6 years were identified. Of them, 116 (67%) were evaluated for TB disease; none were found to be TB diseased and 97 (84%) contacts were initiated on IPT and 19 (16%) contacts were not initiated on IPT due to shortage of INH tablets in peripheral health centers. The reasons for non-evaluation of the remaining eligible children (n = 56, 33%) include no home visit by the health staff in 25 contacts, home visit done but not evaluated in 31 contacts. House-hold contacts in rural areas were less likely to be evaluated and initiated on IPT [risk ratio 6.65 (95% CI; 3.06–14.42)]. Conclusion Contact screening and IPT implementation under routine programmatic conditions is sub-optimal. There is an urgent need to sensitize all concerned programme staff on its importance and establishment of mechanisms for rigorous monitoring. PMID:21799875
Demir, Müge; Örnek Büken, Nüket
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.
Bromberg, Silvio Eduardo; do Amaral, Paulo Gustavo Tenório
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
Kittikraisak, Wanitchaya; Burapat, Channawong; Kaewsa-ard, Samroui; Watthanaamornkiet, Wanpen; Sirinak, Chawin; Sattayawuthipong, Wanchai; Jittimanee, Suksont; Pobkeeree, Vallerut; Varma, Jay K
Ensuring completion of tuberculosis (TB) treatment remains a major public health problem. In HIV-infected patients, TB is the most common severe opportunistic infection. Few studies have evaluated risk factors for TB treatment default in HIV-infected patients. We conducted a prospective, observational study of HIV-infected TB patients in Thailand. Patients underwent standardised evaluations at the beginning of TB treatment, at the end of the intensive phase and at the end of TB treatment. TB treatment outcomes were assessed according to WHO guidelines. The analysis was limited to patients who defaulted or who had treatment success. Of the 554 patients analysed, 61 (11%) defaulted. In multivariate analysis, factors associated with TB treatment default included incarceration history [adjusted odds ratio (AOR) 2.0, 95% CI 1.1-3.7), smoking (AOR 2.3, 95% CI 1.3-4.1) and having a symptom complaint score >15 (AOR 3.4, 95% CI 1.4-8.0); one marker of wealth, namely owning a refrigerator, was protective (AOR 0.4, 95% CI 0.2-0.8). Default during TB treatment was a significant problem in HIV-infected patients. Reducing default may require enhancing services for patients with a history of incarceration or smoking and designing patient-centred systems to address poverty and patient wellness.
Reis-Santos, Barbara; Gomes, Teresa; Horta, Bernardo Lessa; Maciel, Ethel Leonor Noia
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
Behzadifar, Masoud; Mirzaei, Masoud; Behzadifar, Meysam; Keshavarzi, Abouzar; Behzadifar, Maryam; Saran, Maryam
Background: Despite effective diagnosis and treatment, prevalence of tuberculosis (TB) is still growing. The directly observed treatment, short-course (DOTS) strategy to treat TB was introduced by the World Health Organization more than a decade ago. Little is known about patients’ experience of TB treatment, according to DOTS, in Iran. Objectives: This study aimed to understand the patients’ experience of tuberculosis treatment according to DOTS in Iran. Patients and Methods: This study is a qualitative study, using content analysis to examine patients’ experience of TB treatment and to understand their compliance during DOTS. In this study, a semi-structured interview with open questions was answered by 40 patients, who had a diagnosis of pulmonary and extrapulmonary tuberculosis, and improved during the course of their treatment. The method of sampling was purposive sample and the interview process lasted until data saturation. Results: Data analysis resulted in the extraction of six themes, which reflect the experiences of the study participants. The themes are: 1) individual factors; 2) change of the attitudes and beliefs of patients on TB treatment; 3) support terms of patients with tuberculosis; 4) the role of health care professionals; 5) social factors and 6) the financial burden. Conclusions: Successful completion of TB treatment requires an effective partnership between the patient and health care professionals, and a harmony between the cultural context, attitude of the patient, family support and health literacy. Future health policies should address these issues to improve patients’ adherence to DOTS. PMID:26023334
Essential facts Tuberculosis (TB) is an infection caused by a bacterium, mycobacterium tuberculosis. While it can affect any part of the body, only pulmonary TB is infectious. According to the charity TB Alert, there were 5,758 cases of TB in the UK in 2015 and 39% of them were in London. This represented a fall from a peak of 8,919 cases in 2011. Left untreated, TB is life-threatening, but is usually curable with antibiotics. The sooner it is diagnosed and treated, the better, both for the person's health and in preventing them from passing the infection on to others.
Essential facts Tuberculosis (TB) is an infection caused by a bacterium, mycobacterium tuberculosis. While it can affect any part of the body, only pulmonary TB is infectious. According to the charity TB Alert, there were 5,758 cases of TB in the UK in 2015 and 39% of them were in London. This represented a fall from a peak of 8,919 cases in 2011. Left untreated, TB is life-threatening, but is usually curable with antibiotics. The sooner it is diagnosed and treated, the better, both for the person's health and in preventing them from passing the infection on to others.
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
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
Alshahrani, Amer Saeed
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
Thee, S; Garcia-Prats, A J; Donald, P R; Hesseling, A C; Schaaf, H S
The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens as well as in the prevention of drug-resistant TB. The objective of this review was to identify existing evidence for the use of the fluoroquinolones ofloxacin, levofloxacin and moxifloxacin in the treatment of TB in children. Existing data from in vitro, animal and human studies consistently demonstrate the efficacy of the fluoroquinolones against Mycobacterium tuberculosis, with superiority of levofloxacin and moxifloxacin compared to ofloxacin. In vitro and murine studies demonstrated the potential of moxifloxacin to shorten drug-susceptible TB treatment, but in multiple randomized controlled trials shortened fluoroquinolone-containing regimens have not been non-inferior compared to standard therapy. Resistance occurs frequently via mutations in the gyrA gene, and emerges rapidly depending on the fluoroquinolone concentration, with newer more potent fluoroquinolones less likely to develop resistance. Emerging data from paediatric studies underlines the importance of fluoroquinolones in the treatment of MDR-TB in children. There is a paucity of pharmacokinetic data especially in children <5 years of age and HIV-infected children; existing studies show substantially lower serum concentrations in children compared to adults at currently recommended doses, probably due to faster elimination. This has implications for optimizing paediatric treatment and for the development of resistance. Fluoroquinolone use has been restricted in children due to concerns about drug-induced arthropathy. The available data does not demonstrate any serious arthropathy or other severe toxicity in children. Although there is limited paediatric safety data for the prolonged treatment of MDR-TB, extended administration of fluoroquinolones in adults with MDR-TB does not show serious adverse effects and there is no evidence
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
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
Lee, Bai-Yu; Clemens, Daniel L.; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A.
The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis. PMID:28117835
Lee, Bai-Yu; Clemens, Daniel L; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A
The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis.
Holden, Maria Arroyo; Huttlinger, Kathleen; Schultz, Pamela; Mullins, Iris; Forster-Cox, Sue
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.
Caminero Luna, J A
Tuberculosis (TB) remains the most important human infectious disease. Currently, the TB diagnosis is still based on the clinical presentation, radiographic findings and microbiological results; all of which have sensitivity or specificity issues. For that reason, the immediate future involves rapid molecular microbiological techniques, in particular GeneXpert (which is more sensitive than bacilloscopy and is able to detect rifampicin resistance) and GenoType. The current six-month treatment for TB has remained unchanged for decades. Attempts to shorten this treatment have failed. In recent years, new drugs have been reported that could contribute to TB treatment in the near future, and are already being used in multi-drug-resistance TB.
Langendam, M.W.; van der Werf, M.J.; Huitric, E.; Manissero, D.
A potential threat to the success of new tuberculosis (TB) drugs is the development of resistance. Using drugs in appropriate regimens, such as those recommended in the World Health Organization (WHO) treatment guidelines, prevents the development of resistance. We performed a systematic review to assess the prevalence of inappropriate prescription of TB drugs for the treatment of TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Observational studies published from 2000 that included TB patients receiving treatment were selected. A treatment regimen was considered inappropriate if the regimen was not a WHO recommended regimen. 37 studies were included. Inappropriate treatment regimens were prescribed in 67% of studies. The percentage of patients receiving inappropriate regimens varied between 0.4% and 100%. In 19 studies the quality of treatment regimen reporting was low. Despite the fact that assessment of inappropriate treatment was hampered by low quality of reporting, our data indicate a reasonable amount of inappropriate prescription of TB treatment regimens. Thus, there is a risk that new drugs will be used in inappropriate treatment regimens, even with WHO guidelines in place, introducing the risk of resistance development. This article highlights the need to improve implementation of the WHO treatment of TB guidelines. PMID:22005923
Rifat, Mahfuza; Hall, John; Oldmeadow, Christopher; Husain, Ashaque; Hinderaker, Sven Gudmund; Milton, Abul Hasnat
Objective Previous tuberculosis (TB) treatment status is an established risk factor for multidrug-resistant TB (MDR-TB). This study explores which factors related to previous TB treatment may lead to the development of multidrug resistant in Bangladesh. Design We previously conducted a large case–control study to identify risk factors for developing MDR-TB in Bangladesh. Patients who had a history of previous TB treatment, either MDR-TB or non-MDR-TB, were interviewed about their previous treatment episode. This study restricts analysis to the strata of patients who have been previously treated for TB. Information was collected through face-to-face interviews and record reviews. Unadjusted and multivariable logistic regression was used for data analysis. Setting Central-level, district-level and subdistrict-level hospitals in rural and urban Bangladesh. Results The strata of previously treated patients include a total of 293 patients (245 current MDR-TB; 48 non-MDR-TB). Overall, 54% of patients received previous TB treatment more than once, and all of these patients were multidrug resistant. Patients with MDR-TB were more likely to have experienced the following factors: incomplete treatment (OR 4.3; 95% CI 1.7 to 10.6), adverse reactions due to TB treatment (OR 8.2; 95% CI 3.2 to 20.7), hospitalisation for symptoms associated with TB (OR 16.9; CI 1.8 to 156.2), DOTS (directly observed treatment, short-course) centre as treatment unit (OR 6.4; CI 1.8 to 22.8), supervised treatment (OR 3.8; CI 1.6 to 9.5); time-to-treatment centre (OR 0.984; CI 0.974 to 0.993). Conclusions Incomplete treatment, hospitalisation for TB treatment and adverse reaction are the factors related to previous TB treatment of patients with MDR-TB. Although the presence of supervised treatment (DOT), less time-to-treatment centres and being treated in DOTS centres were relatively higher among the patients with MDR-TB compared with patients without MDR-TB, these findings include information of
Dye, Christopher; Watt, Catherine J.; Bleed, Daniel
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
Kelly, P. M.
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
The authors analyze the results of surgical treatment for bilateral destructive pulmonary tuberculosis in 234 patients who have under- gone 449 lung operations. A study group comprised 156 patients who received mini-invasive surgical treatments via mini-accesses under video-assisted thoracoscopic control. A comparison group included 78 patients operated on through standard approaches by the conventional procedures. In the study group, surgery of less duration was attended by less blood loss, a need for fewer blood transfusions, and the lower incidence and severity of intraoperative complications. Complications following mini-invasive surgery occurred 4 times less frequently and postoperative mortality was 5 times less than that in the comparison group. With mini-invasive surgical techniques, a complete clinical effect at surgical hospital discharge was achieved 1.5-fold more frequently and it was more steady-state in the late period.
Harries, A. D.; Hargreaves, N. J.; Gausi, F.; Kwanjana, J. H.; Salaniponi, F. M.
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
Kumar, Mani Kant; Kumar, Prashant; Singh, Anjali
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
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
Choi, Rihwa; Jeong, Byeong-Ho
Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response. PMID:28028995
Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn
Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.
Heunis, J C; Kigozi, N G; van der Merwe, S; Chikobvu, P; Beyers, N
Contexte : Province de l'Etat Libre, Afrique du Sud.Objectif : Examiner les tendances en fonction du sexe de la nonconversion des frottis de crachats après 2 mois chez des nouveaux cas de tuberculose (TB) à frottis positifs pendant une période où la stratégie DOTS opérait.Schéma : Réalisation d'une étude rétrospective de cohorte des cas de TB enregistrés entre 2003 et 2009. La non-conversion était définie par un résultat de frottis positif après 2 mois de traitement. Des analyses descriptives et de modèles linéaires généralisés ont été réalisées et les tendances de non conversion à 2 mois en fonction du sexe ont été estimées.Résultats : Le taux d'ensemble de non conversion était de 12,5% chez les hommes et de 9,3% chez les femmes. La non conversion était significativement associée à l'âge chez les hommes (P < 0,001). Le taux de non conversion a significativement diminué entre 2003 et 2009 de 15,9% à 10,8% chez les hommes (P < 0,001) et de 12% à 6,6% chez les femmes (P < 0,001). Le taux moyen de déclin de la non-conversion était plus élevé chez les femmes à 1% (IC95% 0,8–1,2%) que chez les hommes à 0,8% (IC95% 0,5–1%). En 2009, le risque de non conversion était plus élevé de 60% chez les hommes (RR 1,60; IC95% 1,37–1,86).Conclusion : Le déclin de la tendance à la non-conversion du frottis de crachats après 2 mois de traitement a mis en évidence le succès relatif de la stratégie DOTS dans la lutte contre la TB, avec un meilleur résultat chez les femmes que chez les hommes. Les interventions devraient tenir compte du sexe et de l'âge des patients afin d'améliorer le taux de conversion du frottis de crachats à 2 mois.
Levin, A.; Felker, I.; Tceymach, E.; Krasnov, D.
SUMMARY BACKGROUND: In accordance with the existing hypothesis, the application of an endobronchial valve (EbV) leads to selective curative atelectasis of the affected part of the lung, contributing to early closure of cavities. OBJECTIVE: To assess the effect of EbV treatment on the course of tuberculosis (TB). METHODS: We compared the efficacy of EbV treatment and complex second-line treatment in treating patients with destructive pulmonary multidrug-resistant TB (MDR-TB). Bacteriological conversion and closure of cavities were selected as criteria to assess the effectiveness of EbV application. A total of 102 patients with destructive MDR-TB were enrolled into the study and randomly divided into two groups: 49 patients had an EbV installed (intervention group) and 53 patients received complex second-line treatment (control group). Complex chemotherapy was administered to both groups throughout the study period. RESULTS: The cure rate in the short- and long-term follow-up periods in the intervention group was shown to be much higher, 95.9% by bacteriological conversion and 67.3% by cavity closure. On comparison with the control group, this was respectively 37.7% and 20.7% (P < 0.0001). CONCLUSIONS: The application of EbV treatment can significantly improve the effectiveness of second-line chemotherapy regimens in MDR-TB patients. PMID:27776598
Morano, Jamie P; Walton, Mary R; Zelenev, Alexei; Bruce, R Douglas; Altice, Frederick L
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
With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other
Venkatesh, Kartik K; Swaminathan, Soumya; Andrews, Jason R; Mayer, Kenneth H
Globally, tuberculosis (TB) and HIV interact in deadly synergy. The high burden of TB among HIV-infected individuals underlies the importance of TB diagnosis, treatment and prevention for clinicians involved in HIV care. Despite expanding access to antiretroviral therapy (ART) to treat HIV infection in resource-limited settings, many individuals in need of therapy initiate ART too late and have already developed clinically significant TB by the time they present for care. Many co-infected individuals are in need of concurrent ART and anti-TB therapy, which dramatically improves survival, but also raises several management challenges, including drug interactions, shared drug toxicities and TB immune reconstitution inflammatory syndrome (IRIS). Due to the survival benefits of promptly initiating ART among all HIV-infected individuals, including those with TB, it is recommended that co-infected individuals receive treatment for both diseases, regardless of CD4+ cell count. We review current screening and treatment strategies for TB and HIV co-infection. Recent findings and ongoing studies will assist clinicians in managing the prevention and treatment of TB and HIV co-infection, which remains a major global health challenge.
Jacobs, Ruschca; Malherbe, Stephanus; Loxton, Andre G.; Stanley, Kim; van der Spuy, Gian; Walzl, Gerhard; Chegou, Novel N.
There is an urgent need for new tools for the rapid diagnosis of tuberculosis disease. We evaluated the potentials of 74 host markers as biomarkers for the immunological diagnosis of tuberculosis and monitoring of treatment response. Fifty-five individuals that presented with signs and symptoms requiring investigation for tuberculosis disease were prospectively recruited prior to clinical diagnosis, at a health centre in Cape Town, South Africa. Patients were later classified as having tuberculosis disease or other respiratory diseases (ORD) using a combination of clinical, radiological and laboratory findings. Out of 74 host markers that were evaluated in plasma samples from study participants using a multiplex platform, 18 showed potential as tuberculosis diagnostic candidates with the most promising being NCAM, CRP, SAP, IP-10, ferritin, TPA, I-309, and MIG, which diagnosed tuberculosis disease individually, with area under the ROC curve ≥0.80. Six-marker biosignatures containing NCAM diagnosed tuberculosis disease with a sensitivity of 100% (95%CI, 86.3-100%) and specificity of 89.3% (95%CI, 67.6-97.3%) irrespective of HIV status, and 100% accuracy in the absence of HIV infection. Furthermore, the concentrations of 11 of these proteins changed with treatment, thereby indicating that they may be useful in monitoring of the response to tuberculosis treatment. Our findings have potential to be translated into a point-of-care screening test for tuberculosis, after future validation studies. PMID:27557501
Harding, M J; Pilkington, P; Thomas, J
A survey of tuberculosis in Croydon between 1988 and 1991, using Chest Clinic health visitor records, showed that the disease occurred most frequently in those of Indian Sub-Continent (ISC) ethnic origin. Of the 222 cases during the 4-year period, 65% were of ISC ethnic origin, 22% were Caucasian and 11% Afro-Caribbean. Non-Caucasian cases were younger (P < 0.0001), and more likely to be female (P = 0.064) or present with non-pulmonary disease (P = 0.064). One-quarter of ISC patients developed active tuberculosis more than 15 years after immigration into the UK. Only seven cases were children. The contact tracing procedure resulted in three additional cases, all of whom were contacts of smear-positive index cases. There were significantly fewer Heaf or radiologically positive contacts of non-smear positive pulmonary, or non-pulmonary index cases (P = 0.0002). The value of the current contact tracing system is discussed.
Krishnamurthy, Gautham; Singh, Harjeet; Rajendran, Jayapal; Sharma, Vishal; Yadav, Thakur Deen; Gaspar, Balan Louis; Vasishta, Rakesh Kumar; Singh, Rajinder
Introduction: Gallbladder tuberculosis, in an endemic region, is a common infectious etiology affecting a rare organ. The high prevalence of carcinoma gallbladder in the endemic regions of tuberculosis, like India, poses diagnostic dilemma. Case series: We are reporting three cases of gallbladder tuberculosis mimicking carcinoma gallbladder of which the first two cases were operated with a presumptive diagnosis of malignancy. The third case presented to us after laparoscopic cholecystectomy elsewhere and on evaluation was found to have disseminated tuberculosis. Discussion: The lack of pathognomonic clinical and radiological characters results in histological surprise of gallbladder tuberculosis following surgery performed for other indications like malignancy. In preoperatively diagnosed patients medical management plays pivotal role in management. Surgery is required in symptomatic patients. On the other hand, histologically proven cases following surgical resection require antitubercular therapy. Conclusion: Previous history of tuberculosis or concomitant tuberculosis at other sites may provide clue to the diagnosis of biliary tuberculosis. Antitubercular treatment after surgery plays an important role in preventing further dissemination. PMID:28386408
Kakkar, Ashish Kumar; Dahiya, Neha
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.
Herrero, María Belén; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres
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.
Herrero, María Belén; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres
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
Kalo, Deepika; Kant, Surya; Srivastava, Kanchan; Sharma, Ajay K
Background: Tuberculosis (TB), a highly contagious disease that sees no gender, age, or race is mainly a disease of lungs. According to World Health Organization, a TB patient can be completely cured with 6–9 months of anti-TB treatment under directly observed treatment short course. Objectives: The aim of this study was to check the mono, multi- and triple-drug resistance to first line drugs (FLDs) among TB patients and to access their genetic profile using DR 3074, DR 0270, DR 0642, DR 2068, and DR 4110 using molecular techniques. Material and Methods: To gain a better understanding of drug resistant TB, we characterized 121 clinical isolates recovered from 159 drug resistant pulmonary tuberculosis patients by IS6110 genotyping. MTB isolates recovered from HIV- negative, and smear positive cases of both genders, age varied from 18 to 70 years with drug resistant-TB that was refractory to chemotherapy given for > 12 months. Of a total of 159 sputum smear positive patients sum number of male and female patients was 121 (76.10%) and 38 (23.89%), respectively. Among these patients, number of literate and illiterate patients were 123 (77.3%) and 36 (22.6%). 25 (15.7%) patients had farming as their occupation, 80 (50.3%) had nonagricultural occupation and 54 (33.9%) women were housewives. Results: Mono drug resistant, multi-drug resistant, and totally drug resistant (TDR) cases of TB were calculated as 113.83%, 125.1%, and 67.9%. Isoniazid showed the highest percentage of resistance among the patients. Conclusion: Any noncompliance to TB medications, lack of knowledge, and poor management in health centers, etc., results in the emergence of deadly direct repeat forms of TB, which are further complicated and complex to treat. PMID:28360464
Trigo, C; do Brasil, P E A A; Costa, M J M; de Castro, L
Occult hepatitis B virus infection (OBI) is characterized by the absence of HBsAg and persistence of the virus genome (HBV-DNA) in liver tissue and/or blood. OBI has been reported in several clinical contexts. However, the clinical significance of OBI in tuberculosis (TB) treatment is unknown. We investigated the OBI prevalence and its impact on the risk of drug-induced liver injury (DILI) during TB treatment. This was a prospective cohort study with one hundred patients who were treated for TB from 2008 to 2015. Laboratory, clinical and demographic data of TB patients were extracted from medical records. Based on HBV-DNA testing of serum samples, an OBI prevalence of 12% was established; almost half of these patients had both anti-HBc and anti-HBs serological markers. Low CD4(+) cell counts have been shown to be a risk factor for OBI among TB patients co-infected with HIV (P=.036). High DILI incidence was observed in this study. A multivariable Cox proportional hazard model was conducted and identified OBI (HR 2.98, 95% CI 1.30-6.86) as the strongest predictor for DILI when adjusted to CD4(+) cell count (HR 0.38, 95% CI 0.17-0.90), ALT before TB treatment (HR 1.37, 95% CI 0.81-2.32) and TB extrapulmonary clinical form (HR 2.91, 95% CI 1.75-7.21). The main aim of this study was to highlight DILI as a clinical outcome during treatment of TB patients with OBI. Therefore, HBV-DNA testing should be considered routinely in monitoring DILI, and also in other clinical implications associated with OBI, reduce morbidity and mortality.
Piñeros, A. R.; Campos, L. W.; Fonseca, D. M.; Bertolini, T. B.; Gembre, A. F.; Prado, R. Q.; Alves-Filho, J. C.; Ramos, S. G.; Russo, M.; Bonato, V. L. D.
The protective effects of mycobacterial infections on lung allergy are well documented. However, the inverse relationship between tuberculosis and type 2 immunity is still elusive. Although type 1 immunity is essential to protection against Mycobacterium tuberculosis it might be also detrimental to the host due to the induction of extensive tissue damage. Here, we determined whether lung type 2 immunity induced by allergen sensitization and challenge could affect the outcome of M. tuberculosis infection. We used two different protocols in which sensitization and allergen challenge were performed before or after M. tuberculosis infection. We found an increased resistance to M. tuberculosis only when allergen exposure was given after, but not before infection. Infected mice exposed to allergen exhibited lower bacterial load and cellular infiltrates in the lungs. Enhanced resistance to infection after allergen challenge was associated with increased gene expression of alternatively activated macrophages (M2 macrophages) and IL-33 levels. Accordingly, either adoptive transfer of M2 macrophages or systemic IL-33 treatment was effective in attenuating M. tuberculosis infection. Notably, the enhanced resistance induced by allergen exposure was dependent on IL-33 receptor ST2. Our work indicates that IL-33 might be an alternative therapeutic treatment for severe tuberculosis. PMID:28128217
Hanif, Shumaila N. M.; Garcia-Contreras, Lucila
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
Sokolov, N I; Evlashkin, D V; Karzhavina, G I
The diagnosed patients treated at an osseous tuberculosis hospital are analyzed. In the reporting period, the diagnosis of osseous tuberculosis has not been verified. Late detection of osseous tuberculosis, as its prehospital hyperdiagnosis is one of the main reasons of a grave condition in this group of patients. The paper characterizes plastic reparative versus palliative decompressive operations for tuberculous spondylitis with spinal-cord abnormalities and shows that radical surgery has a higher efficiency (89%) in the treatment of an inflammatory process and in the regression of neurological complications. In generalized forms of osteoarticular lesions if there is an indication for surgical treatment, long-term drug therapy for tuberculosis of the lung and other organs is not warranted.
Mesfin, Mengiste M; Newell, James N; Walley, John D; Gessessew, Amanuel; Madeley, Richard J
Background Delays seeking care increase transmission of pulmonary tuberculosis and hence the burden of tuberculosis, which remains high in developing countries. This study investigates patterns of health seeking behavior and determines risk factors for delayed patient consultation at public health facilities in 10 districts of Ethiopia. Methods New pulmonary TB patients ≥ 15 years old were recruited at 18 diagnostic centres. Patients were asked about their health care seeking behaviour and the time from onset of symptoms to first consultation at a public health facility. First consultation at a public health facility 30 days or longer after onset of symptoms was regarded as prolonged patient delay. Results Interviews were held with 924 pulmonary patients. Of these, 537 (58%) were smear positive and 387 (42%) were smear negative; 413 (45%) were female; 451 (49%) were rural residents; and the median age was 34 years. Prior to their first consultation at a public health facility, patients received treatment from a variety of informal sources: the Orthodox Church, where they were treated with holy water (24%); private practitioners (13%); rural drug vendors (7%); and traditional healers (3%). The overall median patient delay was 30 days (mean = 60 days). Fifty three percent [95% Confidence Intervals (CI) (50%, 56%)] of patients had delayed their first consultation for ≥ 30 days. Patient delay for women was 54%; 95% CI (54%, 58%) and men 51%; 95% CI (47%, 55%). The delay was higher for patients who used informal treatment (median 31 days) than those who did not (15 days). Prolonged patient delay (≥ 30 days) was significantly associated with both patient-related and treatment-related factors. Significant patient-related factors were smear positive pulmonary disease [Adjusted Odds Ratio (AOR) 1.4; 95% CI (1.1 to 1.9)], rural residence [AOR 1.4; 95% CI (1.1 to 1.9)], illiteracy [AOR 1.7; 95% CI (1.2 to 2.4)], and lack of awareness/misperceptions of causes of
Esmail, Hanif; Barry, Clifton E; Wilkinson, Robert J
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
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
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.
Raviglione, M. C.; Narain, J. P.; Kochi, A.
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
Hwang, Angela A; Lee, Bai-Yu; Clemens, Daniel L; Dillon, Barbara Jane; Zink, Jeffrey I; Horwitz, Marcus A
Tuberculosis is a major global health problem for which improved therapeutics are needed to shorten the course of treatment and combat emergence of drug resistance. Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of mononuclear phagocytes. As such, it is an ideal pathogen for nanotherapeutics because macrophages avidly ingest nanoparticles even without specific targeting molecules. Hence, a nanoparticle drug delivery system has the potential to target and deliver high concentrations of drug directly into M. tuberculosis-infected cells-greatly enhancing efficacy while avoiding off-target toxicities. Stimulus-responsive mesoporous silica nanoparticles of two different sizes, 100 and 50 nm, are developed as carriers for the major anti-tuberculosis drug isoniazid in a prodrug configuration. The drug is captured by the aldehyde-functionalized nanoparticle via hydrazone bond formation and coated with poly(ethylene imine)-poly(ethylene glycol) (PEI-PEG). The drug is released from the nanoparticles in response to acidic pH at levels that naturally occur within acidified endolysosomes. It is demonstrated that isoniazid-loaded PEI-PEG-coated nanoparticles are avidly ingested by M. tuberculosis-infected human macrophages and kill the intracellular bacteria in a dose-dependent manner. It is further demonstrated in a mouse model of pulmonary tuberculosis that the nanoparticles are well tolerated and much more efficacious than an equivalent amount of free drug.
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.
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
Mosquera-Restrepo, Sergio Fabián; Caro, Ana Cecilia; García, Luis F; Peláez-Jaramillo, Carlos Alberto; Rojas, Mauricio
The anti-mycobacterial immune response in adults and children with tuberculosis (TB), as well as the response in bacteriologically positive and negative patients, is different. However, knowledge of the immunological events occurring in the lungs in these clinical situations remains scarce. Exhaled breath condensate (EBC) samples may be useful for studying the inflammatory environment of the lower airways in TB patients. The fatty acid, cytokine, and chemokine profiles in EBC from healthy adults; smear-positive and smear-negative adult patients; and healthy, asthmatic, and TB children were determined using gas chromatography and LUMINEX, respectively. Unsaturated fatty acids, particularly oleate, were increased in TB adults and children compared with healthy individuals. Elevated levels of IL-17 were characteristic of paucibacillary patients (adults and children), whereas elevated MCP-1 (monocyte chemotactic protein-1) levels were characteristic of adult patients (smear-positive and smear-negative). The levels of all of the molecules were comparable to the controls after anti-TB treatment, suggesting that changes in the levels of the molecules detected in the EBC samples were the result of the active pulmonary TB. EBC samples may be an important tool for the detection of potential early biomarkers in the different clinical manifestations of pulmonary TB and a useful tool for the diagnosis of TB, particularly in children.
...: Developing Drugs for Treatment; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... industry entitled ``Pulmonary Tuberculosis: Developing Drugs for Treatment.'' The purpose of the draft guidance is to assist sponsors in the development of antimycobacterial drugs for the treatment of...
Lienhardt, Christian; Raviglione, Mario; Spigelman, Mel; Hafner, Richard; Jaramillo, Ernesto; Hoelscher, Michael; Zumla, Alimuddin; Gheuens, Jan
For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.
Rifat, Mahfuza; Rusen, I D; Mahmud, Mohammad Hasan; Nayer, Israt; Islam, Akramul; Ahmed, Faruque
In response to the global challenge of inadequate case detection of tuberculosis (TB), the Fund for Innovative DOTS Expansion through Local Initiatives to Stop Tuberculosis (FIDELIS) was developed in 2003 to rapidly assess and implement innovative approaches to increase the detection of new smear-positive TB cases. As previously reported, a wide range of target populations and interventions has been incorporated into successful FIDELIS projects.
Rifat, Mahfuza; Rusen, I. D.; Mahmud, Mohammad Hasan; Nayer, Israt; Islam, Akramul; Ahmed, Faruque
In response to the global challenge of inadequate case detection of tuberculosis (TB), the Fund for Innovative DOTS Expansion through Local Initiatives to Stop Tuberculosis (FIDELIS) was developed in 2003 to rapidly assess and implement innovative approaches to increase the detection of new smear-positive TB cases. As previously reported, a wide range of target populations and interventions has been incorporated into successful FIDELIS projects. PMID:18633095
Mahendradhata, Yodi; Syahrizal, Bobby M; Utarini, Adi
Background In year 2000, the entire population in Indonesia was 201 million and 57.6 percent of that was living in rural areas. This paper reports analyses that address to what extent the rural structure influence the way TB patients seek care prior to diagnosis by a DOTS facility. Methods We documented healthcare utilization pattern of smear positive TB patients prior to diagnosis and treatment by DOTS services (health centre, chest clinic, public and private hospital) in Yogyakarta province. We calculated the delay in treatment as the number of weeks between the onset of symptoms and the start of DOTS treatment. Statistical analysis was carried out with Epi Info version 3.3 (October 5, 2004). Results The only factor which was significantly associated with total delay was urban-rural setting (p = < 0.0001). The median total delay for TB patients in urban districts was 8 (1st Quartile = 4; 3rd Quartile = 12) weeks compared to 12 (1st Quartile = 7; 3rd Quartile = 23) weeks for patients in rural districts. Multivariate analysis suggested no confounding between individual factors and urban-rural setting remained as the main factor for total delay (p = < 0.0001). Primary health centre was the first choice provider for most (38.7%) of these TB patients. Urban-rural setting was also the only factor which was significantly associated with choice of first provider (p = 0.03). Conclusion Improving access to DOTS services in rural areas is an area of vital importance in aiming to make progress toward achieving TB control targets in Indonesia. PMID:19036164
Adams, Linda B.; Sinha, Indu; Franzblau, Scott G.; Krahenbuhl, James L.; Mehta, Reeta T.
The therapeutic efficacy of liposomal clofazimine (L-CLF) was studied in mice infected with Mycobacterium tuberculosis Erdman. Groups of mice were treated with either free clofazimine (F-CLF), L-CLF, or empty liposomes twice a week for five treatments beginning on day 1 (acute), day 21 (established), or day 90 (chronic) postinfection. One day after the last treatment, the numbers of CFU of M. tuberculosis in the spleen, liver, and lungs were determined. F-CLF at the maximum tolerated dose of 5 mg/kg of body weight was ineffective; however, 10-fold-higher doses of L-CLF demonstrated a dose response with significant CFU reduction in all tissues without any toxic effects. In acutely infected mice, 50 mg of L-CLF/kg reduced CFU 2 to 3 log units in all three organs. In established or chronic infection, treated mice showed no detectable CFU in the spleen or liver and 1- to 2-log-unit reduction in the lungs. A second series of L-CLF treatments cleared M. tuberculosis in all three tissues. L-CLF appears to be bactericidal in the liver and spleen, which remained negative for M. tuberculosis growth for 2 months. Thus, L-CLF could be useful in the treatment of tuberculosis. PMID:10390215
Sánchez, María D; García, Yoenis; Montes, Carlos; París, Sara C; Rojas, Mauricio; Barrera, Luis F; Arias, Mauricio A; García, Luis F
Alterations of monocyte/macrophages have been reported in patients with tuberculosis (TB), but their significance is poorly understood. Blood mononuclear cells from patients with different clinical forms of TB, at various times of anti-TB treatment, and healthy tuberculin positive individuals, were double-stained for CD14 plus CD206, TLR-2, IFN-gammaR1, CD40, HLA-DR, CD36 and CD163, and analyzed by flow cytometry. Monocytes were infected with Mycobacterium tuberculosis H37Rv and 24h later the phenotype, induction of necrosis and apoptosis and production of tumor necrosis factor TNFalpha, interleukin (IL)-10 and IL-12p40 were determined. TB patients presented higher percentage of CD14+ cells but lower percentage of CD14+DR+ and CD14+CD36+ cells. Expression of CD14, HLA-DR and CD36 was decreased in TB patients. Normal percentages and expression were restored during anti-TB treatment. Monocytes from TB patients underwent necrosis and apoptosis after M. tuberculosis infection, whereas monocytes from healthy controls exhibited only apoptosis. Anti-TB treatment reverted necrosis. There were no differences between the various clinical forms of TB. In vitro M. tuberculosis infection decreased expression of the membrane molecules studied. HLA-DR and CD36 inhibition correlated with induction of apoptosis. Restoration of monocyte alterations during anti-TB treatment suggests that such alterations may be caused by the high M. tuberculosis load present during active disease.
Mooventhan, A; Khode, Vitthal; Nivethitha, L
A 24-year-old, unmarried woman diagnosed of pulmonary tuberculosis (PTB) visited our hospital out-patient department in the month of August-2013. Patient came with the complaint of sever cough with expectoration; evening raise of temperature; gradual loss of appetite and weight since 2-weeks. We referred the patient to our hospital's Revised National Tuberculosis Program, direct observed treatment short-course center for sputum fluorescence microscopic examination (FME). FME report suggested the new smear positive, 2+ PTB. Our patient received yogic breathing techniques (YBT) for 45-min daily under the supervision for three alternate-days/week with anti-tuberculosis treatment (ATT) for the period of 8-weeks. After intervention our result showed better improvement in weight gain, body mass index, symptom scores, pulmonary function and health related quality of life with conversion of positive to negative FME for acid fast bacilli. It suggests YBT with ATT are effective in treating PTB and further studies required to warrant this effect.
Matos-Tocasca, Martha; De la Cruz-Ku, Gabriel; Auccacusi, Erick; Fernandez-Salas, Diego; García-Ahuanari, Tatiana; Valcarcel-Valdivia, Bryan
Case series Patient: Female, 28 • Male, 20 Final Diagnosis: Extensively drug-resistant tuberculosis Symptoms: Cough productive • dyspnea • hemoptysis • respiratory failure • weight loss Medication: — Clinical Procedure: — Specialty: Pulmonology Objective: Unusual clinical course Background: Extensively drug-resistant tuberculosis (XDR-TB) is a global problem due to the high morbidity and mortality it causes. Peru is one of the countries with the highest numbers of cases of XDR-TB, which increase every year. Case Report: We present the case of two siblings who developed XDR-TB, underwent surgery twice, and were in individualized treatment for more than 6 years. Finally they achieved remission of symptoms, despite not having standardized treatment schemes during their diagnosis period. Conclusions: Extensively drug-resistant tuberculosis can be cured with a treatment that involves both medical care and patient actions to achieve remission of the disease. PMID:27807339
Simonovska, Ljiljana; Ilievska-Popovska, Biljana
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
Opanasenko, M S; Levanda, L I; Kononenko, V A; KYimenko, V I; Tereshkovych, O V; Kalenychenko, M I; Konik, V M; Obrems'ka, O K; Demus, R S; Kshanovs'kyĭ, O E
Actual issue, concerning coexistent pulmonary tuberculosis and diabetes mellitus, was studied. The data about the rate of various types of diabetes mellitus in phthysiosurgery were adduced. The results of surgical treatment of 116 patients, suffering pulmonary tuberculosis on the diabetes mellitus background, were summarized. Total efficacy of the treatment have constituted 96.0%. The surgical complications rate was 12.2%.
Due to the implementation of the International Bank for Reconstruction and Development (IBRD) loan project "Prevention, diagnosis, treatment of tuberculosis and AIDS", a "Tuberculosis" component that is an addition to the national tuberculosis control program in 15 subjects of the Russian Federation, followed up by the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences, the 2005-2008 measures stipulated by the Project have caused substantial changes in the organization of tuberculosis control: implementation of Orders Nos. 109, 50, and 690 and supervision of their implementation; modernization of the laboratories of the general medical network and antituberbulosis service (404 kits have been delivered for clinical diagnostic laboratories and 12 for bacteriological laboratories, including BACTEC 960 that has been provided in 6 areas); 91 training seminars have been held at the federal and regional levels; 1492 medical workers have been trained in the detection, diagnosis, and treatment of patients with tuberculosis; 8 manuals and guidelines have been prepared and sent to all areas. In the period 2005-2008, the tuberculosis morbidity and mortality rates in the followed-up areas reduced by 1.2 and 18.6%, respectively. The analysis of patient cohorts in 2007 and 2005 revealed that the therapeutic efficiency evaluated from sputum smear microscopy increased by 16.3%; there were reductions in the proportion of patients having ineffective chemotherapy (from 16.1 to 11.1%), patients who died from tuberculosis (from 11.6 to 9.9%), and those who interrupted therapy ahead of time (from 11.8 to 7.8%). Implementation of the IBR project has contributed to the improvement of the national strategy and the enhancement of the efficiency of tuberculosis control.
Bastian, I.; Rigouts, L.; Van Deun, A.; Portaels, F.
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
Kaewseekhao, Benjawan; Naranbhai, Vivek; Roytrakul, Sittiruk; Namwat, Wises; Paemanee, Atchara; Lulitanond, Viraphong; Chaiprasert, Angkana; Faksri, Kiatichai
Biomarkers for determining clearance of Mycobacterium tuberculosis (Mtb) infection during anti-tuberculosis therapy or following exposure could facilitate enhanced monitoring and treatment. We screened for biomarkers indicating clearance of Mtb infection in vitro. A comparative proteomic analysis was performed using GeLC MSI/MS. Intracellular and secreted proteomes from activated THP-1 cells infected with the Mtb H37Rv strain (MOI = 1) and treated with isoniazid and rifampicin for 1 day (infection stage) and 5 days (clearance stage) were analyzed. Host proteins associated with early infection (n = 82), clearance (n = 121), sustained in both conditions (n = 34) and suppressed by infection (n = 46) were elucidated. Of the potential clearance markers, SSFA2 and CAECAM18 showed the highest and lowest protein intensities, respectively. A western blot of CAECAM18 validated the LC MS/MS result. For three clearance markers (SSFA2, PARP14 and PSME4), in vivo clinical validation was concordantly reported in previous patient cohorts. A network analysis revealed that clearance markers were enriched amongst four protein interaction networks centered on: (i) CD44/CCND1, (ii) IFN-β1/NF-κB, (iii) TP53/TGF-β and (iv) IFN-γ/CCL2. After infection, proteins associated with proliferation, and recruitment of immune cells appeared to be enriched possibly reflecting recruitment of defense mechanisms. Counteracting proteins (CASP3 vs. Akt and NF-κB vs. TP53) associated with apoptosis regulation and its networks were enriched among the early and sustained infection biomarkers, indicating host-pathogen competition. The BRCA1/2 network was suppressed during infection, suggesting that cell proliferation suppression is a feature of Mtb survival. Our study provides insights into the mechanisms of host-Mtb interaction by comparing the stages of infection clearance. The identified clearance biomarkers may be useful in monitoring tuberculosis treatment.
Cox, Helen Suzanne; Orozco, Juan Daniel; Male, Roy; Ruesch-Gerdes, Sabine; Falzon, Dennis; Small, Ian; Doshetov, Darebay; Kebede, Yared; Aziz, Mohammed
Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB.
Orozco, Juan Daniel; Male, Roy; Ruesch-Gerdes, Sabine; Falzon, Dennis; Small, Ian; Doshetov, Darebay; Kebede, Yared; Aziz, Mohammed
Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB. PMID:15200821
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
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.
Raju, Ravikiran M; Raju, Sagar M; Zhao, Yanlin; Rubin, Eric J
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.
Orenstein, Evan W; Basu, Sanjay; Shah, N Sarita; Andrews, Jason R; Friedland, Gerald H; Moll, Anthony P; Gandhi, Neel R; Galvani, Alison P
Multidrug-resistant (MDR) tuberculosis is a growing clinical and public-health concern. To evaluate existing evidence regarding treatment regimens for MDR tuberculosis, we used a Bayesian random-effects meta-analysis of the available therapeutic studies to assess how the reported proportion of patients treated successfully is influenced by differences in treatment regimen design, study methodology, and patient population. Successful treatment outcome was defined as cure or treatment completion. 34 clinical reports with a mean of 250 patients per report met the inclusion criteria. Our analysis shows that the proportion of patients treated successfully improved when treatment duration was at least 18 months, and if patients received directly observed therapy throughout treatment. Studies that combined both factors had significantly higher pooled success proportions (69%, 95% credible interval [CI] 64-73%) than other studies of treatment outcomes (58%, 95% CI 52-64%). Individualised treatment regimens had higher treatment success (64%, 95% CI 59-68%) than standardised regimens (54%, 95% CI 43-68%), although the difference was not significant. Treatment approaches and study methodologies were heterogeneous across studies. Many important variables, including patients' HIV status, were inconsistently reported between studies. These results underscore the importance of strong patient support and treatment follow-up systems to develop successful MDR tuberculosis treatment programmes.
Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions.
Shen, Gwan-Han; Tsao, Thomas Chang-Yao; Kao, Shang-Jyh; Lee, Jen-Jyh; Chen, Yen-Hsu; Hsieh, Wei-Chung; Hsu, Gwo-Jong; Hsu, Yen-Tao; Huang, Ching-Tai; Lau, Yeu-Jun; Tsao, Shih-Ming; Hsueh, Po-Ren
The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1-7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥ 7 days) of symptoms, a history of night sweats, lack of fever (> 38 °C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB.
Mohammed, Shama; Glennerster, Rachel; Khan, Aamir J.
Importance The rapid uptake of mobile phones in low and middle-income countries over the past decade has provided public health programs unprecedented access to patients. While programs have used text messages to improve medication adherence, there have been no high-powered trials evaluating their impact on tuberculosis treatment outcomes. Objective To measure the impact of Zindagi SMS, a two-way SMS reminder system, on treatment success of people with drug-sensitive tuberculosis. Design We conducted a two-arm, parallel design, effectiveness randomized controlled trial in Karachi, Pakistan. Individual participants were randomized to either Zindagi SMS or the control group. Zindagi SMS sent daily SMS reminders to participants and asked them to respond through SMS or missed (unbilled) calls after taking their medication. Non-respondents were sent up to three reminders a day. Setting Public and private sector tuberculosis clinics in Karachi, Pakistan. Participants Newly-diagnosed patients with smear or bacteriologically positive pulmonary tuberculosis who were on treatment for less than two weeks; 15 years of age or older; reported having access to a mobile phone; and intended to live in Karachi throughout treatment were eligible to participate. We enrolled 2,207 participants, with 1,110 randomized to Zindagi SMS and 1,097 to the control group. Main Outcome The primary outcome was clinically recorded treatment success based upon intention-to-treat. Results We found no significant difference between the Zindagi SMS or control groups for treatment success (719 or 83% vs. 903 or 83%, respectively, p = 0·782). There was no significant program effect on self-reported medication adherence reported during unannounced visits during treatment. Conclusion In this large-scale randomized controlled effectiveness trial of SMS medication reminders for tuberculosis treatment, we found no significant impact. Trial Registration The trial was registered with ClinicalTrials.gov, NCT
Swanson, Rosemary V.; Ammerman, Nicole C.; Ngcobo, Bongani; Adamson, John; Moodley, Chivonne; Dorasamy, Afton; Moodley, Sashen; Mgaga, Zinhle; Bester, Linda A.; Singh, Sanil D.; Almeida, Deepak V.
Experimental and clinical studies have indicated that the antileprosy drug clofazimine may contribute treatment-shortening activity when included in tuberculosis treatment regimens. Clofazimine accumulates to high levels in tissues, has a long half-life, and remains in the body for months after administration is stopped. We hypothesized that in tuberculosis treatment, accumulated clofazimine may contribute sustained antimicrobial activity after treatment cessation, and we used the BALB/c mouse model of chronic tuberculosis chemotherapy to address this hypothesis. Mycobacterium tuberculosis-infected mice were treated for 4 weeks or 8 weeks with either isoniazid alone, clofazimine alone, the first-line regimen rifampin-isoniazid-pyrazinamide-ethambutol, or a first-line regimen where clofazimine was administered in place of ethambutol. To evaluate posttreatment antimicrobial activity, bacterial regrowth in the lungs and spleens was assessed at the day of treatment cessation and 2, 4, 6, and 8 weeks after treatment was stopped. Bacterial regrowth was delayed in all mice receiving clofazimine, either alone or in combination, compared to the mice that did not receive clofazimine. This effect was especially evident in mice receiving multidrug therapy. In mice not receiving clofazimine, bacterial regrowth began almost immediately after treatment was stopped, while in mice receiving clofazimine, bacterial regrowth was delayed for up to 6 weeks, with the duration of sustained antimicrobial activity being positively associated with the time that serum clofazimine levels remained at or above the 0.25-μg/ml MIC for M. tuberculosis. Thus, sustained activity of clofazimine may be important in the treatment-shortening effect associated with this drug. PMID:26926638
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
Volmink, J.; Garner, P.
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
Lai, Yun-Ju; Yen, Yung-Feng
Background The association between body mass index and mortality in patients with tuberculosis has not been extensively studied, and the existing evidence is inconsistent. This study aimed to investigate the impact of body mass index on timing of death in patients with tuberculosis. Methods All Taiwanese adults with tuberculosis in Taipei, Taiwan, were included in a retrospective cohort study in 2011–2012. Multinomial logistic regression was used to evaluate the association between body mass index and timing of death in patients with tuberculosis. Results Among 1557 eligible patients, 84.1% (1310), 8.2% (128), and 7.6% (119) underwent successful treatment, early death, and late death, respectively. The mean age of the patients with tuberculosis was 64.2 years old, and 67.7% were male. After controlling for potential confounding variables, underweight with body mass index less than 18.5 kg/ m2 was significantly associated with elevated risk of all-cause mortality [Adjusted odds ratio (AOR), 1.64; 95% confidence interval (CI), 1.17–2.30]. Considering timing of death, underweight with body mass index less than 18.5 was significantly associated only with elevated risk of early mortality within the first 8 weeks of treatment onset (AOR, 2.22; 95% CI, 1.45–3.40) Conclusions For patients with tuberculosis infection, underweight with body mass index less than 18.5 kg/ m2 is an independent predictor for early mortality within the first 8 weeks of treatment. PMID:28085951
The Tuberculosis Surveillance Center (TSC) at the Research Institute of Tuberculosis has published a series of annual reports on tuberculosis (TB) statistics in Japan since 2008. These reports are based on information on the nationwide computerized TB surveillance system database, which has been in operation since 1987. This is the first of a new series of reports for the "TB Annual Report 2011" that includes a summary of TB statistics and an overview of TB cases with foreign nationality in 2011. A total of 22,681 cases with all types of TB were notified in 2011 with a notification rate of 17.7 per 100,000 population. The TB notification rates decreased to less than 20 per 100,000 population in 2007 and continued to decline until 2011. A total of 8,654 sputum-smear positive pulmonary TB were notified in 2011, at a rate of 6.8 per 100,000 population. The number of latent TB infection (LTBI) cases requiring prophylactic treatment drastically increased from 4,930 cases in 2010 to 10,046 cases in 2011. Surveillance data on TB cases with foreign nationality in Japan have been collected since 1998. The number of TB cases with foreign nationality increased from 739 in 1998 to 931 in 2004 but has been stagnated since then, that indicated 921 in 2011. The TB cases with foreign nationality accounted for 2.1 % of all new TB cases in 1998, and this percentage increased to 4.1% in 2011. Of note, new TB cases with foreign nationality aged 20-29 years accounted for 30.0% of all new TB cases among the same age group in 2011. Among the TB cases with foreign nationality, more than half were from China (29.6%) and the Philippines (23.7%) taken together. In most cases, foreign nationals developed TB within 5 years of entry into Japan, including 80.0% of those aged 10-19 years and 80.8% of those aged 20-29 years. Of these TB cases with foreign nationality, 27% were noted in full-time employees, followed by unemployed persons (21%) and students (20%). With an increase in the number of
Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; Kirschner, Denise E.
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.
Rawal, Gautam; Baxi, Mudit
The developing countries are having an abruptly growing number of drug resistant tuberculosis cases. Multidrug-resistant tuberculosis (MDR-TB) is a type of TB in which the strain of Mycobacterium tuberculosis is resistant to at least Isoniazid and Rifampicin, the two most effective of the four first-line TB drugs (the other two drugs being Ethambutol and Pyrazinamide). The management of such cases is complex and requires a treatment for 24-27 months. The current guidelines available for the management of this type of TB are largely based on the second line TB drugs which are relatively costly, less efficacious and are associated with greater side-effects. The introduction of newer drugs to cater to the high mortality and early sputum culture conversion in the MDR-TB cases is an absolute essential. In the present article, the authors discuss about the introduction of a newer drug named Bedaquiline for the control of MDR-TB. PMID:27656462
Satyanarayana, Srinath; Pai, Madhukar; Thomas, Beena E.; Chadha, Vineet K.; Swaminathan, Soumya; Mayer, Kenneth H.
Background India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world’s “missing” patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The “cascade of care” is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions. Methods and Findings The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India’s TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014–2015), one WHO dataset (2015), and three RNTCP reports (2014–2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000–2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB—including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB. The WHO estimated that there were 2,700,000 (95%CI: 1,800,000–3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775–1
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.
Zhang, Simin; Peng, Xianzhen; Zheng, Xianzhi; Xu, Guisheng; Wang, Min; Wang, Jianming; Lu, Hui
Objective China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. Methods There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. Results The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983–6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of
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
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
Story, A; Murad, S; Roberts, W; Verheyen, M; Hayward, A C
Background The control of tuberculosis (TB) is founded on early case detection and complete treatment of disease. In the UK, TB is concentrated in subgroups of the population in large urban centres. The impact of homelessness, imprisonment and problem drug use on TB control in London is reviewed. Methods A cohort study was undertaken of all patients with TB in Greater London to determine the point prevalence of disease in different groups and to examine risk factors for smear positivity, drug resistance, treatment adherence, loss to follow‐up and use of directly observed therapy (DOT). Results Data were collected on 97% (1941/1995) of eligible patients. The overall prevalence of TB was 27 per 100 000. An extremely high prevalence of TB was seen in homeless people (788/100 000), problem drug users (354/100 000) and prisoners (208/100 000). Multivariate analysis showed that problem drug use was associated with smear positive disease (OR 2.2, p<0.001), being part of a known outbreak of drug resistant TB (OR 3.5, p = 0.001) and loss to follow‐up (OR 2.7, p<0.001). Imprisonment was associated with being part of the outbreak (OR 10.3, p<0.001) and poor adherence (OR 3.9, p<0.001). Homelessness was associated with infectious TB (OR 1.6, p = 0.05), multidrug resistance (OR 2.1, p = 0.03), poor adherence (OR 2.5, p<0.001) and loss to follow‐up (OR 3.8, p<0.001). In London, homeless people, prisoners and problem drug users collectively comprise 17% of TB cases, 44% of smear positive drug resistant cases, 38% of poorly compliant cases and 44% of cases lost to follow‐up. 15% of these patients start treatment on DOT but 46% end up on DOT. Conclusions High levels of infectious and drug resistant disease, poor adherence and loss to follow‐up care indicate that TB is not effectively controlled among homeless people, prisoners and problem drug users in London. PMID:17289861
Brancker, A; Enarson, D A; Grzybowski, S; Hershfield, E S; Jeanes, C W
This report marks over 50 years of publication by Statistics Canada of annual reports on tuberculosis statistics. These years have witnessed what has been described as a conquest of tuberculosis in Canada. To quote George Jasper Wherrett in The Miracle of the Empty Beds: One hundred years ago the word consumption (as tuberculosis was then called) struck horror in human hearts. Today, in the western world, it barely evokes any emotion save a too easy surprise that it still exists. This statistical chronicle of tuberculosis in Canada is divided into two parts. Part I: From the Era of Sanatorium Treatment to the Present pulls together data from yellowed-with-age reports on tuberculosis and vital statistics, historical accounts and modern computer files, to document the changes in tuberculosis incidence and mortality over past decades to the present. Part II: Risk Today and Control takes a closer look at those most vulnerable to contracting tuberculosis. It also looks at the future, the need for maintaining and, indeed, strengthening vigilance, and the work yet to be done to eradicate tuberculosis in Canada. The fight against tuberculosis is far from over.
Chadha, V K
High prevalence and incidence of disease and a high rate of transmission of infection characterise the tuberculosis (TB) situation in India. Disease surveys conducted in different parts of the country since the 1950s have reported prevalences of smear-positive pulmonary TB (PTB) of 0.6-7.6 per 1000 population, culture-positive TB of 1.7-9.8 and culture and/or smear-positive TB of 1.8-12.7. The incidence of smear-positive PTB has been observed in the range of 1.0-1.6/1000 and that of culture-positive PTB 1.0-2.5/1000 in the limited number of studies carried out. The annual risk of tuberculous infection (ARTI) had been estimated at 1-2% for most of the tuberculin surveys carried out in different areas over different time periods. During a nationwide study in 2000-2003, the average ARTI in the country was estimated at 1.5%. An increasing trend has been observed in human immunodeficiency virus (HIV) seropositivity among TB cases, which has been found to vary between 0.4% and 28.8% in different studies conducted mostly at tertiary health care centres. The proportion of new cases with multidrug resistance (MDR) was relatively low, at 0.5-5.3%. However, the proportion of MDR cases among previously treated cases varied between 8% and 67%.
Mel'nyk, V P; Anisimova, Iu M; Borovs'kyĭ, V R; Stadnyk, L V; Svitlychna, T H
Results of clinical and laboratoty studies on efficiency and safety of upplied soya-based food during intensive antimicobacterial treatment of patients with tuberculosis are presented in the article. Obtained results showed the necessity of introduction soya-based food in a complex treatment of this infection as it enhances processes of detoxication, positevely influences on functional and structural state of the liver, reduces cytolysis, cholestasis symptomes, mesenchymal and inflamation reactions thus increases the tolerance of antimicobacterial agents.
Silva, João P; Gonçalves, Carine; Costa, César; Sousa, Jeremy; Silva-Gomes, Rita; Castro, António G; Pedrosa, Jorge; Appelberg, Rui; Gama, F Miguel
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.
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
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
Okabayashi, Ken; Nishio, Kazumi; Aida, Shinji; Nakano, Yasushi
A 27-year-old man with a 4-month history of treatment for miliary tuberculosis at another hospital was admitted to our hospital for continued treatment. Computed tomography showed new lesions in the S8 area of the liver and spleen, despite resolution of chest radiographic findings. Because these new lesions were still present after 8 months of treatment, we performed laparoscopic drainage of the liver abscess. Purulent material drained from the lesion revealed positive polymerase chain reaction results for Mycobacterium tuberculosis, and identification of granuloma with infiltrating lymphocytes and plasma cells confirmed the diagnosis of tubercular liver abscess. Pathological changes in the spleen over the clinical course were also regarded as representing tubercular abscess. Postoperative course was good, and tuberculosis treatment ended after 12 months. Tubercular liver abscess subsequently showed prominent reduction, and the tubercular splenic abscess disappeared on abdominal ultrasonography. Tubercular hepatosplenic abscesses appearing during tubercular treatment are rare. We report this valuable case in which laparoscopic drainage of a liver abscess proved useful for diagnosis and treatment.
Karam-Bechara, J; Naime-Libien, J E; Posada-Maldonado, E E; Aroch-Calderón, A; Olvera, R
This paper presents the results of a five year follow-up study of a cohort of children under fifteen years of age with tuberculosis. One group received standard treatment, and the other group received short course treatment. In the standard group there were four treatment failures, while in the other group, all the subjects had an excellent evolution and there were no failures. There was not a statistically significant difference regarding treatment failures, it is recommended, however, to carry out similar studies with greater sample sizes in order to determine the benefits of the short course treatment.
Zeka, Arzu N; Tasbakan, Sezai; Cavusoglu, Cengiz
Mycobacterium tuberculosis remains one of the most significant causes of death from an infectious agent. The rapid diagnosis of tuberculosis and detection of rifampin (RIF) resistance are essential for early disease management. The GeneXpert MTB/RIF assay is a novel integrated diagnostic device for the diagnosis of tuberculosis and rapid detection of RIF resistance in clinical specimens. We determined the performance of the MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in smear-positive and smear-negative pulmonary and extrapulmonary specimens obtained from possible tuberculosis patients. Two hundred fifty-three pulmonary and 176 extrapulmonary specimens obtained from 429 patients were included in the study. One hundred ten (89 culture positive and 21 culture negative for M. tuberculosis) of the 429 patients were considered to have tuberculosis. In pulmonary specimens, sensitivities were 100% (27/27) and 68.6% (24/35) for smear-positive and smear-negative specimens, respectively. It had a lower sensitivity with extrapulmonary specimens: 100% for smear-positive specimens (4/4) and 47.7% for smear-negative specimens (21/44). The test accurately detected the absence of tuberculosis in all 319 patients without tuberculosis studied. The MTB/RIF assay also detected 1 RIF-resistant specimen and 88 RIF-susceptible specimens, and the results were confirmed by drug susceptibility testing. We concluded that the MTB/RIF test is a simple method, and routine staff with minimal training can use the system. The test appeared to be as sensitive as culture with smear-positive specimens but less sensitive with smear-negative pulmonary and extrapulmonary specimens that include low numbers of bacilli.
Moreno, Antonio; Sánchez, Francesca; Nelson, Jeanne; Miró, José M; Caylà, Joan A
New treatment guidelines are required to improve the tuberculosis control strategies that have been used for 30 years. Seven centers of the Barcelona Tuberculosis Research Unit (BTRU) (Unitat d'Investigació en Tuberculosi de Barcelona) are collaborating with the Division of Tuberculosis Elimination of the United States Centers for Disease Control and Prevention in a series of clinical trials on latent tuberculosis infection and tuberculosis disease. BTRU participation began in 2004 with Study 26, an evaluation of the efficacy and tolerability of rifapentine plus isoniazid administered once weekly for 3 months compared with the standard treatment for latent tuberculosis infection. The BTRU centers together enrolled 246 patients (3% of the total). General enrollment was completed in February, 2008. HIV-infected patient and child enrollment continues. Treatment with 12 doses instead of 270 doses is expected to be a clear success. However, the analysis will be completed in 2010. Study 28 (started in 2006), designed for the treatment of pulmonary tuberculosis, compared standard treatment with an experimental regimen substituting moxifloxacin for isoniazid. BTRU centers together enrolled 15 patients (3.5% of the total). The provisional results (presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, 2007) showed no difference between the sputum conversion rate of each regimen at week 8 of treatment. Study 29 is currently underway, in which rifapentine was introduced in the experimental regimen for active tuberculosis treatment.
Ruiz Del Olmo Izuzquiza, Ignacio; Orden Rueda, Claudia; Ochoa Gómez, Laura; Clavero Montañés, Nuria; Berdún Chéliz, Enrique; Guerrero Laleona, Carmelo
Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started. Twenty-one days later she presented high fever with no other symptoms, worsening of radiological findings and normal blood tests, serologies and brain magnetic resonance imaging. The patient presented a paradoxical reaction and was given prednisone 1 mg/kg/day, fever disappeared in 24 hours. It is important to consider a paradoxical reaction when other causes of clinical and/or radiological worsening have been ruled out, to avoid unnecessary tests and treatment modifications.
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
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
Kargarpour Kamakoli, Mansour; Sadegh, Hamid Reza; Farmanfarmaei, Ghazaleh; Masoumi, Morteza; Fateh, Abolfazl; Javadi, Gholamreza; Rahimi Jamnani, Fatemeh; Vaziri, Farzam; Siadat, Seyed Davar
Mixed strain infections of Mycobacterium tuberculosis make diagnosis, treatment, and control of tuberculosis (TB) more difficult. This study was aimed to evaluate the relationship between mixed infections, antibiotic resistance patterns and treatment of TB patients. In this study, among 2850 suspected TB clinical samples, a total of ninety-six clinical samples from 66 TB confirmed patients were subjected to the 24-locus variable-number tandem repeat method to evaluate the prevalence of mixed infections. For all studied strains, 288 colonies (three individual clones for each sample) were isolated from different colonies and separately analyzed by the Drug Susceptibility Test (DST). For all patients, follow up was done after 6 months of treatment. Based on direct 24 loci MIRU-VNTR, in the 66 TB patients, 53% (35/66) showed mixed infection. In the mixed samples, 45.71% (16/35) showed different antibiotic resistant patterns. Among the mixed infection patients, eight (22.9%; 8/35) showed treatment failure after six- month therapy. Six of these non-treated patients (75%; 6/8) had different antibiotic resistant patterns. We conclude that mixed infections, have a negative impact on treatment of TB patients especially when co-infecting M. tuberculosis strains display heteroresistance. PMID:28120910
Pachi, Argiro; Bratis, Dionisios; Moussas, Georgios; Tselebis, Athanasios
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
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
This PhD thesis is based on 5 studies conducted in the period 2006-2010 during my employment at the International Reference Laboratory of Mycobacteriology, Statens Serum Institut. The overall aim was to assess tuberculosis (TB) treatment in Denmark with specific focus on the risk of relapse of TB disease, and to analyse treatment outcome of patients with multidrug-resistant (MDR) or isoniazid-resistant TB. The project established the need for rapid methods to detect resistance and follow-up of treatment. A rapid method to detect drug resistance was optimised and evaluated for use directly in clinical specimens. The studies were based on data from the Mycobacterial registry in the period 1992-2007, which included the results from microscopy, culture, drug-susceptibility and restriction fragment length polymorphism (RFLP). Information on dates of death/emigration were taken from the CPR-registry and treatment from surveillance data and patient records. The rate of recurrent TB was found to be low in Denmark, during 13.5 years of follow-up. Relapse accounted for 1.3% of the recurrent cases and reinfection was rare, only in 0.5% cases. The relapse hazard increased up to four years after diagnosis. Cavitary disease was associated with relapse as opposed to reinfection and may need prolonged treatment and closer monitoring. The incidence of MDR-TB and isoniazid resistance was confirmed to be low. Successful short- and long-term treatment outcome of MDR-TB and isoniazid-resistant TB was high. High- and low-level isoniazid resistance did not affect treatment outcome. A multiplex PCR hybridization mutation analysis, that simultaneously detects the most frequent rpoB and katG gene mutations conferring rifampin and high-level isoniazid resistance, was optimized for direct use and evaluated in smear-positive specimens as opposed to slow conventional drug-susceptibility testing (DST). The second-generation rifampin and isoniazid resistance mutation assay additionally included
Frolov, G A; Popkova, N L; Kalashnikov, A V
Analysis of the results of surgical treatment in 105 patients with pulmonary tuberculosis revealed that 25 patients had postoperative complications. Complications, outcomes, dysfunctions, and life quality were analyzed in late postoperative periods after 4 types of operations: segmentectomy (n = 52), lobectomy (n = 26), pulmonectomy (n = 12), palliative operations (n = 15). The best immediate and long-term results were achieved after segmentectomy in patients with antibiotic-sensitive forms of MBT.
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
Cordier-Lassalle, Thierry; Keravec, Joel
Abstract Problem Many countries have limited experience of securing the best prices for drugs and have little negotiating power. This is particularly true for the complex, lengthy and expensive regimens used to treat multidrug-resistant tuberculosis. Approach The Stop TB Partnership’s Global Drug Facility is dedicated to improving worldwide access to antituberculosis medicines and diagnostic techniques that meet international quality standards. Local setting The Global Drug Facility is able to secure price reductions through competitive tendering among prequalified drug manufacturers and by consolidating orders to achieve large purchase volumes. Consolidating the market in this way increases the incentives for suppliers of quality-assured medicines. Relevant changes In 2013 the Global Drug Facility reduced the price of the second-line drugs it supplies for multidrug-resistant tuberculosis: the overall cost of the longest and most expensive treatment regimen for a patient decreased by 26% – from 7890 United States dollars (US$) in 2011 to US$ 5822 in 2013. Lessons learnt The price of treatment for multidrug-resistant tuberculosis supplied by the Global Drug Facility was reduced by consolidating orders to achieve large purchase volumes, by international, competitive bidding and by the existence of donor-funded medicine stockpiles. The rise in the number of suppliers of internationally quality-assured drugs was also important. The savings achieved from lower drug costs could be used to increase the number of patients on high-quality treatment. PMID:26229192
Caminero, José A
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.
Porco, Travis C; Lewis, Bryan; Marseille, Elliot; Grinsdale, Jennifer; Flood, Jennifer M; Royce, Sarah E
Background Immigrants to the U.S. are required to undergo overseas screening for tuberculosis (TB), but the value of evaluation and treatment following entry to the U.S. is not well understood. We determined the cost-effectiveness of domestic follow-up of immigrants identified as tuberculosis suspects through overseas screening. Methods Using a stochastic simulation for tuberculosis reactivation, transmission, and follow-up for a hypothetical cohort of 1000 individuals, we calculated the incremental cost-effectiveness of follow-up and evaluation interventions. We utilized published literature, California Reports of Verified Cases of Tuberculosis (RVCTs), demographic estimates from the California Department of Finance, Medicare reimbursement, and Medi-Cal reimbursement rates. Our target population was legal immigrants to the United States, our time horizon is twenty years, and our perspective was that of all domestic health-care payers. We examined the intervention to offer latent tuberculosis therapy to infected individuals, to increase the yield of domestic evaluation, and to increase the starting and completion rates of LTBI therapy with INH (isoniazid). Our outcome measures were the number of cases averted, the number of deaths averted, the incremental dollar cost (year 2004), and the number of quality-adjusted life-years saved. Results Domestic follow-up of B-notification patients, including LTBI treatment for latently infected individuals, is highly cost-effective, and at times, cost-saving. B-notification follow-up in California would reduce the number of new tuberculosis cases by about 6–26 per year (out of a total of approximately 3000). Sensitivity analysis revealed that domestic follow-up remains cost-effective when the hepatitis rates due to INH therapy are over fifteen times our best estimates, when at least 0.4 percent of patients have active disease and when hospitalization of cases detected through domestic follow-up is no less likely than
Win, A N; Edginton, M E; Hinderaker, S G; Minn, N N; Linn, A K
The objectives of this retrospective cohort study were to report treatment outcomes and identify factors associated with treatment failure among all retreatment tuberculosis (TB) patients registered in the public-private mix DOTS programme of Populations Services International-Myanmar over 6 years. Among 3643 retreatment patients, 2657 (73%) were successfully treated and 309 (8.5%) failed. This study shows that retreatment patients who have failed treatment for their first TB episode are almost twice as likely to fail a second time (13.5%). We have identified some key programmatic challenges associated with retreatment TB in the private sector, and steps are being taken to address this issue.
Yuhara, Lucia Suemi; Sacchi, Flávia Patussi Correia; Croda, Julio
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
Schwitters, A.; Kaggwa, M.; Omiel, P.; Nagadya, G.; Kisa, N.; Dalal, S.
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
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
Annual reports of tuberculosis (TB) statistics in Japan have been compiled mainly using the output of the database obtained through the nationwide computerized tuberculosis surveillance system which has been operated since 1987. This system has been revised several times, with the latest revision conducted in 2007 when much new information was added. Therefore, a plan was drawn up to provide TB epidemiological statistics in Japan on "Kekkaku" and a series of ten reports was already issued as "TB Annual Report 2008". This is the first report of a new series for "TB Annual Report 2009". The report can be summarized as follows. The TB notification (incidence) rate fell below 20 per 100,000 in 2007 and continued to decline, reaching 19.0 in 2009. However, 24,170 TB patients were newly notified in 2009. For sputum smear positive pulmonary TB, the patient count was 9,675 with an incidence rate of 7.6 per 100,000 in 2009. Since June 2007, it has been legally compulsory to notify latent TB infections (LTBI) requiring treatment; the number in 2009 was 4119 cases.
Prasad, B M; Satyanarayana, S; Chadha, S S; Das, A; Thapa, B; Mohanty, S; Pandurangan, S; Babu, E R; Tonsing, J; Sachdeva, K S
In India, to increase tuberculosis (TB) case detection under the National Tuberculosis Programme, active case finding (ACF) was implemented by the Global Fund-supported Project Axshya, among high-risk groups in 300 districts. Between April 2013 and December 2014, 4.9 million households covering ~20 million people were visited. Of 350 047 presumptive pulmonary TB cases (cough of ⩾2 weeks) identified, 187 586 (54%) underwent sputum smear examination and 14 447 (8%) were found to be smear-positive. ACF resulted in the detection of a large number of persons with presumptive pulmonary TB and smear-positive TB. Ensuring sputum examination of all those with presumptive TB was a major challenge.
Libonati, J.P.; Stager, C.E.; Davis, J.R.; Siddiqi, S.H.
Direct-drug-susceptibility tests were performed on clinical specimens positive for acid-fast bacilli by either Ziehl-Neelsen or fluorochrome staining. The results of conventional agar dilution and a modified radiometric (BACTEC) method were compared. A total of 580 smear-positive specimens were tested by the BACTEC method at three separate sites. Three hundred and seventy-seven of these were culture positive for M. tuberculosis, and 343 (91%) yielded acceptable direct-susceptibility-test results. We used the conventional method to determine that 343 of 519 smear-positive specimens were culture positive for M. tuberculosis, and 212 (62%) produced acceptable results within 3 wks. Conventional results were reported in 3-4 wks, while the time required to obtain results with the BACTEC method ranged from 5 to 21 days (average 11.5 days). Results indicate that the radiometric method provides reportable results more frequently with time savings as compared to the conventional method.
Rattananupong, Thanapoom; Hiransuthikul, Narin; Lohsoonthorn, Vitool; Chuchottaworn, Charoen
Tuberculosis (TB) is common in Thailand. Delay in initiating tuberculosis treatment is a major public health problem. Delay in treatment can result in more severe diseases, risk for death, and greater risk of tuberculosis transmission in the community. We attempted to determine the duration from onset of TB symptoms to the date of first consultation (patient delay) and the factors associated with that delay at 10 tertiary level care hospitals in Thailand. All participants aged 18 years who were willing to participate were included in the study, which was conducted from January to December 2012. A structured questionnaire and medical records were used to collect data. One hundred ninety-nine TB patients were included in the study. The mean age of subjects was 48 years (SD = 15.9); 69.8% were male. The median duration from onset of symptoms to first medical consultation was 30 days. On multivariate analysis, living in an urban area (adjusted odds ratio = 2.81; 95% CI: 1.29-6.14) was an independent risk factor for the delay. Delay in seeking help is a common problem among TB patients in Thailand. At risk populations need to be educated on the importance of presenting for early medical consultation if they have symptoms of TB.
Mahato, Roshan Kumar; Koju, Rajendra
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
Kaushik, Amit; Singh, Urvashi B.; Porwal, Chhavi; Venugopal, Shwetha J.; Mohan, Anant; Krishnan, Anand; Goyal, Vinay; Banavaliker, Jayant N.
Background & objectives: Tuberculosis (TB) is a public health problem worldwide. Rapid and accurate diagnosis of tuberculosis is crucial to facilitate early treatment of infectious cases and to reduce its spread. The present study was aimed to evaluation of 16 kDa antigen as a serodiagnostic tool in pulmonary and extra-pulmonary tuberculosis patients in an effort to improve diagnostic algorithm for tuberculosis. Methods: In this study, 200 serum samples were collected from smear positive and culture confirmed pulmonary tuberculosis patients, 30 tubercular pleural effusions and 21 tubercular meningitis (TBM) patients. Serum samples from 36 healthy, age matched controls (hospital staff), along with 60 patients with non-tubercular respiratory diseases were also collected and evaluated. Humoral response (both IgG and IgA) was looked for 16 kDa antigen using indirect ELISA. Results: Sensitivity of detection in various categories of pulmonary TB patients ranged between 73.8 and 81.2 per cent. While in the extra-pulmonary TB samples the sensitivity was 42.8 per cent (TBM) and 63.3 per cent (tubercular pleural effusion). The test specificity in both the groups was high (94.7%). All of the non-disease controls were negative. Among non-tubercular disease controls, five patients gave a positive humoral response against 16 kDa. Interpretation & conclusions: Serodiagnostic tests for TB have always had drawbacks of suboptimal sensitivity and specificity. The antigen used in this study gave encouraging results in pulmonary TB only, while in extra-pulmonary TB (tubercular meningitis and tubercular pleural effusion), this has shown a limited role in terms of sensitivity. Further work is required to validate its role in serodiagnosis of TB especially extra-pulmonary TB. PMID:22771611
Hall, Ronald G.; Leff, Richard D.; Gumbo, Tawanda
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
Tang, Ming-xing; Zhang, Hong-qi; Wang, Yu-xiang; Guo, Chao-feng; Liu, Jin-yang
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
Ballester-Ferré, Maria Pilar; Martínez, Fernando; Garcia-Gimeno, Natalia; Mora, Francisco; Serra, Miguel A
Chronic hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. In the last 5 years, treatment for HCV infection has experienced a marked development. In 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. However, new side effects have been associated. We report the first case of an HCV infected patient treated for 12 wk with the combination of sofosbuvir/ledipasvir plus ribavirin who developed a miliary tuberculosis (TB) infection while on therapy. The patient was a 65-year-old woman, who referred malaise, asthenia, hyporexia, 7 kg weight loss, productive cough, evening fever and night sweats, right after finishing the treatment. The chest computed tomography-scan revealed a superior mediastinal widening secondary to numerous lymphadenopathies with extensive necrosis and bilateral diffuse lung miliary pattern with little subsequent bilateral pleural effusion, highly suggestive of lymph node tuberculosis with lung miliary spread. A bronchoscopy was performed and bronchial suction showed more than 50 acid-alcohol resistant bacillus per line. A Mycobacterium tuberculosis DNA was detected in blood by polymerase chain reaction, which confirmed the diagnosis of miliary tuberculosis. Some cases of TB infection have been identified with α-interferon-based therapy and with the triple therapy of pegylated interferon, ribavirin and boceprevir or telaprevir. However, significant infection has not been reported with sofosbuvir/ledipasvir plus ribavirin. We believe that the case is relevant to increase awareness of opportunistic infections and particularly TB infection. Although the international guidelines offer no recommendation regarding TB screening, we wonder whether it would be advisable to screen for opportunistic infections prior to the introduction of HCV therapy. PMID:28217253
Ballester-Ferré, Maria Pilar; Martínez, Fernando; Garcia-Gimeno, Natalia; Mora, Francisco; Serra, Miguel A
Chronic hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. In the last 5 years, treatment for HCV infection has experienced a marked development. In 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. However, new side effects have been associated. We report the first case of an HCV infected patient treated for 12 wk with the combination of sofosbuvir/ledipasvir plus ribavirin who developed a miliary tuberculosis (TB) infection while on therapy. The patient was a 65-year-old woman, who referred malaise, asthenia, hyporexia, 7 kg weight loss, productive cough, evening fever and night sweats, right after finishing the treatment. The chest computed tomography-scan revealed a superior mediastinal widening secondary to numerous lymphadenopathies with extensive necrosis and bilateral diffuse lung miliary pattern with little subsequent bilateral pleural effusion, highly suggestive of lymph node tuberculosis with lung miliary spread. A bronchoscopy was performed and bronchial suction showed more than 50 acid-alcohol resistant bacillus per line. A Mycobacterium tuberculosis DNA was detected in blood by polymerase chain reaction, which confirmed the diagnosis of miliary tuberculosis. Some cases of TB infection have been identified with α-interferon-based therapy and with the triple therapy of pegylated interferon, ribavirin and boceprevir or telaprevir. However, significant infection has not been reported with sofosbuvir/ledipasvir plus ribavirin. We believe that the case is relevant to increase awareness of opportunistic infections and particularly TB infection. Although the international guidelines offer no recommendation regarding TB screening, we wonder whether it would be advisable to screen for opportunistic infections prior to the introduction of HCV therapy.
Toloba, Y; Diallo, S; Maïga, Y; Sissoko, B F; Keïta, B
In order to describe the epidemio-clinical and evolutionary aspects of miliary tuberculosis (TB) in Mali, a retrospective study of 10 years (1 January 2000 to December 31, 2009) was conducted in the service of pneumo-phtisiology at the university hospital of point G. It concerned all patients with radiological images compatible with miliary TB, signs of bacillary impregnation, bacillus or not, treated with antituberculosis drugs. Of 3630 TB patients all forms recorded during the study period, 183 miliary were recorded (5%) including 117 men and 66 women. Young adults between 29-45 years were more represented (52%). The average diagnostic delay was 3.7 months. The symptomatology was dominated by the fever (100%), cough (90.1%) and asthenia (86.3%), anorexia (81.9%). The radiological images types of micronodular opacities were the most frequent in 147 cases (80.3%) against 36 cases of (19.7%) macronodular types. Bacteriological examination of sputum was negative in 139 patients (76%) and positive in 44 patients (24%). There was a statistically significant relationship between the presence of an excavation in Chest radiography and smear positivity (P<0.001). The clinical improvement observed (55.7%) depended on the time of the diagnosis (P<0.001). The serology HIV was positive at 29 patients on 124 tested. Also, in areas with high prevalence TB/HIV, any miliary fever in the absence of other obvious etiologies should undertake without delay TB proper treatment.
Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria
Objectives To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline. PMID:27708985
Botha, E; Den Boon, S; Verver, S; Dunbar, R; Lawrence, K-A; Bosman, M; Enarson, D A; Toms, I; Beyers, N
A study in 11 primary health care facilities in and around Cape Town determined the proportion of bacteriologically confirmed tuberculosis (TB) cases who did not start treatment (initial default) and identified reasons for it. Databases from centralised laboratories were compared with electronic TB treatment registers. Fourteen per cent (373/2758) of TB suspects were TB cases. Of the 58 (16%) initial defaulters, 14 (24%) died, while 26 (45%) could not be interviewed for address-related reasons. The 18 subjects who were interviewed indicated reasons for initial default that were (56%) or were not (44%) directly linked to services. High initial default rates require improvement in the quality of health services.
Bento, João; Duarte, Raquel; Brito, Maria Céu; Leite, Sónia; Lobato, Maria Rosário; do Carmo Caldeira, Maria; Carvalho, Aurora
Malabsorption of oral antimycobacterial drugs is a rare cause of treatment failure in tuberculosis (TB). Several predisposing comorbidities have been recognised. HIV infection is the most important risk factor referred in the literature. There are few reports about antimycobacterial drugs malabsorption, particularly in the absence of predisposing comorbidities. The authors present a clinical case of oral treatment failure in TB due to malabsorption; however, what caused the failure remained unclear. Possible causes of malabsorption are discussed under various sections. Purpose of this case report is to point to this rare situation that can easily go unnoticed unless a very high level of suspicion is present. PMID:22778380
Makori, L.; Gikera, M.; Wafula, J.; Chakaya, J.; Edginton, M. E.; Kumar, A. M. V.
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
Principi, Nicola; Galli, Luisa; Lancella, Laura; Tadolini, Marina; Migliori, Giovanni Battista; Villani, Alberto; Esposito, Susanna
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.
Silva, Denise Rossato; da Silva, Larissa Pozzebon; Dalcin, Paulo de Tarso Roth
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
Eyene, Juan; Momo, Juan Carlos; Biyé, Lucia; Esono, Teodoro; Ondó Mba Ayecab, Marcial; Benito, Agustín; Aparicio, Pilar
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
Fagundez, Gabriela; Perez-Freixo, Hugo; Eyene, Juan; Momo, Juan Carlos; Biyé, Lucia; Esono, Teodoro; Ondó Mba Ayecab, Marcial; Benito, Agustín; Aparicio, Pilar; Herrador, Zaida
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.
Holland, David P.; Sanders, Gillian D.; Hamilton, Carol D.; Stout, Jason E.
Rationale Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of “no treatment” used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries. PMID:21789248
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; Balasubramanian, V; Datta, Santanu
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).
Objective: Psychological distress is being recognized in individuals affected with many diseases since it affects quality of life (QOF) and has gained importance in the clinical settings. Psychological interventions and their effect on the treatment outcome have yielded encouraging results in many diseased conditions. Tuberculosis (TB) ranks as a deadly disease resulting in millions of deaths worldwide. However, the effect of TB on the psychological status of patients and interventions to improve treatment outcome is neglected, especially in underdeveloped and developing countries. Methods: Systematic review of research papers that published on the QOF in TB and the effect of psychological interventions on treatment outcome were conducted. Results: Tuberculosis patients experience high levels of stress and decreased QOF. In the Indian scenario, TB patients undergo immense psychological stress similar to what is reported in other locations. Psychological interventions renewed hope on life and adherence to medication and treatment outcomes. Such psychological interventions are not practiced in Indian clinical settings. Conclusion: There is an urgent need for both governmental and non-governmental organizations to devise strategies to include psychological interventions mandatory during TB treatments. In the absence of such interventions, the fight against TB in India will remain incomplete. PMID:27833578
Floyd, Katherine; Hutubessy, Raymond; Kliiman, Kai; Centis, Rosella; Khurieva, Nina; Jakobowiak, Wieslaw; Danilovits, Manfred; Peremitin, Genadi; Keshavjee, Salmaan; Migliori, Giovanni Battista
Evidence on the cost and cost-effectiveness of treatment of multidrug-resistant tuberculosis (MDR-TB) is limited, and no published data are available from former Soviet Union countries, where rates of MDR-TB are highest globally. We evaluated the cost and cost-effectiveness of MDR-TB treatment in Estonia and Russia (Tomsk Oblast), comparing cohorts enrolled on treatment according to World Health Organization (WHO) guidelines in 2001 and 2002 with cohorts treated in previous years. Costs were assessed from a health system perspective in 2003 US$; effects were measured as cures, deaths averted and disability-adjusted life-years (DALYs) averted. Cure rates when WHO guidelines were followed were 61% (90 out of 149) in Estonia and 76% (76 out of 100) in Tomsk Oblast, with a cost per patient treated of US$8,974 and US$10,088, respectively. Before WHO guidelines were followed, cure rates were 52% in Estonia and 15% in Tomsk Oblast; the cost per patient treated was US$4,729 and US$2,282, respectively. Drugs and hospitalisation accounted for 69-90% of total costs. The cost per DALY averted by treatment following WHO guidelines was US$579 (range US$297-US$902) in Estonia and US$429 (range US$302-US$546) in Tomsk Oblast. Treatment of patients with MDR-TB can be cost-effective, but requires substantial additional investment in tuberculosis control in priority countries.
Bark, C M; Dietze, R; Okwera, A; Quelapio, M I; Thiel, B A; Johnson, J L
During a recent Food and Drug Administration workshop on clinical trials to evaluate new TB drugs, questions were raised regarding the use of bacteriologic endpoints such as treatment failure and relapse as measures of improvement in health status and long term outcome after treatment. FDA scientists asked how patients' clinical signs and symptoms changed during therapy, noting that while such information is usually collected during clinical trials, it is not often reported. We analyzed data from an international phase 3 TB treatment trial that included systematic assessments of symptoms. The percentage of subjects with self-reported symptoms at baseline ranged from 30% for dyspnea to 81% for cough, with 51% reporting fever. During therapy, fever, sweats, and dyspnea decreased most rapidly, with near resolution by the end of therapy. Chest pain and cough resolved more slowly; 13% of subjects reported cough at six months. Symptom resolution during treatment did not differ between those who relapsed and those who did not. Among those with microbiological relapse, symptoms returned with significant increases in the proportion with fever, cough, and chest pain. At the time of relapse, cough was the most frequent symptom, occurring in 75% of subjects who relapsed but only 12% of those who did not. Our data support the continued use of bacteriologic endpoints based on sputum culture as surrogate measures of the relief of symptoms, improvement in health status and favorable long term treatment outcome in TB drug trials.
Rondags, Angelique; Himawan, Ari Budi; Metsemakers, Job Fm; Kristina, Tri Nur
One of the most serious problems for tuberculosis (TB) control is non-adherence to TB treatment. We studied the factors influencing non-adherence to TB treatment in Indonesia to inform TB treatment adherence strategies. We con- ducted semi-structured interviews with non-adherent patients and key informants in Jepara, Central Java, Indonesia. Three major themes were found in reasons for non-adherence to TB treatment: 1) knowledge about TB, 2) knowledge about TB treatment and 3) choosing and changing a health care treatment facility. Respondents had an inadequate knowledge about TB and its treatment. Feeling healthy and having financial problems were the most common reasons for TB treatment non-adherence. Respondents sought treatment from many different health care providers, and often changed the treatment facility location. TB treatment adherence might improve by providing better education about the disease and its treatment to those undergoing treatment. Providing information about where to receive treatment and that treatment is free could also improve compliance.
Veziris, N; Lounis, N; Chauffour, A; Truffot-Pernot, C; Jarlier, V
Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 x10(6) CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.
Veziris, N.; Lounis, N.; Chauffour, A.; Truffot-Pernot, C.; Jarlier, V.
Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 ×106 CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis. PMID:16189074
Brasil, Pedro Emmanuel Alvarenga Americano do; Braga, José Ueleres
The identification of factors that predict tuberculosis (TB) treatment default can help control this problem. The current study used a systematic review to investigate associations between TB treatment default and previously studied factors related to health services. Abstracts were searched in the MEDLINE and LILACS databases and in the bibliography of the full texts under evaluation. Studies were included if TB treatment default was evaluated by comparing two or more groups and data could be extracted. A total of 41 studies were included for combining data. It was possible to combine five exposures: "difficult access to health services"; "need for hospitalization"; "training or support for adherence"; "delay in initiating treatment"; "long wait before medical attendance". "Difficult access to health services", "training or support for adherence", and "need for hospitalization" were associated with TB treatment default. All exposures demonstrated heterogeneity, which was only explained in one. Publication bias was only detected for one exposure.
Volmink, J; Garner, P
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.
Chindelevitch, Leonid; Menzies, Nicolas A; Pretorius, Carel; Stover, John; Salomon, Joshua A; Cohen, Ted
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.
Tyagi, Sandeep; Ammerman, Nicole C; Li, Si-Yang; Adamson, John; Converse, Paul J; Swanson, Rosemary V; Almeida, Deepak V; Grosset, Jacques H
A key drug for the treatment of leprosy, clofazimine has recently been associated with highly effective and significantly shortened regimens for the treatment of multidrug-resistant tuberculosis (TB). Consequently, we hypothesized that clofazimine may also shorten the duration of treatment for drug-susceptible TB. We conducted a controlled trial in the mouse model of TB chemotherapy comparing the activity of the 6-mo standard regimen for TB treatment, i.e., 2 mo of daily rifampin, isoniazid, pyrazinamide, and ethambutol followed by 4 mo of rifampin and isoniazid, with a 4-mo clofazimine-containing regimen: 2 mo of daily rifampin, isoniazid, pyrazinamide, and clofazimine followed by 2 mo of rifampin, isoniazid, and clofazimine. Treatment efficacy was assessed on the basis of Mycobacterium tuberculosis colony counts in the lungs and spleens during treatment and on the proportion of mice with culture-positive relapse 6 mo after treatment cessation. No additive effect of clofazimine was observed after the first week of treatment, but, by the second week of treatment, the colony counts were significantly lower in the clofazimine-treated mice than in the mice receiving the standard regimen. Lung culture conversion was obtained after 3 and 5 mo in mice treated with the clofazimine-containing and standard regimens, respectively, and relapse-free cure was obtained after 3 and 6 mo of treatment with the clofazimine-containing and standard regimens, respectively. Thus, clofazimine is a promising anti-TB drug with the potential to shorten the duration of TB chemotherapy by at least half (3 mo vs. 6 mo) in the mouse model of TB.
Bekker, Adrie; Schaaf, Hendrik S.; Draper, Heather R.; Kriel, Magdalena; Hesseling, Anneke C.
Background Tuberculosis during pregnancy and treatment outcomes are poorly defined in high prevalence tuberculosis and HIV settings. Methods A prospective cohort study of pregnant and postpartum women identified to be routinely on antituberculosis treatment was conducted at Tygerberg Hospital, Cape Town, South Africa, from January 2011 through December 2011. Maternal tuberculosis disease spectrum and tuberculosis-exposed newborns were characterized by maternal HIV status. Maternal tuberculosis treatment outcomes were documented and a multivariable regression model identified predictors of unfavourable tuberculosis treatment outcomes. Infant outcomes were also described. Results Seventy-four women with tuberculosis, 53 (72%) HIV-infected, were consecutively enrolled; 35 (47%) were diagnosed at delivery or postpartum and 22 (30%) of women reported previous antituberculosis treatment. HIV-infected women were 5.67 times more likely to have extrapulmonary tuberculosis (95% CI 1.18–27.25, p = 0.03). All 5 maternal deaths were amongst HIV-infected women. Birth outcomes were available for 75 newborns (2 sets of twins, missing data for 1 stillbirth). Of the 75 newborns, 49 (65%) were premature and 44 (59%) were low birth weight (LBW; <2500 grams). All 6 infants who died and the 4 stillbirths were born to HIV-infected women. Unfavourable tuberculosis treatment outcomes were documented in 33/74 (45%) women. Unfavourable maternal tuberculosis outcome was associated with delivery of LBW infants (OR 3.83; 95% CI 1.40–10.53, p = 0.009). Conclusions A large number of pregnant women with tuberculosis presented at a provincial referral hospital. All maternal and infant deaths occurred in HIV-infected women and their newborns. Maternal tuberculosis treatment outcomes were poor. PMID:27812086
Nuermberger, Eric; Tyagi, Sandeep; Williams, Kathy N.; Rosenthal, Ian; Bishai, William R.; Grosset, Jacques H.
Rationale: Priorities for developing improved regimens for treatment of latent tuberculosis (TB) infection include (1) developing shorter and/or more intermittently administered regimens that are easier to supervise and (2) developing and evaluating regimens that are active against multidrug-resistant organisms. Objectives and Methods: By using a previously validated murine model that involves immunizing mice with Mycobacterium bovis bacillus Calmette-Guérin to augment host immunity before infection with virulent Mycobacterium tuberculosis, we evaluated new treatment regimens including rifapentine and moxifloxacin, and assessed the potential of the Mycobacterium leprae heat shock protein-65 DNA vaccine to augment the activity of moxifloxacin. Measurements: Quantitative spleen colony-forming unit counts, and the proportion of mice with culture-positive relapse after treatment, were determined. Main Results: Three-month, once-weekly regimens of rifapentine combined with either isoniazid or moxifloxacin were as active as daily isoniazid for 6–9 mo. Six-month daily combinations of moxifloxacin with pyrazinamide, ethionamide, or ethambutol were more active than pyrazinamide plus ethambutol, a regimen recommended for latent TB infection after exposure to multidrug-resistant TB. The combination of moxifloxacin with the experimental nitroimidazopyran PA-824 was especially active. Finally, the heat shock protein-65 DNA vaccine had no effect on colony-forming unit counts when given alone, but augmented the bactericidal activity of moxifloxacin. Conclusions: Together, these findings suggest that rifapentine, moxifloxacin, and, perhaps, therapeutic DNA vaccination have the potential to improve on the current treatment of latent TB infection. PMID:16151038
Lönnroth, Knut; Aung, Tin; Maung, Win; Kluge, Hans; Uplekar, Mukund
This article assesses whether social franchising of tuberculosis (TB) services in Myanmar has succeeded in providing quality treatment while ensuring equity in access and financial protection for poor patients. Newly diagnosed TB patients receiving treatment from private general practitioners (GPs) belonging to the franchise were identified. They were interviewed about social conditions, health seeking and health care costs at the time of starting treatment and again after 6 months follow-up. Routine data were used to ascertain clinical outcomes as well as to monitor trends in case notification. The franchisees contributed 2097 (21%) of the total 9951 total new sputum smear-positive pulmonary cases notified to the national TB programme in the study townships. The treatment success rate for new smear-positive cases was 84%, close to the World Health Organization target of 85% and similar to the treatment success of 81% in the national TB programme in Myanmar. People from the lower socio-economic groups represented 68% of the TB patients who access care in the franchise. Financial burden related to direct and indirect health care costs for tuberculosis was high, especially among the poor. Patients belonging to lower socio-economic groups incurred on average costs equivalent to 68% of annual per capita household income, with a median of 28%. However, 83% of all costs were incurred before starting treatment in the franchise, while 'shopping' for care. During treatment in the franchise, the cost of care was relatively low, corresponding to a median proportion of annual per capita income of 3% for people from lower socio-economic groups. This study shows that highly subsidized TB care delivered through a social franchise scheme in the private sector in Myanmar helped reach the poor with quality services, while partly protecting them from high health care expenditure. Extended outreach to others parts of the private sector may reduce diagnostic delay and patient costs
Lewin, Simon; Dick, Judy; Zwarenstein, Merrick; Lombard, Carl J.
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
Alavi, Seyed Mohammad; Salmanzadeh, Shokrollah; Bakhtiyariniya, Pejman; Albagi, Ali; Hemmatnia, Fatemeh; Alavi, Leila
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
Lenaerts, Anne M. J. A.; Chase, Sharon E.; Chmielewski, Alex J.; Cynamon, Michael H.
Besides direct bactericidal activity, long-term effectiveness is one of the most important features to consider when developing new drugs for chemotherapy. In this study, we evaluated the ability of rifapentine (RFP), in monotherapy and combination therapy, to completely eradicate a Mycobacterium tuberculosis infection and to prevent relapse posttreatment in a Swiss mouse model. The combination of RFP, isoniazid (INH), and pyrazinamide (PZA) administered daily resulted in an apparent clearance of M. tuberculosis organisms in the lungs and spleens of infected mice after 10 weeks of treatment. However, 3 months after the cessation of therapy, bacterial regrowth occurred in mice treated for a 12-week period, indicating a relapse of infection. In intermittent treatment regimens of RFP in combination with INH and PZA, sterilization was achieved when mice were treated two to five times per week for 9 weeks. Bacterial growth was still observed in the once-weekly treatment group. Our results show that mouse models can predict important parameters for new drugs. We stress the necessity for long-term posttreatment observation in animal models for the routine evaluation of new drugs for antituberculosis chemotherapy. PMID:10508006
Rodrigues, Ivaneide Leal Ataide; Monteiro, Larissa Lima; Pacheco, Régia Hevelline Barros; da Silva, Sílvio Eder Dias
This study aimed at analyzing the reasons that patients co-infected with tuberculosis and HIV leave the treatment of tuberculosis and to know the conduct of the health team toward that abandonment. The study, using a qualitative approach, performed semi-structured interviews on 45 professionals working at a referral health center in Pará state. Two units emerged based on the thematic analysis: patient-associated factors that make TB treatment adherence difficult; and service-associated factors that contribute to treatment abandonment. It was found that, in terms of the patients, that their low socioeconomic condition was the most common factor that led to abandonment. Other factors that led to this outcome included the adverse drug effects, the use of illegal drugs, and poor personal motivation. Regarding the service, issues related to the physical structure, working process organization and accessibility were also relevant to their non-adherence. Results show there is a need to change the practices performed at the health care services.
Folk, William R; Smith, Aaron; Song, Hailong; Chuang, Dennis; Cheng, Jianlin; Gu, Zezong; Sun, Grace
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.
Ketata, W; Rekik, W K; Ayadi, H; Kammoun, S
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.
Background Successful treatment of tuberculosis (TB) involves taking anti-tuberculosis drugs for at least six months. Poor adherence to treatment means patients remain infectious for longer, are more likely to relapse or succumb to tuberculosis and could result in treatment failure as well as foster emergence of drug resistant tuberculosis. Kenya is among countries with high tuberculosis burden globally. The purpose of this study was to determine the duration tuberculosis patients stay in treatment before defaulting and factors associated with default in Nairobi. Methods A Case-Control study; Cases were those who defaulted from treatment and Controls those who completed treatment course between January 2006 and March 2008. All (945) defaulters and 1033 randomly selected controls from among 5659 patients who completed treatment course in 30 high volume sites were enrolled. Secondary data was collected using a facility questionnaire. From among the enrolled, 120 cases and 154 controls were randomly selected and interviewed to obtain primary data not routinely collected. Data was analyzed using SPSS and Epi Info statistical software. Univariate and multivariate logistic regression analysis to determine association and Kaplan-Meier method to determine probability of staying in treatment over time were applied. Results Of 945 defaulters, 22.7% (215) and 20.4% (193) abandoned treatment within first and second months (intensive phase) of treatment respectively. Among 120 defaulters interviewed, 16.7% (20) attributed their default to ignorance, 12.5% (15) to traveling away from treatment site, 11.7% (14) to feeling better and 10.8% (13) to side-effects. On multivariate analysis, inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3), herbal medication use (OR 5.7; 95% CI 1.37-23.7), low income (OR 5.57, CI 1.07-30.0), alcohol abuse (OR 4.97; 95% CI 1.56-15.9), previous default (OR 2.33; 95% CI 1.16-4.68), co-infection with Human immune-deficient Virus (HIV) (OR 1
Pio, A.; Luelmo, F.; Kumaresan, J.; Spinaci, S.
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
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
Li, Lan; Xi, Yuliang; Ren, Fu
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
Field, Stephen K
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
García-García, Maria de Lourdes; Ponce-de-León, Alfredo; García-Sancho, Maria Cecilia; Ferreyra-Reyes, Leticia; Palacios-Martínez, Manuel; Fuentes, Javier; Kato-Maeda, Midori; Bobadilla, Miriam; Small, Peter; Sifuentes-Osornio, José
To describe the molecular epidemiology of tuberculosis (TB)-related deaths in a well-managed program in a low-HIV area, we analyzed data from a cohort of 454 pulmonary TB patients recruited between March 1995 and October 2000 in southern Mexico. Patients who were sputum acid-fast bacillus smear positive underwent clinical and mycobacteriologic evaluation (isolation, identification, drug-susceptibility testing, and IS6110-based genotyping and spoligotyping) and received treatment from the local directly observed treatment strategy (DOTS) program. After an average of 2.3 years of follow-up, death was higher for clustered cases (28.6 vs. 7%, p=0.01). Cox analysis revealed that TB-related mortality hazard ratios included treatment default (8.9), multidrug resistance (5.7), recently transmitted TB (4.1), weight loss (3.9), and having less than 6 years of formal education (2). In this community, TB is associated with high mortality rates. PMID:12453365
Chaskar, Priyanka; Rana, Geetika; Anuradha; Duggal, Nandini; Arora, Jyoti
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.
Domingos, Mirian Pereira; Caiaffa, Waleska Teixeira; Colosimo, Enrico Antônio
This non-concurrent cohort study aims to identify predictors of tuberculosis mortality in a large population database in Brazil. Tuberculosis, death, and TB/HIV cases were validated respectively from the tuberculosis surveillance (SINAN/TB), mortality (SIM), and SINAN/AIDS databases for a five-year period. Analysis included proportional hazard models with relative risk estimates. Out of 5,451 individuals reported with tuberculosis, 320 (5.9%) died (incidence and mortality rates of 98.6 and 12.2/100 thousand inhabitants, respectively). After adjustment, relative risk of dying from tuberculosis was 9.8 for individuals>50 years of age; 9.0 for TB/HIV co-infection; 3.0 for mixed TB clinical presentation; and 2.0 for treatment dropout. In the multivariate model, using cases with HIV/AIDS, all adjusted predictors lost significance except mixed clinical presentation (RR 1.9; 1.1-3.1). TB/HIV co-infection is an important predictor of TB mortality. However, among individuals without HIV/AIDS, mortality is still highly associated with older age, mixed clinical forms, and treatment dropout.
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
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
Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W
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.
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
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.
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
Elliott, E; Draper, H R; Baitsiwe, P; Claassens, M M
The Northern Cape Province has low cure rates (21%) for multidrug-resistant tuberculosis (TB). We audited the programme to identify factors affecting treatment outcomes. Cases admitted to two drug-resistant TB units from 2007 to 2009 had data extracted from clinical folders. Unfavourable treatment outcomes were found in 58% of the 272 cases. A multivariable regression analysis found that male sex was associated with unfavourable outcome (P = 0.009). Weight at diagnosis (P < 0.001) and oral drug adherence (P < 0.001) were also associated with an unfavourable outcome; however, injectable drug adherence was not (P = 0.395). Positive baseline smear and human immunodeficiency virus positive status were not associated with unfavourable outcome. Shorter, more patient-friendly regimens may go a long way to improving adherence and outcomes.
Munro, Salla A; Lewin, Simon A; Smith, Helen J; Engel, Mark E; Fretheim, Atle; Volmink, Jimmy
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
Chapple, Will; Katz, Alan Roy; Li, Dongmei
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
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
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
Grigorian, V A; Golovchenko, R N; Ustinov, A I
The case histories of 428 patients operated on for tuberculosis were analyzed. Three groups were identified. They were as follows: 1) 121 patients untreated with bactericidal drugs before surgery; 2) 247 patients treated less than 6 months before it; 3) 160 patients treated more than 6 months before surgery. Various complications due to resection of the lung were observed in 30 (7%) patients undergone surgery. They were 6.6, 6.8, and 7.5% in Groups 1, 2, and 3, respectively. A clinical effect was achieved in 99.8% of cases. The late outcomes of surgical intervention were studied within 1 to 10 years in 354 patients, including 102, 119, and 133 patients in Groups 1, 2, and 3, respectively. Progressive and recurrent tuberculosis was revealed in 7 (6.8%), 11 (9.2%), and 18 (13.5%), respectively. Thus, immediate and late outcomes of surgical treatment were not worse in patients with tuberculomas untreated with bactericidal drugs before surgery than in those who receive long-term therapy that substantially reduces the duration of therapy, which is a most important task of modern phthisiology. So patients should be operated on when they are found to have pulmonary tuberculomas without signs of a progressive tuberculous process.
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
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
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.
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
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
Maher, Dermot; Harries, Anthony D; Nachega, Jean B; Jaffar, Shabbar
The choice of research method relevant to the evaluation of delivery of a health intervention is not always straightforward. We use the evaluation of HIV and tuberculosis community treatment supporters in promoting adherence to treatment in Africa as a case study to illustrate the pros and cons of operational research and randomised controlled trials. The choice of this intervention for the case study reflects the importance of maximising the benefits of unprecedented efforts to scale-up treatments of these two epidemics. International policy supporting the role of community treatment supporters in tuberculosis is largely based on the findings of operational research studies. This reflects the advantages that operational research is less costly than randomised controlled trials, provides more rapid answers to policy questions, enables standard evaluation of the intervention in 'real life' conditions in several diverse settings and has in-built potential to influence policy and practice, because the research is conducted within health programmes. Recent evidence on the role of community treatment supporters in HIV is largely based on randomised trials. This reflects the advantages that randomised trials compared to operational research are more rigorous and generate a more convincing result. Operational research and randomised trials may be viewed as providing complementary findings to inform new policies and practice aimed at improving programme performance and patient outcomes. However, in practice, insufficient funds are likely to be made available for randomised trials to answer all the current research questions on delivery of programme interventions. In deciding on the type of research to evaluate a particular health intervention, dialogue is necessary with policy-makers to weigh up explicitly the trade-offs between research rigour and other factors such as cost, speed of implementation of research and speed of policy uptake and of change in programme practice.
Jayakumar, A; Savic, R M; Everett, C K; Benator, D; Alland, D; Heilig, C M; Weiner, M; Friedrich, S O; Martinson, N A; Kerrigan, A; Zamudio, C; Goldberg, S V; Whitworth, W C; Davis, J L; Nahid, P
The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity of rifapentine at daily doses of up to 20 mg/kg of body weight. Xpert was performed at weeks 0, 2, 4, 6, 8, and 12. Longitudinal CT data were modeled using a nonlinear mixed effects model in relation to rifapentine exposure (area under the concentration-time curve [AUC]). The rate of change of CT was higher in subjects receiving rifapentine than in subjects receiving standard-dose rifampin. Moreover, rifapentine exposure, but not assigned dose, was significantly associated with rate of change in CT (P = 0.02). The estimated increase in CT slope for every additional 100 μg · h/ml of rifapentine drug exposure (as measured by AUC) was 0.11 CT/week (95% confidence interval [CI], 0.05 to 0.17). Increasing rifapentine exposure is associated with a higher rate of change of Xpert CT, indicating faster clearance of Mycobacterium tuberculosis DNA. These data suggest that the quantitative outputs of the Xpert MTB/RIF assay may be useful as a dynamic measure of TB treatment response.
Jayakumar, A.; Savic, R. M.; Everett, C. K.; Benator, D.; Alland, D.; Heilig, C. M.; Weiner, M.; Friedrich, S. O.; Martinson, N. A.; Kerrigan, A.; Zamudio, C.; Goldberg, S. V.; Whitworth, W. C.; Davis, J. L.
The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity of rifapentine at daily doses of up to 20 mg/kg of body weight. Xpert was performed at weeks 0, 2, 4, 6, 8, and 12. Longitudinal CT data were modeled using a nonlinear mixed effects model in relation to rifapentine exposure (area under the concentration-time curve [AUC]). The rate of change of CT was higher in subjects receiving rifapentine than in subjects receiving standard-dose rifampin. Moreover, rifapentine exposure, but not assigned dose, was significantly associated with rate of change in CT (P = 0.02). The estimated increase in CT slope for every additional 100 μg · h/ml of rifapentine drug exposure (as measured by AUC) was 0.11 CT/week (95% confidence interval [CI], 0.05 to 0.17). Increasing rifapentine exposure is associated with a higher rate of change of Xpert CT, indicating faster clearance of Mycobacterium tuberculosis DNA. These data suggest that the quantitative outputs of the Xpert MTB/RIF assay may be useful as a dynamic measure of TB treatment response. PMID:27733634
Ko, Yousang; Shin, Jeong Hwan; Lee, Hyun-Kyung; Lee, Young Seok; Lee, Suh-Young; Park, So Young; Mo, Eun-Kyung; Kim, Changhwan
Background A sputum culture is the most reliable indicator of the infectiousness of pulmonary tuberculosis (PTB); however, a spontaneous sputum specimen may not be suitable. The aim of this study was to evaluate the infectious period in patients with non–drug-resistant (DR) PTB receiving adequate standard chemotherapy, using induced sputum (IS) specimens. Methods We evaluated the duration of infectiousness of PTB using a retrospective cohort design. Results Among the 35 patients with PTB, 22 were smear-positive. The rates of IS culture positivity from baseline to the sixth week of anti-tuberculosis medication in the smear-positive PTB group were 100%, 100%, 91%, 73%, 36%, and 18%, respectively. For smear-positive PTB cases, the median time of conversion to culture negativity was 35.0 days (range, 28.0–42.0 days). In the smear-negative PTB group (n=13), the weekly rates of positive IS culture were 100%, 77%, 39%, 8%, 0%, and 0%, respectively, and the median time to conversion to culture-negative was 21.0 days (range, 17.5–28.0 days). Conclusion The infectiousness of PTB, under adequate therapy, may persist longer than previously reported, even in patients with non-DR PTB. PMID:28119744
Orcau, Àngels; Millet, Joan-Pau; Ros, Miriam; Gil, Sonia; Caylà, Joan A.
Background The increase in immigration in Barcelona between 2000 and 2008 forced a reorganization of the control of tuberculosis (TB). TB clinical units (TBCU) were created and community health workers (CHW) were gradually included. Objective To understand trends in the incidence of TB among immigrants, their main characteristics and treatment compliance during the period 1991–2013. Design We conducted a cross-sectional population-based study of cases detected among immigrants by the Tuberculosis Program in Barcelona, Spain. Sociodemographic, clinical characteristics and risk factors were described. The annual incidence was calculated for various periods and geographical areas of origin. In the linear trend analysis, a p-value of <0.05 was considered statistically significant. Results We detected 3,284 cases. Incidence decreased from 144.8/100,000 inhabitants in 1991 to 53.4/100,000 in 2013. Individuals born in Pakistan-India-Bangladesh had the highest average annual incidence (675/100,000). In all, 2,156 cases (65.7%) were male. 2,272 (69.2%) had pulmonary TB, of which 48.2% were smear-positive. 33% of the cases (1,093) lived in the inner city. Contact tracing (CT) coverage in smear-positive individuals rose from 56.8% in 1991–1999 to 81.4% in 2000–2013 (p<0.01); this value was less than 50% in people from Africa and Eastern European countries. The case fatality rate was 3.6% overall and 9.8% among those born in high-income countries (p<0.01). The highest rate of treatment default (12.8%) was observed among cases from the Maghreb. The rate of successful treatment increased from 69.9% in 1991–1999 to 87.5% in 2000–2013 (p<0.01). Conclusion The incidence of TB in immigrants is decreasing in Barcelona. Organizational actions, such as incorporating CHWs and TBCUs, have been decisive for the observed improvements. PMID:27749904
Caylà, Joan A; Orcau, Angels
Tuberculosis (TB) is still a serious public health issue, even in large cities in developed countries. Control of this old disease is based on complicated programs that require completion of long treatments and contact tracing. In an accompanying research article published in BMC Public Health, Bothamley and colleagues found that areas with a ratio lower than one nurse per forty notifications had increased rates with respect to TB notifications, smear-positive cases, loss to follow-up and treatment abandonment across the UK. Furthermore, in these areas there was less opportunity for directly observed therapy, assistance with complex needs, educational outreach and new-entrant screening. In this commentary, we discuss the importance of improving organizational aspects and evaluating TB control programs. According to Bothamley and colleagues, a ratio of one nurse per forty notifications is an effective method of reducing the high TB incidences observed in London and in other cities in developed countries, or to maintain the decline in incidence in cities with lower incidences. It is crucial to evaluate TB programs every year to detect gaps early.
Guglielmetti, Lorenzo; Jaspard, Marie; Le Dû, Damien; Lachâtre, Marie; Marigot-Outtandy, Dhiba; Bernard, Christine; Veziris, Nicolas; Robert, Jérôme; Yazdanpanah, Yazdan; Caumes, Eric; Fréchet-Jachym, Mathilde
Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort.
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
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
Jagielski, T; Brzostek, A; van Belkum, A; Dziadek, J; Augustynowicz-Kopeć, E; Zwolska, Z
Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to the global control of the disease. The purpose of this study was to characterize MDR-TB patients from Poland and to determine the extent of MDR-TB disease attributable to recent transmission. The study included all 46 patients diagnosed with MDR-TB in Poland in 2004 and followed up for 6 years (until 2011). For each patient, sociodemographic and clinical characteristics, treatment outcomes, and bacteriological data were collected by the review of medical and laboratory records. Mycobacterium tuberculosis isolates from all patients were characterized using spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing, IS6110 restriction fragment length polymorphism (RFLP) analysis, and sequencing analysis of drug resistance-associated loci (katG, mabA-inhA, rpoβ, rpsL, and embB). The majority of patients were male (86.9%), 40-64 years of age (60.8%), with a history of TB treatment (84.8%), and producing smear-positive sputa (86.9%). Twenty-two (47.8%) patients suffered from concomitant diseases and 28 (60.8%) were alcohol abusers. Treatment outcome assessment revealed that 8 (17.4%) patients were cured or completed therapy, while 15 (32.6%) died of TB, 11 (23.9%) defaulted, 8 (17.4%) failed, and 1 (2.2%) was transferred and lost to follow-up. Upon genotyping, 10 (21.7%) isolates were allocated in four clusters. These were further subdivided by mutational profiling. Overall, in 6 (13%) patients, MDR-TB was a result of recent transmission. For 4 (8.7%) of these patients, a direct epidemiological link was established. The study shows that the transmission of MDR-TB occurs at a low rate in Poland. Of urgent need is the implementation of a policy of enforced treatment of MDR-TB patients in Poland.
Tola, Habteyes Hailu; Shojaeizadeh, Davoud; Garmaroudi, Gholamreza; Tol, Azar; Yekaninejad, Mir Saeed; Ejeta, Luche Tadesse; Kebede, Abebaw; Karimi, Mehrdad; Kassa, Desta
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: 1.17-7.75) and
Gärden, Bodil; Samarina, Arina; Stavchanskaya, Irina; Alsterlund, Rolf; Övregaard, Amanda; Taganova, Olga; Shpakovskaya, Ludmilla; Zjemkov, Vladimir; Ridell, Malin; Larsson, Lars-Olof
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.
Pienaar, Elsje; Cilfone, Nicholas A; Lin, Philana Ling; Dartois, Véronique; Mattila, Joshua T; Butler, J Russell; Flynn, JoAnne L; Kirschner, Denise E; Linderman, Jennifer J
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.
Pienaar, Elsje; Cilfone, Nicholas A.; Lin, Philana Ling; Dartois, Veronique; Mattila, Joshua T.; Butler, J. Russell; Flynn, JoAnne L.; Kirschner, Denise E.; Linderman, Jennifer J.
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. In this paper, 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. In conclusion, 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.
Mitnick, Carole D; White, Richard A; Lu, Chunling; Rodriguez, Carly A; Bayona, Jaime; Becerra, Mercedes C; Burgos, Marcos; Centis, Rosella; Cohen, Theodore; Cox, Helen; D'Ambrosio, Lia; Danilovitz, Manfred; Falzon, Dennis; Gelmanova, Irina Y; Gler, Maria T; Grinsdale, Jennifer A; Holtz, Timothy H; Keshavjee, Salmaan; Leimane, Vaira; Menzies, Dick; Migliori, Giovanni Battista; Milstein, Meredith B; Mishustin, Sergey P; Pagano, Marcello; Quelapio, Maria I; Shean, Karen; Shin, Sonya S; Tolman, Arielle W; van der Walt, Martha L; Van Deun, Armand; Viiklepp, Piret
Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
White, Richard A.; Lu, Chunling; Rodriguez, Carly A.; Bayona, Jaime; Becerra, Mercedes C.; Burgos, Marcos; Centis, Rosella; Cohen, Theodore; Cox, Helen; D'Ambrosio, Lia; Danilovitz, Manfred; Falzon, Dennis; Gelmanova, Irina Y.; Gler, Maria T.; Grinsdale, Jennifer A.; Holtz, Timothy H.; Keshavjee, Salmaan; Leimane, Vaira; Menzies, Dick; Milstein, Meredith B.; Mishustin, Sergey P.; Pagano, Marcello; Quelapio, Maria I.; Shean, Karen; Shin, Sonya S.; Tolman, Arielle W.; van der Walt, Martha L.; Van Deun, Armand; Viiklepp, Piret
Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection. We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference. Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34–0.42) for all patients and 0.33 (0.25–0.42) for HIV-co-infected patients. Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests. PMID:27587552
Mukhtar, Fatima; Butt, Zahid A
Purpose Pakistan is faced with an increasing prevalence of diabetes in addition to its existing high burden of tuberculosis (TB). Diabetes has a detrimental effect on treatment outcomes of patients with TB, which may hinder achieving the goals of the End-TB strategy by 2030. We conducted a prospective cohort study to determine difference between treatment outcomes among patients with diabetes and new pulmonary tuberculosis (PTB) and patients without diabetes and new PTB. This would help generate contextual and valid scientific evidence from a developing country like Pakistan with its unique interplay of sociocultural, economic and health system factors to inform policy and practice. Participants This paper outlines the baseline characteristics of 614 new cases of PTB, aged 15 years and older, which were followed up prospectively at 2nd, 5th and 6th months while on antituberculosis treatment and at 6 months after treatment completion. Findings to date We ascertained patients' diabetic status by conducting random and fasting blood glucose tests and their glycaemic control by determining glycosylated haemoglobin. Treatment outcomes were established using standardised definitions provided by WHO. The assessment of 614 respondents' diabetic status revealed that 113 (18%) were diabetic and 501 (82%) were non-diabetic. A greater proportion of patients with diabetes and PTB were illiterate (n=74/113, 65.5%) as compared to patients without diabetes and PTB (n=249/501, 50%) (p=0.035). More patients with diabetes and PTB gave a history of heart disease (n=14/113, 12%) and hypertension (n=26/113, 23%) as compared to patients without diabetes and PTB (n=2/501, 0.4% (heart disease) and n=13 501, 3% (hypertension)) (p<0.001). Unfavourable treatment outcome was more likely among patients with diabetes and PTB (n=23/93, 25%) as opposed to patients without diabetes and PTB (n=46/410, 11%) (p=0.001). Future plans We are negotiating with the government regarding funding for a
Rezgui, Amel; Fredj, Fatma Ben; Mzabi, Anis; Karmani, Monia; Laouani, Chadia
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.
Worley, Marylee V; Estrada, Sandy J
Bedaquiline is a diarylquinoline antitubercular drug with a novel mechanism of action against Mycobacterium tuberculosis. Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents in more than 40 years. Bedaquiline is indicated for the treatment of multidrug-resistant tuberculosis (MDR TB) in combination with at least three other antitubercular drugs when no other effective regimen is available. The recommended bedaquiline dosage is 400 mg orally once/day for 2 weeks followed by 200 mg orally 3 times/week for 22 weeks. Bedaquiline should be administered with food, which increases the bioavailability 2-fold. Bedaquiline is metabolized by cytochrome P450 isoenzyme 3A4 and is impacted by both inducers and inhibitors of this isoenzyme. Concentration-dependent bactericidal activity was observed in laboratory and murine studies. Accelerated approval was granted in the United States and European Union based on the results of two phase IIb clinical studies that used sputum culture clearance as a surrogate end point for clinical efficacy. These studies showed greater sputum culture clearance up to week 24 for the bedaquiline group compared with placebo. Common adverse events in clinical trials included nausea, arthralgia, and headache. Serious adverse events included elevated serum transaminase levels and rate-corrected QT-interval prolongation. Unexplained higher mortality was seen in patients receiving bedaquiline versus those receiving placebo. Bedaquiline is a novel agent with a unique mechanism of action and has the potential to meet a great need in patients with MDR TB who have no other treatment options. Due to safety concerns and limited clinical information, phase III trials are needed to fully determine its place in therapy.
Mpagama, Stellah G; Ndusilo, Norah; Stroup, Suzanne; Kumburu, Happiness; Peloquin, Charles A; Gratz, Jean; Houpt, Eric R; Kibiki, Gibson S; Heysell, Scott K
Little is known about plasma drug concentrations relative to quantitative susceptibility in patients with multidrug-resistant tuberculosis (MDR-TB). We previously described a TB drug activity (TDA) assay that determines the ratio of the time to detection of plasma-cocultured Mycobacterium tuberculosis versus control growth in a Bactec MGIT system. Here, we assess the activity of individual drugs in a typical MDR-TB regimen using the TDA assay. We also examined the relationship of the TDA to the drug concentration at 2 h (C2) and the MICs among adults on a MDR-TB regimen in Tanzania. These parameters were also compared to the treatment outcome of sputum culture conversion. Individually, moxifloxacin yielded superior TDA results versus ofloxacin, and only moxifloxacin and amikacin yielded TDAs equivalent to a -2-log killing. In the 25 patients enrolled on a regimen of kanamycin, levofloxacin, ethionamide, pyrazinamide, and cycloserine, the C2 values were found to be below the expected range for levofloxacin in 13 (52%) and kanamycin in 10 (40%). Three subjects with the lowest TDA result (<1.5, a finding indicative of poor killing) had significantly lower kanamycin C2/MIC ratios than subjects with a TDA of ≥1.5 (9.8 ± 8.7 versus 27.0 ± 19.1; P = 0.04). The mean TDAs were 2.52 ± 0.76 in subjects converting to negative in ≤2 months and 1.88 ± 0.57 in subjects converting to negative in >2 months (P = 0.08). In Tanzania, MDR-TB drug concentrations were frequently low, and a wide concentration/MIC range was observed that affected plasma drug activity ex vivo. An opportunity exists for pharmacokinetic optimization in current MDR-TB regimens, which may improve treatment response.
Hino, Paula; dos Santos, Claudia Benedita; Villa, Tereza Cristina Scatena; Muniz, Jordana Nogueira; Monroe, Aline Aparecida
This study presents a survey conducted among 132 Tuberculosis patients submitted to Supervised Treatment between 01/1998 and 12/1999, with a view to describing epidemiological aspects, according to the gender, (final) treatment result and HIV immunology result variables. The number of patients covered by Supervised Treatment rose from 19% to 30%. For each of these years, 64% and 71% of the patients were male, while 89% and 77% evolved towards cure. The rate of abandonment increased from 7% to 10%, while 4% and 10% of the patients died of Tuberculosis. The Tb/HIV co-infection represented 22% and 42% of the cases. The obtained results disclosed a tendency towards the gradual amplification of Supervised Treatment and its implementation implied.
... with facebook share with twitter share with linkedin Tuberculosis (TB) Tuberculosis (TB) is a contagious and often ... are drug resistant. Why Is the Study of Tuberculosis (TB) a Priority for NIAID? Tuberculosis is one ...
Ugarte-Gil, Cesar; Ruiz, Paulo; Zamudio, Carlos; Canaza, Luz; Otero, Larissa; Kruger, Hever; Seas, Carlos
Background Pulmonary tuberculosis (TB) persists an important contributor to the burden of diseases in developing countries. TB control success is based on the patient’s compliance to the treatment. Depressive disorders have been negatively associated with compliance of therapeutic schemes for chronic diseases. This study aimed to estimate the significance and magnitude of major depressive episode as a hazard factor for negative outcomes (NO), including abandon or death in patients receiving TB treatment. Methodology/Principal Findings A longitudinal study was conducted to evaluate the association of major depressive episode (MDE), as measured by a 5-item version of the Center for Epidemiological Studies Depression Scale (CES-D) with NO to TB treatment. Patients with confirmed TB were enrolled before the start of TB treatment. Baseline measurements included socio-demographic variables as well as the CES-D, which was also applied every month until the end of the treatment. Death and treatment default were assessed monthly. Survivor function (SF) for NO according to MDE status (CES-D≥6) at baseline (MDEb) was estimated. Cox’s Regression was performed for bivariate analyses as well as for the multivariate model. A total of 325 patients accepted to participate in the study, of which 34 where excluded for diagnosis of MDR-TB. NO was observed in 24 patients (8.2%); 109 (37%) presented MDEb. Statistically significant difference was found on the SF of patients with and without MDEb (0.85 vs. 0.96, p-value = 0.002). The hazard ratio for NO, controlled for age, sex, marital status and instruction level was 3.54 (95%CI 1.43–8.75; p-value = 0.006). Conclusion The presence of MDE at baseline is associated to NO of TB treatment. Targeting detection and treatment of MDE may improve TB treatment outcomes. PMID:23922728
Park, Cheol-Kyu; Shin, Hong-Joon; Kim, Yu-Il; Lim, Sung-Chul; Yoon, Jeong-Sun; Kim, Young-Su; Kim, Jung-Chul; Kwon, Yong-Soo
Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case-control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (< 2,000 US dollars/month, 88.1% vs. 68.4%, P = 0.015), absence of TB stigma (4.3% vs. 61.3%, P < 0.001), treatment by a non-pulmonologist (74.1% vs. 25.9%, P < 0.001), history of previous treatment (37.0% vs. 19.0%, P = 0.019), former defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078-265.365, P < 0.001), treatment by a non-pulmonologist (aOR: 14.567, 95% CI: 3.260-65.089, P < 0.001), former defaulters (aOR: 33.226, 95% CI: 2.658-415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249-22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default.
Crossa, Aldo; Kessler, Jason; Harris, Tiffany G.
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
Murhekar, M. V.; Kolappan, C.; Gopi, P. G.; Chakraborty, A. K.; Sehgal, S. C.
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
Chien, Jung-Yien; Chien, Shun-Tien; Chiu, Wei-Yih; Yu, Chong-Jen
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
Vidal, Júlia Souza; Silva, Marcus Tolentino; Sanchez, Mauro Niskier
Latent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.
Huang, Yi-Wen; Yang, Shun-Fa; Yeh, Yen-Po; Tsao, Thomas Chang-Yao; Tsao, Shih-Ming
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.
Lawal, I. O.; Grierson, D. S.; Afolayan, A. J.
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
Falzon, Dennis; Schünemann, Holger J; Harausz, Elizabeth; González-Angulo, Licé; Lienhardt, Christian; Jaramillo, Ernesto; Weyer, Karin
Antimicrobial resistance is a major global concern. Tuberculosis (TB) strains resistant to rifampicin and other TB medicines challenge patient survival and public health. The World Health Organization (WHO) has published treatment guidelines for drug-resistant TB since 1997 and last updated them in 2016 based on reviews of aggregated and individual patient data from published and unpublished studies. An international expert panel formulated recommendations following the GRADE approach. The new WHO guidelines recommend a standardised 9-12 months shorter treatment regimen as first choice in patients with multidrug- or rifampicin-resistant TB (MDR/RR-TB) strains not resistant to fluoroquinolones or second-line injectable agents; resistance to these two classes of core second-line medicines is rapidly detectable with molecular diagnostics also approved by WHO in 2016. The composition of longer regimens for patients ineligible for the shorter regimen was modified. A first-ever meta-analysis of individual paediatric patient data allowed treatment recommendations for childhood MDR/RR-TB to be made. Delamanid is now also recommended in patients aged 6-17 years. Partial lung resection is a recommended option in MDR/RR-TB care. The 2016 revision highlighted the continued shortage of high-quality evidence and implementation research, and reiterated the need for clinical trials and best-practice studies to improve MDR/RR-TB patient treatment outcomes and strengthen policy.
Slama, K; Tachfouti, N; Obtel, M; Nejjari, C
Interruption in tuberculosis (TB) treatment still remains the most important challenge for control of the disease. This study aimed to identify the determinants of TB treatment default in Fez, Morocco. A 1:2 pair-matched case-control study was carried out in the TB control units in Fez. Cases were defaulters to TB treatment and were matched by age and sex to non-defaulters (controls). Of the 320 patients (108 defaulters, 212 controls), 80.6% were male. The main reason for defaulting reported by patients was the sensation of being cured. Predictive factors for treatment default in the multivariate conditional logistic regression analysis, were: relapsed case (adjusted OR = 4.49; 95% Cl: 1.87-10.8), current smoking (aOR= 2.10; 95% Cl: 1.07-4.14), alcohol use (aOR = 2.92; 95% Cl: 1.04-8.19), being more than 30 minutes away from the health centre (aOR = 3.34; 95% Cl: 1.06-10.5) and perception of having received insufficient explanation about the disease (aOR = 2.87; 95% CI: 1.53-5.36). The rate of defaulting in Fez can be lowered through targeted and realistic measures.
Molecular Detection and Identification of Mycobacterium tuberculosis Complex and Four Clinically Important Nontuberculous Mycobacterial Species in Smear-Negative Clinical Samples by the GenoType Mycobacteria Direct Test ▿
Bicmen, Can; Gunduz, Ayriz T.; Coskun, Meral; Senol, Gunes; Cirak, A. Kadri; Ozsoz, Ayse
Although the sensitivity and specificity of nucleic acid amplification assays are high with smear-positive samples, the sensitivity with smear-negative and extrapulmonary samples for the diagnosis of tuberculosis in suspicious tuberculosis cases still remains to be investigated. This study evaluates the performance of the GenoType Mycobacteria Direct (GTMD) test for rapid molecular detection and identification of the Mycobacterium tuberculosis complex and four clinically important nontuberculous mycobacteria (M. avium, M. intracellulare, M. kansasii, and M. malmoense) in smear-negative samples. A total of 1,570 samples (1,103 bronchial aspiration, 127 sputum, and 340 extrapulmonary samples) were analyzed. When we evaluated the performance criteria in combination with a positive culture result and/or the clinical outcome of the patients, the overall sensitivity, specificity, and positive and negative predictive values were found to be 62.4, 99.5, 95.9, and 93.9%, respectively, whereas they were 63.2, 99.4, 95.7, and 92.8%, respectively, for pulmonary samples and 52.9, 100, 100, and 97.6%, respectively, for extrapulmonary samples. Among the culture-positive samples which had Mycobacterium species detectable by the GTMD test, three samples were identified to be M. intracellulare and one sample was identified to be M. avium. However, five M. intracellulare samples and an M. kansasii sample could not be identified by the molecular test and were found to be negative. The GTMD test has been a reliable, practical, and easy tool for rapid diagnosis of smear-negative pulmonary and extrapulmonary tuberculosis so that effective precautions may be taken and appropriate treatment may be initiated. However, the low sensitivity level should be considered in the differentiation of suspected tuberculosis and some other clinical condition until the culture result is found to be negative and a true picture of the clinical outcome is obtained. PMID:21653780
Webb Mazinyo, Ernesha; Kim, Lindsay; Masuku, Sikhethiwe; Lancaster, Joey L.; Odendaal, Ronel; Uys, Margot; Podewils, Laura Jean; Van der Walt, Martie L.
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
Basu, Sanjay; Galvani, Alison P
The evolution of Mycobacterium tuberculosis presents several challenges for public health. HIV and resistance to antimycobacterial medications have evolutionary implications for how Mycobacterium tuberculosis will evolve, as these factors influence the host environment and transmission dynamics of tuberculosis strains. We present an evolutionary invasion analysis of tuberculosis that characterizes the direction of tuberculosis evolution in the context of different natural and human-driven selective pressures, including changes in tuberculosis treatment and HIV prevalence. We find that the evolution of tuberculosis virulence can be affected by treatment success rates, the relative transmissibility of emerging strains, the rate of reactivation from latency among hosts, and the life expectancy of hosts. We find that the virulence of tuberculosis strains may also increase as a consequence of rising HIV prevalence, requiring faster case detection strategies in areas where the epidemics of HIV and tuberculosis collide.
Garrido, Marlucia da Silva; Penna, Maria Lucia; Perez-Porcuna, Tomàs M.; de Souza, Alexandra Brito; Marreiro, Leni da Silva; Albuquerque, Bernardino Claudio; Martínez-Espinosa, Flor Ernestina; Bührer-Sékula, Samira
Setting Treatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains. Objective This study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions. Design Observational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as ‘cases’ and those completing treatment as ‘controls’. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls. Results Treatment default was observed to be associated to previous default (aOR 3.20; p<0.001), HIV positivity (aOR 1.62; p<0.001), alcoholism (aOR 1.51; p<0.001), low education level (aOR 1.35; p<0.001) and other co-morbidities (aOR 1.31; p = 0.05). Older patients (aOR 0.98; p = 0.001) and DOT (aOR 0,72; p<0.01) were considered as protective factor for default. Conclusions Associated factors should be considered in addressing care and policy actions to tuberculosis control. Information on disease and treatment should be intensified and appropriate to the level of education of the population, in order to promote adherence to treatment and counter the spread of multidrug resistance to anti-TB drugs. PMID:22720052
Cohen, Ted; Zignol, Matteo; Nyakan, Edwin; Hedt-Gauthier, Bethany L.; Gardner, Adrian; Kamle, Lydia; Injera, Wilfred; Carter, E. Jane
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
Báez-Saldaña, Renata; Delgado-Sánchez, Guadalupe; García-García, Lourdes; Cruz-Hervert, Luis Pablo; Montesinos-Castillo, Marlene; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Yanes-Lane, Mercedes; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo
Background Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. Objective To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. Materials and Methods We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. Results Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15–2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08–6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38–45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00–10.84). All the models were adjusted for socio-demographic and clinical variables. Conclusions The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal
Liu, Qin; Abba, Katharine; Alejandria, Marissa M; Sinclair, David; Balanag, Vincent M; Lansang, Mary Ann D
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
Reis-Santos, Bárbara; Gomes, Teresa; Locatelli, Rodrigo; de Oliveira, Elizabete R.; Sanchez, Mauro N.; Horta, Bernardo L.; Riley, Lee W.; Maciel, Ethel L.
Background The impact of non-communicable diseases on tuberculosis incidence has received significant attention. It has been suggested that the risk of tuberculosis is higher among subjects with diabetes and these subjects also has poor TB treatment outcomes.This study was aimed at assessing the socio-demographic and clinical factors that may influence different outcome of TB in patients with DM (TB-DM) identified in the Brazilian national database from 2001 to 2011. Methods TB-DM cases reported in the Brazilian information system were identified and compared.Covariates associated with the outcomes of interest (cure, default, deaths, and development of TB MDR) were included in a hierarchical regression model. Results TB-DM cases increased from 380/100,000/year in 2001 to 6,150/100,000/year in 2011. Some of the main associations found are pointed. The odds of default was higher among those in the age group 20–39 years (OR = 2.07, 95%CI 1.32–3.24); alcoholics (OR = 2.17, 95%CI 1.86–2.54), and HIV/AIDS (OR = 2.16, 95%CI 1.70–2.74);positive monitoring smear (OR = 1.94, 95%CI 1.55–2.43); prior default (OR = 5.41, 95%CI 4.47–6.54), and unknown type of treatment (OR = 3.33, 95%CI 1.54–7.22). The odds of death was greater for subjects ≥60 years old (OR = 2.74, 95%CI 1.74–4.29); institutionalized in shelter (OR = 2.69, 95%CI 1.07–6.77); alcoholics (OR = 2.70, 95%CI 2.27–3.22); HIV/AIDS (OR = 2.87, 95%CI 2.13–3.86); pulmonary+extrapulmonary TB (OR = 2.49, 95%CI 1.79–3.46); with unknown type of treatment (OR = 14.12, 95%CI 7.04–28.32).Development of MDR TB was more related to relapse (OR = 9.60, 95%CI 6.07–15.14);previous default (OR = 17.13, 95%CI 9.58–30.63); and transfer of treatment center (OR = 7.87, 95%CI 4.74–13.07). Conclusions Older subjects and those with comorbidities and with a previous treatment of TB had poorest outcomes. TB control program in Brazil will need to expand
Active tuberculosis (TB) has a greater burden of TB bacilli than latent TB and acts as an infection source for contacts. Latent tuberculosis infection (LTBI) is the state in which humans are infected with Mycobacterium tuberculosis without any clinical symptoms, radiological abnormality, or microbiological evidence. TB is transmissible by respiratory droplet nucleus of 1–5 µm in diameter, containing 1–10 TB bacilli. TB transmission is affected by the strength of the infectious source, infectiousness of TB bacilli, immunoresistance of the host, environmental stresses, and biosocial factors. Infection controls to reduce TB transmission consist of managerial activities, administrative control, engineering control, environmental control, and personal protective equipment provision. However, diagnosis and treatment for LTBI as a national TB control program is an important strategy on the precondition that active TB is not missed. Therefore, more concrete evidences for LTBI management based on clinical and public perspectives are needed. PMID:27790271
Wobeser, W; Yuan, L; Naus, M
BACKGROUND: Completion of treatment of active cases of tuberculosis (TB) is the most important priority of TB control programs. This study was carried out to assess treatment completion for active cases of pulmonary TB in Toronto. METHODS: Consecutive cases of culture-proven pulmonary TB were obtained from the microbiology laboratories of 5 university-affiliated tertiary care centres in Toronto in 1992/93. A standard data-collection tool was used to abstract information from inpatient and outpatient charts. For patients who were transferred to other treatment centres or lost to follow-up, the local health unit was contacted for information about treatment completion. If incomplete information was obtained from these sources, data from the provincial Reportable Disease Information System were also reviewed. The main outcome analysed was treatment outcome, with cases classified as completed (record of treatment completion noted), transferred (patient transferred to another centre but no treatment results available), defaulted (record of defaulting in patient chart but no record of treatment completion elsewhere, or patient still receiving treatment more than 15 months after diagnosis) or dead (patient died before treatment completion). RESULTS: Of the 145 patients 84 (58%) completed treatment, 25 (17%) died, 22 (15%) defaulted and 14 (10%) were transferred. The corresponding values for the 22 patients with HIV coinfection were 6 (27%), 5 (23%), 8 (36%) and 3 (14%). Independent predictors of failure to complete treatment were injection drug use (adjusted odds ratio [OR] 5.7, 95% confidence interval [CI] 1.5 to 22.0), HIV infection (adjusted OR 4.6, 95% CI 1.4 to 14.7) and adverse drug reaction (adjusted OR 2.9, 95% CI 1.1 to 7.9). Independent predictors of death included age more than 50 years (adjusted OR 16.7, 95% CI 2.6 to 105.1), HIV infection (adjusted OR 16.1, 95% CI 3.9 to 66.4), immunosuppressive therapy (adjusted OR 8.0, 95% CI 1.9 to 34.4) and infection with
Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India
Singhal, Ritu; Reynolds, Paul R.; Marola, Jamie L.; Epperson, L. Elaine; Arora, Jyoti; Sarin, Rohit; Strong, Michael
Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in the gyrA and gyrB genes of Mycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in the gyrA and gyrB genes of acid-fast bacillus (AFB) smear-positive sediments or of M. tuberculosis isolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of the gyrA and gyrB genes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in the gyrA genes of 25 strains, while no mutations were observed in the gyrB genes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. The gyrA mutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis. PMID:27335153
García-Elorriaga, Guadalupe; Carrillo-Montes, Guadalupe; Mendoza-Aguilar, Melby; González-Bonilla, César
This study compared the frequency of the genetic polymorphisms of tumor necrosis factor (TNF) in pulmonary tuberculosis without and with response to treatment. We carried out an observational, prospective, comparative study. Three groups were studied: healthy subjects, responders, and non-responders to directly observed treatment short-course. We took a peripheral blood sample for identification of polymorphic genotypes TNF -308G/A and lymphotoxin A (LTA) +252G/A by polymerase chain reaction, and their later digestion with the Nco1 restriction enzyme. We studied a total of 138 subjects: 42 (non-responders) and 48 in each of the remaining groups. Healthy subjects had significantly high frequency of the LTA +252A allele compared to groups of patients and could be related with protection from the disease. Patients had higher frequency of the non-polymorphic allele LTA +252G than healthy subjects. With regard to LTA +252G/A genotype, we did find a significant difference with a greater frequency in the group of patients. The LTA +252G/A genotype was associated with impaired response to treatment.
Farnia, Parissa; Mohammadi, Foroazan; Mirsaedi, Mehdi; Zarife, Abolhasan Zia; Tabatabee, Javad; Bahadori, Katayoon; Bahadori, Muslem; Masjedi, Mohammad Reza; Velayati, Ali Akbar
By oxidation-reduction assay, the viability of Mycobacterium tuberculosis in sputum specimens was evaluated. The technique is based on the Alamar Blue and Malachite Green dyes, which change their color in response to M. tuberculosis growth. The method is simple, permits visual reading of results, and is applicable for laboratories with limited resources. PMID:15243106
Votintseva, Antonina A; Bradley, Phelim; Pankhurst, Louise; Del Ojo Elias, Carlos; Loose, Matthew; Nilgiriwala, Kayzad; Chatterjee, Anirvan; Smith, E Grace; Sanderson, Nicolas; Walker, Timothy M; Morgan, Marcus R; Wyllie, David H; Walker, A Sarah; Peto, Tim E A; Crook, Derrick W; Iqbal, Zamin
Routine full characterization of Mycobacterium tuberculosis (TB) is culture-based, taking many weeks. Whole-genome sequencing (WGS) can generate antibiotic susceptibility profiles to inform treatment, augmented with strain information for global surveillance; such data could be transformative if provided at or near point of care.We demonstrate a low-cost DNA extraction method for TB WGS direct from patient samples. We initially evaluated the method using the Illumina MiSeq sequencer (40 smear-positive respiratory samples, obtained after routine clinical testing, and 27 matched liquid cultures). M. tuberculosis was identified in all 39 samples from which DNA was successfully extracted. Sufficient data for antibiotic susceptibility prediction was obtained from 24 (62%) samples; all results were concordant with reference laboratory phenotypes. Phylogenetic placement was concordant between direct and cultured samples. Using an Illumina MiSeq/MiniSeq the workflow from patient sample to results can be completed in 44/16 hours at a reagent cost of £96/£198 per sample.We then employed a non-specific PCR-based library preparation method for sequencing on an Oxford Nanopore Technologies MinION sequencer. We applied this to cultured Mycobacterium bovis BCG strain (BCG), and to combined culture-negative sputum DNA and BCG DNA. For flowcell version R9.4, the estimated turnaround time from patient to identification of BCG, detection of pyrazinamide resistance, and phylogenetic placement was 7.5 hours, with full susceptibility results 5 hours later. Antibiotic susceptibility predictions were fully concordant. A critical advantage of the MinION is the ability to continue sequencing until sufficient coverage is obtained, providing a potential solution to the problem of variable amounts of M. tuberculosis in direct samples.
Ranjbar, Reza; Hafezi-Moghadam, Mohammad Sadegh
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
Turpie, I D
This is a description of a tuberculosis treatment programme in a country at war where security and the absence of order pose problems to health care delivery. It is also a description of an epidemic of tuberculosis where treatment and diagnosis are difficult and the methods used have changed little in many years. More international pressure is needed.
Migliori, G. B.; Ambrosetti, M.; Besozzi, G.; Farris, B.; Nutini, S.; Saini, L.; Casali, L.; Nardini, S.; Bugiani, M.; Neri, M.; Raviglione, M. C.
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
Rockwood, Neesha; Wojno, Justyna; Ghebrekristos, Yonas; Nicol, Mark P; Meintjes, Graeme; Wilkinson, Robert J
The utility of line probe assay (Genotype MTBDRplus) performed directly on 2-month sputa to monitor tuberculosis treatment response is unknown. We assessed if direct testing of 2-month sputa with MTBDRplus can predict 2-month culture conversion and long-term treatment outcome. Xpert® MTB/RIF-confirmed rifampicin-susceptible tuberculosis cases were recruited at tuberculosis diagnosis and followed up at 2 and 5-6 months. MTBDRplus was performed directly on 2-month sputa and on all positive culture isolates at 2 and 5-6 months. We also investigated the association of a positive direct MTBDRplus at 2 months with subsequent unsuccessful tuberculosis treatment outcome (failure/death during treatment or subsequent disease recurrence).279 cases (62% HIV-1 co-infected) were recruited. Direct MTBDRplus at 2 months had a sensitivity of 78%(95%CI 65-87) and specificity of 80%(95%CI 74-84) to predict culture positivity at 2 months with a high negative predictive value of 93%(95%CI 89-96). Inconclusive genotypic susceptibility for both rifampicin and isoniazid were seen in 26% of MTDDRplus tests performed directly on sputum. When compared to a reference of MTBDRplus performed on positive cultures, the false positive resistance rate for direct testing of MTBDRplus on sputa was 4% for rifampicin and 2% for isoniazid. Whilst a positive 2-month smear was not significantly associated with an unsuccessful treatment outcome, (aOR 2.69, 95% CI 0.88-8.21), a positive direct MTBDRplus at 2 months was associated with an unsuccessful outcome (aOR 2.87, 95%CI 1.11-7.42). There is moderate utility of direct 2-month MTBDRplus to predict culture conversion at 2 months and also to predict an unfavorable outcome.
Dangisso, Mesay Hailu; Datiko, Daniel Gemechu; Lindtjørn, Bernt
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
Shahrezaei, Marzieh; Maracy, Mohammad Reza; Farid, Fariba
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
Hossain, Sarder Tanzir; Isaakidis, Petros; Sagili, Karuna D.; Islam, Shayla; Islam, Md Akramul; Shewade, Hemant Deepak; Kamal, S. M. Mostofa; Husain, Ashaque
Objectives To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition. Methods This was a retrospective cohort study involving record review. Presumptive MDR-TB patients from peripheral microscopy centres serving 60% of the total population of Bangladesh were included in the study. Attrition and turnaround time for MDR-TB diagnosis by Xpert MTB/RIF and treatment initiation were calculated between July 2012 and June 2014. Results Of 836 presumptive MDR-TB patients referred from 398 peripheral microscopy centres, 161 MDR-TB patients were diagnosed. The number of diagnosed MDR-TB patients was less than country estimates of MDR-TB patients (2000 cases) during the study period. Among those referred, pre-diagnosis and pre-treatment attrition was 17% and 21% respectively. Median turnaround time for MDR-TB testing, result receipt and treatment initiation was four, zero and five days respectively. Farmers (RR=2.3, p=0.01) and daily wage laborers (RR=2.1, p=0.04) had twice the risk of having pre-diagnosis attrition. Poor record-keeping and unreliable upkeep of presumptive MDR-TB patient databases were identified as challenges at the peripheral microscopy centres. Conclusion There was a low proportion of pre-diagnosis and pre-treatment attrition in patients with presumptive and confirmed MDR-TB under programmatic conditions. However, the recording and reporting system did not detect all presumptive MDR-TB patients, highlighting the need to improve the system in order to prevent morbidity, mortality and transmission of MDR-TB in the community. PMID:26110273
Pienaar, Elsje; Cilfone, Nicholas A.; Lin, Philana Ling; ...
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.more » In this paper, 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. In conclusion, 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.« less
Pinheiro, Rejane Sobrino; Andrade, Vanusa de Lemos; Oliveira, Gisele Pinto de
This study aimed to analyze underreporting of tuberculosis (TB) cases in the Information System on Notifiable Diseases (SINAN), based on the following data sources: Mortality Information System (SIM), Registry and Follow-up Book for TB Case Treatment (LPATB), and Laboratory Registry Book (LRLAB). Probabilistic record linkage was used between the SIM (2007-2008) and SINAN (2002-2008). A search was conducted in LPATB and LRLAB (2007-2008) for cases not recorded in SINAN. There were 125 deaths, of which 44.8% were not recorded in SINAN. In LPATB, 58 cases (5.1%) were in treatment and were not reported in SINAN. LRLAB showed 32 smear-positive cases not reported to SINAN and without treatment, representing primary default. Addition of the retrieved cases, led to a 14.6% increase in the incidence rate in 2007 and 11.6% in 2008. Underreporting of deaths from or with TB in the Mortality Information System and primary default revealed difficulties in access to adequate and timely treatment, calling for rethinking of strategies to detect cases for timely treatment.
Ito, K L
A majority of Vietnamese refugees entering the United States test positive for inactive tuberculosis (TB). In asymptomatic conditions like inactive TB, it is often difficult to obtain compliance with medical treatment. The clinical encounter has been analyzed as a form of symbolic action between doctor and patient critical to patient trust and compliance. However, it is equally, if not more, important to understand the health culture of patients, that is, the broader sociocultural context of the patient within which his or her illness is interpreted and understood. In this article I look at health culture elements that influence compliance and noncompliance by Vietnamese American clients with courses of preventive drug therapy for inactive TB. Key factors in compliance are: (1) cultural interpretations of the therapy's side effects as "hot"; (2) the role of family members and peers; and (3) community perceptions of the drug treatment. Culturally incongruent elements of the clinical encounter and the funding of community-based organizations for health education also are examined.
Yang, Wei-Teng; Gounder, Celine R.; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N.; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita
Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men. PMID:24876956
Yang, Wei-Teng; Gounder, Celine R; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita
Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men.
Scott, C; Gardiner, E; de Lucia, A
Simple, quality-assured, child-friendly formulations of existing first-line anti-tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products.
Capone, Domenico; Mafort, Thiago; Mogami, Roberto; Rodrigues, Rosana de Souza; Menna Barreto, Miriam
Objectives. To evaluate tomographic changes in pulmonary tuberculosis (TB), degree of agreement among three radiologists regarding tomographic diagnoses, and sequelae following treatment. Methods. Cross-sectional and descriptive study of 74 TB patients confirmed by sputum culture and chest computed tomography before (CT1) and 6 months after (CT2) drug therapy. Results were performed by three radiologists blinded to clinical and laboratory results. Results. Main findings in CT1 included nodules indicating the presence of a tree-in-bud pattern in 93% of cases, ill-defined nodules in 84% of cases, consolidation in 77% of cases, architectural distortion in 71% of cases, cavitary lesions in 62% of cases, and ground glass opacities in 37% of cases. Airway involvement, characterized by increased thickness and dilatation of the bronchial walls, occurred in 93% of cases. Pleural involvement occurred in 54%. There was an agreement on active TB among the three radiologists in 85% of cases. The results in CT2 indicated the presence of architectural distortion in 91% of cases and cylindrical bronchiectasis in 86%. Conclusions. The study established a tomographic pattern for diagnosis of active TB characterized by the presence of airway nodules, consolidation, architectural distortion, and cavitary lesions, and an almost complete degree of agreement (Kappa) was observed among the radiologists (0.85). CT after treatment assists in defining the cure. PMID:28261498
Sabran, Siti Fatimah; Mohamed, Maryati; Abu Bakar, Mohd Fadzelly
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
Bojorquez, Ietza; Salazar, Irais; Garfein, Richard S; Cerecer, Paris; Rodwell, Timothy C
Directly observed therapy (DOT) is a cornerstone of tuberculosis (TB) control. DOT has been criticised as paternalistic, but it has also been argued that the interaction with healthcare workers (HWs) can be a source of support for patients. We explored the experience of patients in antituberculosis treatment, with the aim of understanding the balance between surveillance and support from the recipient's point of view. We interviewed 27 patients in Tijuana, Mexico, employing narrative analysis to understand how participants made sense of their illness and their experience of DOT. We found a core narrative of biographic disruption and self-reconstruction, in which HWs helped participants to attribute a less negative meaning to TB. Interviewees accepted DOT's as necessary for other people to avoid treatment abandonment, but felt that in their case it was unnecessary. Only a few felt that DOT represented mistrust on the part of the HWs. We conclude that DOT can be a source of support when it is enacted in a patient-centred way. We discuss whether participants' lack of criticism of DOT is a case of adaptive preference, in the context of a power differential between patient and health system.
Sharma, Surendra K.; Mohan, Alladi; Chauhan, L.S.; Narain, J.P.; Kumar, P.; Behera, D.; Sachdeva, K.S.; Kumar, Ashok
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
Elmadhooun, Wadie M.; Salah, Elmuntasir Taha; Noor, Sufian K.; Bushara, Sarra O.; Ahmed, Ekhlas O.; Mustafa, Hamdan; Sulaiman, Amel A.; Ahmed, Mohamed H.
Introduction: Tuberculosis (TB) is a significant cause of morbidity and mortality among children. The vague symptoms, the uncertain diagnostic tests and lack of adequate awareness among families all contributed in masking the actual prevalence of the disease. The objective of this study was to describe the epidemiology of childhood TB in River Nile State (RNS), North Sudan. Methods: All registered cases of TB aged 15 years and below, at the 13 management units in RNS during 3 years, 2011–2013 were included. The records included epidemiological, clinical, and microbiological data. Results: Out of the 1221 total TB notified cases, children were 187 (15.3%); almost equally distributed across the 3 years of the study period. Males were 56.7%. Most of the cases (89.9%) were newly diagnosed; among them, pulmonary TB (PTB) constituted 61.5%. Sputum specimen was tested in 59.4% (111/187) of cases, and only 15.3% (17/111) of specimens were sputum smear positive for new cases. The cure rate was (76.5%), and the treatment success rate was (88.2%). The death rate was 6.1% among PTB cases and 5.6% among extra-pulmonary cases. All the 20 (10.7%) children tested for HIV were negative. Conclusion: TB is under-reported in RNS and treatment outcomes are sub-optimal. Strategies to identify the active case-detection among children are recommended. PMID:28250686
Baig, Zahid Farooq; Raja, Khalid Mahmood; Abbas, Fahad
Vasculitis (Wegeners Granulomatosis and Microscopic Polyangiitis) and Tuberculosis share many features including constitutional symptoms and respiratory tract involvement. The presence of kidney involvement with new onset azotaemia and active urine sediment support the diagnosis of vasculitis. We describe two cases that were diagnosed to be suffering from tuberculosis and placed on anti-tuberculosis therapy. On further workup they were found to be suffering from pauci- immune glomerulonephritis and recovered well with treatment.
Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G.; Swaminathan, Soumya; Gumbo, Tawanda
Background. No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. Methods. We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix. We then used the hollow fiber system (HFS) model of intracellular tuberculosis to identify optimal dose schedules and exposures of moxifloxacin and linezolid in combination. We mimicked pediatric half-lives and concentrations achieved by each drug. We sampled the peripheral compartment on days 0, 7, 14, 21, and 28 for Mtb quantification, and compared the slope of microbial kill of Mtb by these regimens to the standard regimen of isoniazid, rifampin, and pyrazinamide, based on exponential decline regression. Results. The full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 ± 0.66 for linezolid and 3.80 ± 1.34 hours for moxifloxacin. The kill rate constant was 0.060 ± 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 ± 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively. Conclusions. We identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children. PMID:27742639
Manosuthi, Weerawat; Kawkitinarong, Kamon; Suwanpimolkul, Gompol; Chokbumrungsuk, Channarong; Jirawattanapisal, Thidaporn; Ruxrungtham, Kiat; Akksilp, Somsak
Tuberculosis (TB) is a public health problem in many large cities. We retrospectively studied the clinical characteristics and treatment outcomes of patients with active TB at 6 hospitals in Bangkok and Nonthaburi, Thailand during 2008-2009. Eight hundred thirteen patients were included in the study. The mean age of subjects +/- SD was 41 +/- 14 years and mean body weight +/- SD was 53 +/- 11 kilograms. The three leading co-morbid conditions were HIV infection (40%), diabetes (6%) and chronic liver disease (2%). Two-thirds of subjects had isolated pulmonary TB. Isoniazid, rifampicin and multi-drug resistance were seen in 13, 7 and 5%, respectively. After 1 year, 52% were cured or completed treatment, 19% transferred out, 12% defaulted, 9% were still on-going TB treatment, 7% had died and 1% had failed treatment. Survival rates at 2, 6 and 12 months were 93, 85 and 81% among HIV seropositive subjects; 96, 94 and 92% among HIV seronegative subjects and 98, 97 and 97% among subjects with unknown HIV status (p < 0.001). On multivariate analysis, death was associated with: TB/HIV co-infection (HR 2.8; 95% CI 1.6-5.0), low body weight (HR 1.6; 95% CI 1.2-2.3), being elderly (HR 1.4; 95% CI 1.1-1.8) and having extrapulmonary/disseminated TB (HR 2.2; 95% CI 1.1-4.2). HIV infection and diabetes were the most common co-morbidities among TB subjects in our study. The percent of patients with unfavorable outcomes was relatively high, particularly among HIV co-infected and elderly subjects. Further effort needs to be made to improve these unfavorable TB outcomes in Nonthaburi and Bangkok, Thailand.
Lo, Yi-Chun; Chen, Wan-Chin; Wang, Kwei-Feng; Chan, Pei-Chun
Recurrence after successful treatment for multidrug-resistant tuberculosis (MDR-TB) is challenging because of limited retreatment options. This study aimed to determine rates and predictors of MDR-TB recurrence after successful treatment in Taiwan. Recurrence rates were analyzed by time from treatment completion in 295 M DR-TB patients in a national cohort. Factors associated with MDR-TB recurrence were examined using a multivariate Cox regression analysis. Ten (3%) patients experienced MDR-TB recurrence during a median follow-up of 4.8 years. The overall recurrence rate was 0.6 cases per 1000 person-months. Cavitation on chest radiography was an independent predictor of recurrence (adjusted hazard ratio [aHR] = 6.3; 95% CI, 1.2–34). When the analysis was restricted to 215 patients (73%) tested for second-line drug susceptibility, cavitation (aHR = 10.2; 95% CI, 1.2–89) and resistance patterns of extensively drug-resistant TB (XDR-TB) or pre-XDR-TB (aHR = 7.3; 95% CI, 1.2–44) were associated with increased risk of MDR-TB recurrence. In Taiwan, MDR-TB patients with cavitary lesions and resistance patterns of XDR-TB or pre-XDR-TB are at the highest risk of recurrence. These have important implications for MDR-TB programs aiming to optimize post-treatment follow-up and early detection of recurrent MDR-TB. PMID:28125692
HAN, YI; ZHAO, QIUYUE; YU, DAPING; LIU, ZHIDONG
Chest wall tuberculosis (TB) is an endemic disease with a large number of variants. The condition affects numerous parts of the body and can penetrate the skin to form chronic open ulcers. Current treatment methods include oral anti-TB drugs and surgery. However, conventional drug treatments are not effective due to the difficulty in achieving an effective local concentration, and certain patients are unable to tolerate surgery. The recurrence rate for chest wall TB is high following surgery, and may result in the prolonged healing of wounds in certain patients, as well as chronic sinusitis and fistula formation. To identify a safe, simple, less invasive and more clinically effective treatment method, the present study investigated transdermal ultrasound-mediated anti-TB drug delivery. A total of 186 patients were selected and randomly divided into transdermal ultrasound, surgery and oral anti-TB drug only groups. Rifampicin was the drug delivered by transdermal ultrasound. The cure and efficiency rates were shown to be 87.10 and 93.55%, respectively, in the ultrasound treatment group. No statistically significant difference was observed in the cure rates between the transdermal ultrasound and surgery groups; however, a statistically significant difference was identified in the cure rates between the transdermal ultrasound and oral anti-TB drug only groups. Therefore, transdermal ultrasound technology was shown to deliver anti-TB drugs quickly and directly, which resulted in a high local concentration of the drug, overcoming the problem of obtaining an effective local drug concentration. The observations demonstrated that transdermal ultrasound-mediated drug delivery is an effective method by which to control TB, particularly when compared with traditional oral anti-TB therapy and surgery. PMID:25780447
Millet, Juan-Pablo; Orcau, Angels; Rius, Cristina; Casals, Marti; de Olalla, Patricia Garcia; Moreno, Antonio; Nelson, Jeanne L.; Caylà, Joan A.
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
Volchegorskiĭ, I A; Novoselov, P N; Astakhova, T V
The aim of this prospective placebo-controlled randomized study was to assess the effectiveness of ascorbic acid or emoxipin in the regimen of the therapy of infiltrative pulmonary tuberculosis. Emoxipin vs. ascorbic acid favored the eradication of tuberculosis mycobacteria. Both preparations decreased the blood level of the contra-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), shortened time to the closure of degeneration cavities in tubercular infiltrations, decreased the risk of the development of destructive forms, and lowered the need for surgical interventions for infiltrative pulmonary tuberculosis.
Kessel', M M; Perel'man, M I
A hundred and seven children and adolescents with intrathoracic lymph node (LTLN) tuberculosis were operated on. Late diagnosis and long-term ineffective antituberculous therapy lead to the development of complicated forms of ITLN tuberculosis in 44% of children. Computed tomography significantly determines extent, localization, the state of the adjacent tissue, and the phase of a tuberculous process, evaluates the efficiency of antituberculosis therapy, and ascertains the optimum time of a surgical intervention. Surgical removal of the involved ITLN is a highly effective operation causing the minimum number of complications. Bilateral successive one-stage removal of the involved lymph nodes is possible in children with bilateral ITLN tuberculosis.
Babalık, Aylin; Kılıçaslan, Zeki; Kızıltaş, Şule; Gencer, Serap; Öngen, Gül
Background: Tuberculosis is a public health problem and its transmission is a threat to the community. Aims: The aim of this study was to determine the factors influencing the treatment outcomes and the effectiveness of the National Tuberculosis Program (NTP) in relation to the application of the directly observed treatment, short-course (DOTS) program in various sites in Istanbul, Turkey. Study Design: Case-Control Study Methods: A case-control study was used, where cases and controls were randomly selected from the Turkish Tuberculosis National Database, which includes complete data on treatment outcomes for patients recorded in the database from January 1, 2006 to December 31, 2009 and had one year follow-up. Results: The case group was composed of 464 patients with adverse outcome, while the control group was composed of 441 patients who had been cured of disease. Factors associated with adverse treatment outcome were >65 years of age (OR: 3.39 (1.99–5.76)) ; male gender (OR:2.11 (1.49–2.99)); born outside Turkey (OR: 5.48 (2.13–14.04)); co-morbidity (OR: 1.85 (1.29–2.65)); bilateral radiologic lesions (OR: 2.07 (1.41–3.00); previous treatment history (OR: 3.99 (2.78–5.74)); 3rd month positive microscopy (OR: 4.96 (3.04–8.09)) and any H&R +/− others multidrug resistant (MDR) resistance (OR: 22.64 (6.92–74.08)). There was no association between the adverse treatment outcome and the application site of direct observation treatment, short course (DOTS) delivery and the supervisors. Conclusion: Our findings indicate similar quality in DOTS application and supervision among patients with or without adverse treatment outcomes. However, patients with certain characteristics should be carefully monitored and aggressively treated. PMID:25207101
Sirinak, Chawin; Kittikraisak, Wanitchaya; Pinjeesekikul, Duangporn; Charusuntonsri, Pricha; Luanloed, Phinai; Srisuwanvilai, La-ong; Nateniyom, Sriprapa; Akksilp, Somsak; Likanonsakul, Sirirat; Sattayawuthipong, Wanchai; Burapat, Channawong; Varma, Jay K
Background The occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients. Methods Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BR), complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines. Results Of 769 enrolled patients, 752 (98%) had serologic testing performed for viral hepatitis: 70 (9%) were reactive for HBsAg, 237 (31%) for anti-HCV, and 472 (63%) non-reactive for both markers. At the beginning of TB treatment, 18 (26%) patients with HBsAg reactivity had elevated liver function tests compared with 69 (15%) patients non-reactive to any viral marker (p = 0.02). At the end of TB treatment, 493 (64%) were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1–4.3) and having low TB knowledge (AOR, 1.8; CI, 1.0–3.0). Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0–23.2) and living in Bangkok (AOR, 15.8; CI, 9.4–26.5). The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker. Conclusion Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus infection, were
Theron, Grant; Peter, Jonny; Richardson, Marty; Warren, Rob; Dheda, Keertan; Steingart, Karen R
Background Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. Objectives To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. Search methods We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. Selection criteria We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Data collection and analysis Two review authors independently extracted data and assessed
Parumasivam, T; Chan, J G Y; Pang, A; Quan, D H; Triccas, J A; Britton, W J; Chan, H K
Thioridazine is an orally administered antipsychotic drug with potential for treatment of drug-resistant tuberculosis (TB). However, drug-induced adverse cardiac effects have been reported when thioridazine was used at an efficacious oral dose of 200mg/day to treat TB. Pulmonary delivery of thioridazine could be a rational approach to reduce dose-related side effects while enabling high drug concentrations at the primary site of infection. The present study compares in vitro aerosol performance, storage stability, and in vitro antimicrobial activity and cytotoxicity of two inhalable powders composed of thioridazine and a first-line anti-TB drug, rifapentine. Formulation 1 is a combination of amorphous thioridazine and crystalline rifapentine, while Formulation 2 consisted of both drugs as amorphous forms. Both thioridazine-rifapentine formulations were found suitable for inhalation with a total fine particle fraction (<5μm) of 68-76%. The two powders had similar MIC90 to rifapentine alone, being 0.000625μg/mL and 0.005μg/ml against Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv, respectively. In contrast, thioridazine alone had a MIC90 of 12.5μg/mL and 500μg/mL, against M. tuberculosis H37Ra and M. tuberculosis H37Rv, respectively, demonstrating no synergistic anti-TB activity. However, thioridazine and rifapentine in a ratio of 1:3 enhanced the killing of M. tuberculosis H37Ra within the human monocyte-derived macrophages (THP-1) compared to the single drug treatments. Both powders showed an acceptable half maximal inhibitory concentration (IC50) of 31.25μg/mL on both THP-1 and human lung epithelial (A549) cells. However, Formulation 1 showed greater chemical stability than Formulation 2 after three months of storage under low humidity (vacuum) at 20±3°C. In conclusion, we have demonstrated a novel inhalable powder consisted of amorphous thioridazine and crystalline rifapentine (Formulation 1) with a good aerosol performance, potent anti
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
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.
Oray, Merih; Zakiev, Zaur; Çağatay, Tülin; Tuğal-Tutkun, İlknur
Objectives: To compare the results of systemic antitubercular therapy (ATT) and immunomodulatory therapy (IMT) in patients with serpiginous choroiditis (SC) or multifocal serpiginoid choroiditis (MSC). Materials and Methods: The clinical records of 28 patients with SC and MSC were reviewed. Patients were divided into 2 groups according to the treatment applied. Group 1 included 12 patients with MSC and 5 with SC treated with ATT and corticosteroid (CS); group 2 included 9 patients with MSC and 2 with SC treated with conventional IMT, interferon alpha-2a, and/or CS monotherapy. Results: In group 1, clinical remission was achieved in 12/12 MSC and 3/5 SC (total 15/17) patients with administration of ATT for 1 year. Two patients (1 SC, 1 MSC) had reactivation 2 and 7 months after cessation of ATT. Two patients with recurrence after completion of ATT and 2 patients resistant to ATT received IMT ± CS therapy. In group 2, clinical remission was achieved in 7/9 MSC and 2/2 SC (total 9/11) patients after 1 year of treatment. Recurrent inflammation was observed in 2 MSC patients 2 and 112 months after initiation of therapy, but responded well to local/systemic CS or IMT modification, and clinical remission was achieved in 7.8±4.3 months. Cumulative dose of CS was higher in group 2 (p=0.057). Nine of 12 MSC patients treated with ATT and 4/9 MSC patients treated with IMT achieved remission (p=0.203). One of 5 SC patients treated with ATT and 2/2 SC patients treated with IMT achieved remission (p=0.142). Conclusion: Although a statistically significant result could not be achieved in this small case series, our results suggest that ATT may be an appropriate first choice in the treatment of MSC associated with latent tuberculosis, and may be administered in patients with SC who are unresponsive to IMT.
Adhvaryu, Meghna R; Reddy, Narsimha M; Vakharia, Bhasker C
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
Brigden, Grania; Hewison, Cathy; Varaine, Francis
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.
Diel, Roland; Loddenkemper, Robert; Zellweger, Jean-Pierre; Sotgiu, Giovanni; D'Ambrosio, Lia; Centis, Rosella; van der Werf, Marieke J; Dara, Masoud; Detjen, Anne; Gondrie, Peter; Reichman, Lee; Blasi, Francesco; Migliori, Giovanni Battista
The introduction of new rapid diagnostic tools for tuberculosis (TB) and the promising TB drugs pipeline together with the development of a new World Health Organization Strategy post 2015 allows new discussions on how to direct TB control. The European Respiratory Society's European Forum for TB Innovation was created to stimulate discussion on how to best take advantage of old and new opportunities, and advances, to improve TB control and eventually progress towards the elimination of TB. While TB control is aimed at reducing the incidence of TB by early diagnosis and treatment of infectious cases of TB, TB elimination requires focus on sterilising the pool of latently infected individuals, from which future TB cases would be generated. This manuscript describes the three core components that are necessary to implement the elimination strategy fully. 1) Improve diagnosis of latent TB infected individuals. 2) Improve regimens to treat latent TB infection. 3) ensure public health commitment to make both 1) and 2) possible. Old and new evidence is critically described, focusing on the European commitment to reach elimination and on the innovative experiences and best practices available.
Teunissen, M W; Bakker, W; Meerburg-Van der Torren, J E; Breimer, D D
The influence of an 8-day therapy with rifampicin (600 mg daily) was studied on antipyrine plasma clearance and metabolite formation in seven patients with tuberculosis (age 18-79 years), who were also treated with isoniazid and pyrazinamide. After rifampicin treatment the elimination half-life of antipyrine had decreased in all patients from 12.9 +/- 5.0 to 8.8 +/- 2.0 h (P less than 0.05). Antipyrine clearance had increased from 2.2 +/- 0.9 to 2.9 +/- 0.7 l/h (P less than 0.05), while no change in apparent volume of distribution was observed. The increase in antipyrine clearance was primarily due to a selective increase in the rate of formation of norantipyrine by 80% from 6.9 +/- 3.4 to 12.4 +/- 3.4 ml/min. Rifampicin seems to induce preferentially the cytochrome P-450 (iso-) enzyme(s) involved in the demethylation of antipyrine to norantipyrine. Other pathways of antipyrine metabolism were hardly affected. This provides further evidence for the involvement of different iso-enzymes of the cytochrome P-450 system in antipyrine metabolism in man. PMID:6508979
Sassaki, Cinthia Midori; Scatena, Lucia Marina; Gonzales, Roxana Isabel Cardozo; Ruffino-Netto, Antonio; Hinos, Paula; Villa, Tereza Cristina Scatena
Based on data available in the Information System for Notifiable Diseases, predictive factors of favorable results were identified in the treatment of pulmonary tuberculosis, diagnosed between 2001 and 2004 and living in Recife-PE, Brazil. Uni- and multivariate logistic regression methods were used. In multivariate analysis, the following factors remained: Age (years), 0 to 9 (OR = 4.27; p = 0.001) and 10 to 19 (OR = 1.78; p = 0.011), greater chance of cure than over 60; Education (years), 8 to 11 (OR = 1.52; p = 0.049), greater chance of cure than no education; Type of entry, ne wcase s (OR = 3.31; p < 0.001) and relapse (OR = 3.32; p < 0.001), greater chances of cure than restart after abandonment; Time (months) 2, 5--6 (OR = 9.15; p < 0.001); 6--9 (OR = 27.28; p < 0.001) and More than 9 (OR = 24.78; p < 0.001), greater chances of cure than less than 5; Health Unit District, DSII (OR = 1.60; p = 0.018) and DSIIV (OR = 2.87; p < 0.001), greater chance sof cure than DS II.
Verguet, Stéphane; Laxminarayan, Ramanan; Jamison, Dean T
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.
Blanc, Francois-Xavier; Havlir, Diane V; Onyebujoh, Philip C; Thim, Sok; Goldfeld, Anne E; Delfraissy, Jean-Francois
Currently, there are limited data to guide the management of highly active antiretroviral therapy (HAART) for human immunodeficiency virus type 1 (HIV-1)-infected patients with active tuberculosis (TB), the leading cause of death among individuals with acquired immunodeficiency syndrome (AIDS) in resource-limited areas. Four trials to take place in Southeast Asian, African, and South American countries will address the unresolved question of the optimal timing for initiation of HAART in patients with AIDS and TB: (1) Cambodian Early versus Late Introduction of Antiretrovirals (CAMELIA [ANRS 1295/NIH-CIPRA KH001]), (2) Adult AIDS Clinical Trials Group A5221, (3) START, and (4) a trial sponsored by the World Health Organization/Special Programme for Research and Training in Tropical Diseases. Two other clinical questions regarding patients with TB and HIV-1 coinfection are also undergoing evaluation: (1) the benefits of short-term HAART when CD4 cell counts are >350 cells/mm(3) (PART [NIH 1 R01 AI051219-01A2]) and (2) the efficacy of a once-daily HAART regimen in treatment-naive patients (BKVIR [ANRS 129]). Here, we present an overview of these ongoing or planned clinical studies, which are supported by international agencies.
Carrol, E D; Clark, J E; Cant, A J
Tuberculosis (TB) is a serious disease of global importance, with a rising incidence in the developed world in recent years. Tuberculous lymphadenitis, tuberculous meningitis, osteoarticular tuberculosis and miliary tuberculosis are some of the more well-recognised manifestations of non-pulmonary TB in childhood. The diagnosis of non-pulmonary TB poses a particular challenge for clinicians because of the protean ways in which the disease presents. The omission of tuberculosis from the differential diagnosis of patients with obscure illnesses and the relatively insensitive bacteriological methods for detecting Mycobacterium tuberculosis add to the complexity of the problem. A high index of suspicion is required in order to avoid delays in diagnosis which may influence treatment outcome. The advent of DNA amplification techniques such as the polymerase chain reaction may herald a promising new era in the prompt and accurate management of extrapulmonary tuberculosis.
Wu, Jiun-Ting; Chiu, Chien-Tung; Wei, Yu-Feng; Lai, Yung-Fa
OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. PMID:26106962
Adenager, Getinet Shewaseged; Alemseged, Fessahaye; Asefa, Henok
Background. Early detection and diagnosis of tuberculosis (TB) and the timely commencement of antituberculosis (anti-TB) treatment are the parts of efficient tuberculosis prevention and control program. Delay in the commencement of anti-TB treatment worsens the prognosis and increases the risk of death and the chance of transmission in the community and among health care workers. Objective. To assess tuberculosis treatment delay and associated factors among pulmonary TB patients in Addis Ababa, Ethiopia. Methods. A cross-sectional study was conducted in 10 public and 10 private health facilities that provide TB treatment. The data were collected from 425 newly registered pulmonary TB patients using pretested structured questionnaire from April to June 2012. Data were entered in EPI info version 3.5.1 and analyzed using SPSS version 16.0. Findings. The median durations of a patient, health care system, and total treatment delays were 17, 9, and 35 days, respectively. Overall 179 (42.1%), 233 (54.8%), and 262 (61.6%) of patients experienced patient delay, health care system delay, and total treatment delay, respectively. Distance more than 2.5 km from TB treatment health facility [AOR = 1.6, 95% CI (1.1–2.5)] and the presence of TB-associated stigma [AOR = 2.1, 95% CI (1.3, 3.4)] indicate higher odds of patient delay, whereas, being unemployed, patients with the hemoptysis symptom complain indicated lower odds of health care system delay [AOR = 0.41, 95% CI (0.24, 0.70)] and [AOR = 0.61 (0.39, 0.94)], respectively. Conclusions. A significant proportion of clients experienced patient and health care system delay. Thus, there is a need for designing and implementing appropriate strategies to decrease the delays. Efforts to reduce delays should give focus on integrating prevention programs such as active case detection and expanding access to TB care. PMID:28348887
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
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
Azman, Andrew S.; Cobelens, Frank G.; Dowdy, David W.
Background In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality. Methods We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology. Results Despite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4–52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6–55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20–74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025. Conclusions Expansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected
Chadha, V. K.; Laxminarayan, R.; Arinaminpathy, N.
SUMMARY BACKGROUND: There is an urgent need for improved estimations of the burden of tuberculosis (TB). OBJECTIVE: To develop a new quantitative method based on mathematical modelling, and to demonstrate its application to TB in India. DESIGN: We developed a simple model of TB transmission dynamics to estimate the annual incidence of TB disease from the annual risk of tuberculous infection and prevalence of smear-positive TB. We first compared model estimates for annual infections per smear-positive TB case using previous empirical estimates from China, Korea and the Philippines. We then applied the model to estimate TB incidence in India, stratified by urban and rural settings. RESULTS: Study model estimates show agreement with previous empirical estimates. Applied to India, the model suggests an annual incidence of smear-positive TB of 89.8 per 100 000 population (95%CI 56.8–156.3). Results show differences in urban and rural TB: while an urban TB case infects more individuals per year, a rural TB case remains infectious for appreciably longer, suggesting the need for interventions tailored to these different settings. CONCLUSIONS: Simple models of TB transmission, in conjunction with necessary data, can offer approaches to burden estimation that complement those currently being used. PMID:28284250
Eing, Bodo R.; Becker, Andrea; Sohns, Arthur; Ringelmann, Ronald
The new Roche Cobas Amplicor Mycobacterium tuberculosis assay, which is a semiautomated version of the manually performed Roche Amplicor M. tuberculosis test, was compared to culture and an IS6110-based in-house PCR protocol. A total of 1,681 specimens from 833 patients, including specimen types other than sputum, were tested in parallel by both the in-house PCR and the Cobas Amplicor M. tuberculosis assay. After we resolved discrepant PCR results, the sensitivity, specificity, and positive and negative predictive values for the Cobas Amplicor M. tuberculosis assay were 66.33, 99.71, 94.36, and 97.66%, respectively. The corresponding values for the in-house PCR were 91.08, 99.85, 97.87, and 99.37%, respectively. For culture- and smear-positive specimens, the sensitivity of the Cobas Amplicor M. tuberculosis test was 96.42% (in-house PCR, 100%). If only smear-negative sputum specimens were considered, the Cobas Amplicor M. tuberculosis assay exhibited a sensitivity of 45.45% (in-house PCR, 63.63%) relative to that of culture. With a modified protocol for DNA extraction (washing of samples plus ultrasonication), both PCR methods performed better with gastric aspirates than with sputum samples (sensitivity of the Cobas Amplicor M. tuberculosis assay with smear-negative gastric aspirates, 70.00%; sensitivity of in-house PCR, 90.00%). With dithiothreitol being used for liquefaction of specimens in this study, the Cobas Amplicor M. tuberculosis assay exhibited an inhibition rate of 9.16%. In our view, the new Cobas Amplicor M. tuberculosis test (i) is well suited for typing of smear-positive specimens, (ii) may also be applied to gastric aspirates and other types of specimens if DNA extraction methods are modified appropriately, and (iii) exhibits a sensitivity with smear-negative sputum specimens which makes it recommendable that a minimum of three samples from the same patient be tested. PMID:9650955
[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].
Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena
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.
Cheng, Zhaohui; Wang, Jian; Zheng, Qixin; Wu, Yongchao; Guo, Xiaodong
Abstract 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
Ali, Ahmed Osman Ahmed; Prins, Martinus Hendrik
Introduction Despite the Treatment pulmonary TB patients, defaulting from treatment may remain the major challenge to control TB. In addition, it increases the risk of drug resistance, relapse, and death and may prolong infectiousness. Our objective was to identify determinants of treatment defaulting among TB patients in Khartoum State, Sudan. Methods We conducted a case-control study where the patients defaulting from treatment were considered as ‘cases’ and those completing treatment as ‘controls’. Between May 2010 to May 2011. Results There were 2727 TB patients who attended TB treatment clinics during study period. Out of these 2399 patients (86%) had continued their treatment while 328 patients (14%) had interrupted it. 105 cases were traced and interviewed. In addition 210 patients who had continued their treatment were included (controls). In the multivariate analysis the variables that remained in the model were: residential locality (rural area) (OR 2.58; 95% CI 1.4 -4.67), patients moving or changing address (OR 5.47; 95% CI 2,90- 10-35), absence of family support (OR 2.14; 95% CI 1.12 - 4.11), and occupation (blue collar work) (OR 2.38; 95% CI 1.39 -4.10). Conclusion The results of this study conclude some socio-demographic factors influence defaulting of TB treatment. We believe that the findings are applicable to current situation of TB management and control in Sudan and other developing countries PMID:28292043
Lidder, Surjit; Lang, Kathryn; Haroon, Mallick; Shahidi, Mitra; El-Guindi, Magdi
Extrapulmonary manifestations of tuberculosis are reported in less than one in five cases with the knee affected in 8% after the spine and hip. We report a case of isolated highly erosive tuberculosis of the knee presenting in a previously fit Vietnamese woman. The difficulties of diagnosis, modalities of chemotherapeutic management, and surgical treatment are discussed. PMID:21808686
Fatima, Razia; Qadeer, Ejaz; Yaqoob, Aashifa; Haq, Mahboob ul; Majumdar, Suman S.; Shewade, Hemant D.; Stevens, Robert; Creswell, Jacob; Mahmood, Nasir; Kumar, Ajay M. V.
Background Currently, only 62% of incident tuberculosis (TB) cases are reported to the national programme in Pakistan. Several innovative interventions are being recommended to detect the remaining ‘missed’ TB cases. One such intervention involved expanding contact investigation to the community using the Xpert MTB/RIF test. Methods This was a before and after intervention study involving retrospective record review. Passive case finding and household contact investigation was routinely done in the pre-intervention period July 2011-June 2013. Four districts with a high concentration of slums were selected as intervention areas; Lahore, Rawalpindi, Faisalabad and Islamabad. Here, in the intervention period, July 2013-June 2015, contact investigation beyond household was conducted: all people staying within a radius of 50 metres (using Geographical Information System) from the household of smear positive TB patients were screened for tuberculosis. Those with presumptive TB were investigated using smear microscopy and the Xpert MTB/RIF test was performed on smear negative patients. All the diagnosed TB patients were linked to TB treatment and care. Results A total of 783043 contacts were screened for tuberculosis: 23741(3.0%) presumptive TB patients were identified of whom, 4710 (19.8%) all forms and 4084(17.2%) bacteriologically confirmed TB patients were detected. The contribution of Xpert MTB/RIF to bacteriologically confirmed TB patients was 7.6%. The yield among investigated presumptive child TB patients was 5.1%. The overall yield of all forms TB patients among investigated was 22.3% among household and 19.1% in close community. The intervention contributed an increase of case detection of bacteriologically confirmed tuberculosis by 6.8% and all forms TB patients by 7.9%. Conclusion Community contact investigation beyond household not only detected additional TB patients but also increased TB case detection. However, further long term assessments and cost
Borgdorff, M W; Veen, J; Kalisvaart, N A; Broekmans, J F; Nagelkerke, N J
The aim of this study was to assess the rate of defaulting from treatment among tuberculosis patients diagnosed in the Netherlands in the period 1993-1997, whether risk groups for defaulting can be identified at the start of treatment and the trend of defaulting over time. The Netherlands Tuberculosis Register provided data on all patients diagnosed in the Netherlands during the period 1993-1997. Defaulting probabilities were determined using Kaplan-Meier survival analysis and risk factors were identified with Cox's proportional hazard analysis. Of 7,529 patients with reported treatment outcome, 718 (10%) defaulted or left the country within 1 yr after starting treatment. Defaulting probabilities were 9% (95% confidence interval (CI) 8-10%) among 5,256 patients in low-risk groups, 17% (95% CI 14-19%) among 1,437 asylum seekers and 29% (95% CI 24-34%) among 836 patients in other high-risk groups (other recent immigrants, illegal immigrants, the homeless, prisoners and nationals from Eastern Europe). Defaulting probabilities decreased over time from 12% in 1993 to 7% in 1997. Risk groups for defaulting can be recognized at the start of treatment. The decreasing defaulting probabilities were probably due in part to shortening treatment from 9 to 6 months and improved follow-up of asylum seekers. However, additional measures are needed to reduce defaulting among the homeless, recent immigrants, illegal immigrants and prisoners.
Juarez-Reyes, Maria; Gallivan, Mark; Chyorny, Alexander; O'Keeffe, Linda; Shah, Neha S
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.
Juarez-Reyes, Maria; Gallivan, Mark; Chyorny, Alexander; O'Keeffe, Linda; Shah, Neha S.
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
Kirenga, Bruce J.; Levin, Jonathan; Ayakaka, Irene; Worodria, William; Reilly, Nancy; Mumbowa, Francis; Nabanjja, Helen; Nyakoojo, Grace; Fennelly, Kevin; Nakubulwa, Susan; Joloba, Moses; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Mugerwa, Roy D.; Smith, Peter G.; Ellner, Jerrold J.; Jones-López, Edward C.
Background In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda Methods and findings Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 – 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 – 4.01, P = 0.045). Conclusion Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART. PMID:24608875
Feruglio, S L; Tonby, K; Kvale, D; Dyrhol-Riise, A M
Biomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4(+) T regulatory cells (Tregs ) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN-γ and single IFN-γ-producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2(+) cells increased over time for both CD4(+) and CD8(+) T cells. The Treg subsets CD25(high) CD127(low) , CD25(high) CD147(++) and CD25(high) CD127(low) CD161(+) expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25(high) CD127(low) CD39(+) Tregs remained unchanged. The fraction of CD25(high) CD127(low) Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4(+) and CD8(+) T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further.
Mejuto, Beatriz; Tuñez, Victoria; del Molino, María Luisa Pérez; García, Rosario
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
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
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
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
Desjardin, L. e.; Chen, Y.; Perkins, M. D.; Teixeira, L.; Cave, M. D.; Eisenach, K. D.
Mycobacterium tuberculosis can persist in sputum for long periods of time after the initiation of antituberculosis chemotherapy. The purpose of this study was to determine whether quantitative estimates of M. tuberculosis DNA in sputum correlate with the numbers of viable bacilli and thus measure the therapeutic response of patients during treatment. Two methods of M. tuberculosis DNA quantification were examined by using DNA isolated from sputum specimens serially collected during the course of chemotherapy. A competitive PCR assay was compared to an automated system of real-time quantification with the ABI Prism 7700 Sequence Detection System (TaqMan). The ABI 7700 system uses standard PCR in conjunction with a fluorogenic probe in which the intensity of fluorescence is proportional to the amount of target DNA present. The results showed that both PCR systems are reproducible and accurate. The amounts of M. tuberculosis DNA quantified in sputum corresponded well with the numbers of acid-fast bacilli (AFB) counted by microscopy. Before initiation of antituberculosis therapy, measures of AFB, M. tuberculosis DNA, and cultivable bacilli were similar, suggesting that quantification of DNA is a good method for measuring the initial bacillary load. However, the rate of disappearance of both AFB and M. tuberculosis DNA did not correlate with the decline in cultivable bacilli in the specimen; therefore, these tests are not appropriate for monitoring treatment efficacy. PMID:9650945
Pathak, Vikas; Shepherd, Ray W.
Tracheobronchial tuberculosis (TBTB) is reported in approximately 10% to 39% of the patients with pulmonary tuberculosis. It is defined as the tubercle infection of the trachea and or bronchi. Due to its non-specific presentation, insidious onset and normal chest radiography in about 10–20% of the patients, the diagnosis is delayed. Bronchoscopy is the most definite method of diagnosis which provides adequate specimens for microbiological and histopathological diagnosis. Tracheobronchial stenosis is one of the most common long term complications of TBTB resulting in significant morbidity. It is estimated that 90% of patients with TBTB have some degree of tracheal and or bronchial stenosis. In this review article, we will discuss the pathogenesis, symptoms, imaging, bronchoscopic findings, and treatment of TBTB and management of tracheobronchial stenosis. PMID:28149582
Background Since 2003, the Global Fund has supported the scale-up of HIV/AIDS, tuberculosis and malaria control in low- and middle-income countries. This paper presents and discusses a methodology for estimating the lives saved through selected service deliveries reported to the Global Fund. Methods Global Fund-supported programs reported, by end-2007, 1.4 million HIV-infected persons on antiretroviral treatment (ARV), 3.3 million new smear-positive tuberculosis cases detected in DOTS (directly observed TB treatment, short course) programs, and 46 million insecticide-treated mosquito nets (ITNs) delivered. We estimated the corresponding lives saved using adaptations of existing epidemiological estimation models. Results By end-2007, an estimated 681,000 lives (95% uncertainty range 619,000-774,000) were saved and 1,097,000 (993,000-1,249,000) life-years gained by ARV. DOTS treatment would have saved 1.63 million lives (1.09 - 2.17 million) when compared against no treatment, or 408,000 lives (265,000-551,000) when compared against non-DOTS treatment. ITN distributions in countries with stable endemic falciparum malaria were estimated to have achieved protection from malaria for 26 million of child-years at risk cumulatively, resulting in 130,000 (27,000-232,000) under-5 deaths prevented. Conclusions These results illustrate the scale of mortality effects that supported programs may have achieved in recent years, despite margins of uncertainty and covering only selected intervention components. Evidence-based evaluation of disease impact of the programs supported by the Global Fund with international and in-country partners must be strengthened using population-level data on intervention coverage and demographic outcomes, information on quality of services, and trends in disease burdens recorded in national health information systems. PMID:20433714
Chowdhury, Md Rocky Khan; Rahman, Md Shafiur; Mondal, Md Nazrul Islam; Sayem, Abu; Billah, Baki
Stigma, considered a social disease, is more apparent in developing societies which are driven by various social affairs, and influences adherence to treatment. The aim of the present study was to examine levels of social stigma related to tuberculosis (TB) in sociodemographic context and identify the effects of sociodemographic factors on stigma. The study sample consisted of 372 TB patients. Data were collected using stratified sampling with simple random sampling techniques. T tests, chi-square tests, and binary logistic regression analysis were performed to examine correlations between stigma and sociodemographic variables. Approximately 85.9% of patients had experienced stigma. The most frequent indicator of the stigma experienced by patients involved problems taking part in social programs (79.5%). Mean levels of stigma were significantly higher in women (55.5%), illiterate individuals (60.8%), and villagers (60.8%) relative to those of other groups. Chi-square tests revealed that education, monthly family income, and type of patient (pulmonary and extrapulmonary) were significantly associated with stigma. Binary logistic regression analysis demonstrated that stigma was influenced by sex, education, and type of patient. Stigma is one of the most important barriers to treatment adherence. Therefore, in interventions that aim to reduce stigma, strong collaboration between various institutions is essential.
Sahebi, Leyla; Ansarin, Khalil; Mohajeri, Parviz; Khalili, Majid; Monfaredan, Amir; Farajnia, Safar; Zadeh, Simin Khayyat
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
Rusen, I D; Enarson, Donald A
Tuberculosis was declared a global public health emergency in 1993. In 2003, only 45% of the world's estimated new smear-positive tuberculosis cases were detected-well below the 70% global case detection target set by the World Health Organization. The FIDELIS (Fund for Innovative DOTS Expansion Through Local Initiatives to Stop TB) initiative is a new global disease control initiative that has been developed to rapidly assess and implement innovative approaches to increase tuberculosis case detection. To date, 32 projects have been approved-covering approximately 378 million people in 13 countries-24 (75%) of which are in the world's 6 highest-burden countries. A wide range of target populations and interventions have been incorporated into successful FIDELIS projects. The FIDELIS initiative may serve as a model to discover best practices to address other urgent global public health problems.
Rusen, I. D.; Enarson, Donald A.
Tuberculosis was declared a global public health emergency in 1993. In 2003, only 45% of the world’s estimated new smear-positive tuberculosis cases were detected—well below the 70% global case detection target set by the World Health Organization. The FIDELIS (Fund for Innovative DOTS Expansion Through Local Initiatives to Stop TB) initiative is a new global disease control initiative that has been developed to rapidly assess and implement innovative approaches to increase tuberculosis case detection. To date, 32 projects have been approved—covering approximately 378 million people in 13 countries—24 (75%) of which are in the world’s 6 highest-burden countries. A wide range of target populations and interventions have been incorporated into successful FIDELIS projects. The FIDELIS initiative may serve as a model to discover best practices to address other urgent global public health problems. PMID:16317206
Chapman, Kimberley N.; Pevzner, Eric; Mangan, Joan M.; Breese, Peter; Lamunu, Dorcas; Shrestha-Kuwahara, Robin; Nakibali, Joseph G.; Goldberg, Stefan V.
Background Ethical principles obligate researchers to maximize study participants’ comprehension during the informed consent process for clinical trials. A pilot evaluation of the consent process was conducted during an international clinical trial of treatment for pulmonary tuberculosis to assess the feasibility of conducting an evaluation in a larger population and to guide these future efforts. Methods Study staff administered an informed consent assessment tool (ICAT) to a convenience sample of trial participants, measuring comprehension of consent components as derived from the Common Rule and FDA Title 21 Part 50, and satisfaction with the process. Participating site staff completed a consent process questionnaire about consent practices at their respective sites and provided improvement recommendations. ICAT scores and corresponding practices were compared where both were completed. Results ICATs (n = 54) were submitted from one site in Spain (n = 10), one in Uganda (n = 30), and five in the United States (n = 14). Participants were primarily male (76%), born in Africa (n = 31, 57%), and had a median age of 27 years (interquartile range [IQR]: 24–42). Median ICAT scores were 80% (IQR: 67–93) for comprehension and 89% (IQR: 78–100) for satisfaction. Ugandan participants scored higher than participants from other sites on comprehension (87% vs. 64%) and satisfaction (100% vs. 78%). Staff from 14 sites completed consent process questionnaires. Median ICAT scores for comprehension and satisfaction were higher at sites that utilized visual aids. Practice recommendations included shorter forms, simpler documents, and supplementary materials. Conclusions Participants achieved high levels (≥80%) of comprehension and satisfaction with their current consent processes. Higher ICAT scores at one site suggest an additional evaluation may identify approaches to improve comprehension and satisfaction in future trials. Through this pilot evaluation, complexities
Millet, Juan-Pablo; Shaw, Evelyn; Orcau, Àngels; Casals, Martí; Miró, Jose M.; Caylà, Joan A.
Background Tuberculosis (TB) recurrence can be due to reinfection or relapse. The contribution of each to TB incidence and the factors associated with recurrence are not well known. Effectiveness of TB control programs is assessed in part by recurrence rates. The aim of this study was to establish the recurrence rate of TB in Barcelona, the associated risk factors and the role of reinfection. Methods A population-based retrospective longitudinal study was performed in Barcelona, Spain. TB patients with positive culture results who completed treatment between Jan 1st, 2003 and Dec 31st, 2006 were followed-up until December 31st, 2009 by the TB Control Program. The incidence rate of recurrence was calculated per person-year of follow-up (py). Kaplan-Meier and Cox regression methods were used for the survival analysis by calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results Of the 1,823 TB cases identified, 971 fulfilled the inclusion criteria and 13 (1.3%) had recurrent TB. The recurrence rate was 341 cases per 100,000 py, 13 times higher than the TB incidence of the general population. Likelihood of TB recurrence at the 1st, 3rd and 5th year of follow-up was 0.1%, 1.4% and 1.6%, respectively. Factors associated with recurrence were HIV infection (HR: 4.7, CI: 1.4–15.7), living in the inner city district (HR: 3.9, CI: 1.3–11.8) and history of TB treatment (HR: 5.2, CI: 1.7–16.2). Genotyping results of recurrent cases were available for 6 patients (3 reinfections and 3 relapses). Conclusion The rate of TB recurrence in Barcelona is low and most episodes occur within the first three years. Patients at higher risk of recurrence are co-infected with HIV, living in neighborhoods with high TB incidence or with a history of TB treatment. When available, genotyping results help determine whether the recurrence is due to reinfection or relapse. PMID:23776440
Mendonça, Angela Marcia Cabral; Kritski, Afrânio Lineu; Land, Marcelo Gerardin Poirot; Sant’Anna, Clemax Couto
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
den Hertog, Alice L; de Vos, Alex F; Klatser, Paul R; Anthony, Richard M
Recently we proposed exploring the potential of treatment stimulated testing as diagnostic method for tuberculosis (TB). An infection controlled placebo controlled mouse study was performed to investigate whether serum cytokine levels changed measurably during the early phase of TB chemotherapy. Serum was collected prior to and during the first 3 weeks of isoniazid (INH) and rifampicin (RIF) chemotherapy, and levels of 23 selected cytokines/chemokines were measured using a liquid bead array. The serum levels of IFNγ, IP-10, MIG, MCP-1, IL-17 and IL-6 were elevated in the TB infected mice compared to non-infected mice at least at 1 time point measured. In infected mice, IFNγ, IP-10, MIG and MCP-1 levels decreased within 7 days of treatment with RIF+INH compared to placebo. Treatment of non-infected mice in the absence of tuberculosis infection had no effect on these cytokines. IL-17 and IL-6 had decreased to baseline in all infected mice prior to the initiation of treatment. This study demonstrates that systemic levels of some cytokines, more specifically IFNγ, IP-10, MIG and MCP-1, rapidly and specifically change upon starting TB chemotherapy only in the presence of infection in a mouse model. Thus, IFNγ, IP-10, MIG and MCP-1 are promising 'Treat-to-Test' targets for the diagnosis of TB and deserve further investigation in a study on human TB suspects.
van Rensburg, Ilana C.; Kleynhans, Léanie; Keyser, Alana; Walzl, Gerhard
Abstract Introduction Studies show that B‐cells, in addition to producing antibodies and antigen‐presentation, are able to produce cytokines as well. These include regulatory cytokines such as IL‐10 by regulatory B‐cells. Furthermore, a rare regulatory subset of B‐cells have the potential to express FasL, which is a death‐inducing ligand. This subset of B‐cells have a positive role during autoimmune disease, but has not yet been studied during tuberculosis. These FasL‐expressing B‐cells are induced by bacterial LPS and CpG, thus we hypothesized that this phenotype might be induced during tuberculosis as well. Methods B‐cells from participants with TB (at diagnosis and during treatment) and controls were collected, and analyzed by means of real‐time PCR and flow cytometry. In addition to this, BAL was collected from TB participants as well and analyzed by means of MAGPix (multi‐cytokine) technology. Results Gene expression analysis show that FASL transcript levels increase by the end of treatment. Similarly, phenotypic analysis show that there is a higher frequency of FasL‐expressing B‐cells by the end of treatment. Conclusion Collectively, these results indicate that these FasL‐expressing B‐cells are being induced during anti‐TB treatment, and thus may play a positive role. Further studies are required to elucidate this. PMID:28250925
Theron, Grant; Peter, Jonny; Dowdy, David; Langley, Ivor; Squire, S Bertel; Dheda, Keertan
In tuberculosis-endemic settings, patients are often treated empirically, meaning that they are placed on treatment based on clinical symptoms or tests that do not provide a microbiological diagnosis (eg, chest radiography). New tests for tuberculosis, such as the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA), are being implemented at substantial cost. To inform policy and rationally drive implementation, data are needed for how these tests affect morbidity, mortality, transmission, and population-level tuberculosis burden. If people diagnosed by use of new diagnostics would have received empirical treatment a few days later anyway, then the incremental benefit might be small. Will new diagnostics substantially improve outcomes and disease burden, or simply displace empirical treatment? Will the extent and accuracy of empirical treatment change with the introduction of a new test? In this Personal View, we review emerging data for how empirical treatment is frequently same-day, and might still be the predominant form of treatment in high-burden settings, even after Xpert implementation; and how Xpert might displace so-called true-positive, rather than false-positive, empirical treatment. We suggest types of studies needed to accurately assess the effect of new tuberculosis tests and the role of empirical treatment in real-world settings. Until such questions can be addressed, and empirical treatment is appropriately characterised, we postulate that the estimated population-level effect of new tests such as Xpert might be substantially overestimated.
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.
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
Shanks, L; Masumbuko, E W; Ngoy, N M; Maneno, M; Bartlett, S; Thi, S S; Shah, T
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.
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.
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
Mushkin, A Iu; Sovetova, N A; Alatortsev, A V; Snishchuk, V P; Nekachalova, A Z; Kovalenko, K N; Avdeeva, V G
The clinical and radiological manifestations of suboccipital tuberculosis have been analyzed in 7 patients aged 7 to 35 years. A case of this condition accompanied by extensive vertebral destruction, abscesses, and basilar impression is described in a 7.5-year-old child. A radical stabilizing operation was successfully performed using the currently available technologies.
Cegielski, J. Peter; van der Walt, Martie L.
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
Barr, David A.; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R.; Sloan, Derek J.
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
Sun, Yi-Xuan; Zhu, Lei; Lu, Zu-Hong; Jia, Zhong-Wei
Background: Migrations have been reported to be associated with the high risk of tuberculosis (TB), but there is no systematic analysis of the available data for TB among migrant in China. The aim of this study was to examine the notification rate of active and sputum smear-positive TB by a systematic review and meta-analysis. Methods: A systematic review and meta-analysis were performed to examine the notification rate of active and sputum smear-positive TB among migrants in China. Two reviewers searched the cross-sectional studies published in PubMed, EMBASE, SciFinder, and Web of Science in English and in CNKI and Wanfang databases in Chinese. Pooled estimates of notification rate of TB among migrants were calculated using a random effects model. Meta-regression analysis and subgroup analysis stratified by year, region were also performed. Results: Seventy eligible studies met the inclusion criteria for the final analysis. The overall notification rate of active TB and sputum smear-positive cases among migrants were 53.12 (95% confidence interval [CI]: 47.32–59.63) and 24.53 (95% CI: 22.01–27.34) per 100,000 populations, respectively. The notification rate of active TB significantly increased from 50.95 (95% CI: 41.11–63.14) per 100,000 populations in 2005 to 84.62 (95% CI: 78.00–91.80) per 100,000 populations in 2014 while that of smear-positive TB was constant during the study time (P = 0.79). The geographic difference was identified both for active and sputum smear-positive TB, with the higher notification rates mainly distributing along the eastern coastal areas. Conclusions: The pooled estimate of active TB and sputum smear-positive TB among migrants was lower than the national notification rate among general population, but the gap between our data and national notification rate among general population is narrowed down during 2005–2014. PMID:27453237
Carvalho, Anna C C; Migliori, Giovanni B; Cirillo, Daniela M
Tuberculosis has re-emerged as a public health concern in high-income countries in the last few decades. The European region accounts for only 5% of world TB cases. The incidence of new TB cases in Europe varies from very low rates in Scandinavian countries (six to eight cases/100,000 population) to rates as high as 231 cases/100,000 population in Tajikistan; the Russian Federation is eleventh among the 22 high-burden TB countries. The estimated detection rate of new sputum smear-positive pulmonary cases and the treatment success rate in 2007 were poor compared with other WHO regions: 51% of cases were diagnosed and 70% of them completed a full course of anti-TB therapy, which is still a long way from the World Health Assembly targets (detection of 70% of infectious cases and successful treatment of 85% of them). The low success rate is largely attributable to the increasing number of drug-resistant TB cases: Eastern European countries are among those with the highest rates of multidrug-resistant (MDR)-TB (TB resistant to rifampicin and isoniazid) in the world. By the end of September 2009, at least one case of extensively drug-resistant TB (named XDR-TB and defined as a MDR-TB strain with additional resistance to any fluoroquinolone, and to at least one of three injectable drugs used in anti-TB treatment) had been reported by 25 countries in the WHO European Region. In Western Europe, TB continues to cause disease among elderly native-born individuals, although high-risk groups including immigrants, prisoners, HIV-infected persons and drug addicts significantly contribute to the overall burden. Improved TB control in Europe requires a large coordinated effort by all stakeholders, including governments, governmental and non-governmental institutions, as well as the academic and private sectors and affected communities.
Iribarren, Sarah; Schnall, Rebecca
Tuberculosis (TB) remains a major global public health problem and is a leading killer due to an infectious disease. Mobile applications (apps) could support TB prevention and treatment. App stores were searched and of the 1332 reviewed 24 met our inclusion criteria. For each app 11 functionalities were assessed. The majority were targeted towards clinicians (n=17), few patient focused (n=4). Most had fewer than 4 functions out of 11, inform and record being the highest. Peer reviewed publications were identified for 2 of the apps and 3 apps in testing stage were found in the grey literature. Apps for TB prevention and treatment had minimal functionality, primarily targeted clinicians, and focused on information or data collection. None were for patient self-management of care and treatment or to improve patient-provider interactions. Identifying TB patient needs and involving them in the design phase is recommended.
Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ
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
Sharma, Jai Bhagwan; Sneha, J.; Singh, U. B.; Kumar, Sunesh; Roy, K. K.; Singh, Neeta; Dharmendra, Sona
AIM: To evaluate the effect of antitubercular therapy (ATT) on an ovarian function such as ovarian reserve, ovarian dimensions, and ovarian stromal blood flow. SETTINGS AND DESIGN: Prospective study design. MATERIALS AND METHODS: Fifty infertile women with female genital tuberculosis (FGTB) without tubo-ovarian masses diagnosed by positive acid-fast bacilli culture or epithelioid granuloma on endometrial aspirate or positive polymerase chain reaction with positive findings on laparoscopy or hysteroscopy were recruited. The ovarian function tests were performed on day 2/3 as follicle-stimulating hormone (FSH) levels and anti-Mullerian hormone (AMH) levels. Ovarian dimensions (length, width, and depth) were measured using a transvaginal ultrasound. Mean antral follicle count (AFC) and ovarian stromal blood flow (peak systolic velocity [PSV], pulsatility index (PI), and resistive index [RI]) were measured using a transvaginal ultrasound. All women were started on ATT for 6 months by directly observed treatment strategy. After completion of ATT, all the parameters were repeated. RESULTS: There was a significant increase in AMH (2.68 ± 0.97 ng/ml to 2.8 ± 1.03 ng/ml) pre- to post-ATT, nonsignificant increase in FSH (7.16 ± 2.34 mIU/ml to 7.26 ± 2.33 mIU/ml) post-ATT, significant increase in mean AFC (7.40 ± 2.12–8.14 ± 2.17), PSV in the right ovary (6.015–6.11 cm/s) and left ovary (6.05–6.08 cm/s), PI in the right ovary (0.935–0.951 cm/s) and left ovary (0.936–0.957 cm/s), and RI in the right ovary (0.62 ± 0.01–0.79 ± 0.02) and left ovary (0.65 ± 0.02–0.84 ± 0.01) with ATT. There was no significant change in mean ovarian dimensions (ovarian length, breadth, and width) and summed ovarian volume with ATT. On laparoscopy, tubercles were seen in 27 (54%) women. Caseous nodules and encysted ascites were seen in 8% cases each. CONCLUSION: ATT improves the ovarian function (AMH and AFC) and ovarian blood flow in women with FGTB. PMID:27803581
Via, Laura E; England, Kathleen; Weiner, Danielle M; Schimel, Daniel; Zimmerman, Matthew D; Dayao, Emmanuel; Chen, Ray Y; Dodd, Lori E; Richardson, Mike; Robbins, Katherine K; Cai, Ying; Hammoud, Dima; Herscovitch, Peter; Dartois, Véronique; Flynn, JoAnne L; Barry, Clifton E
Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated Mycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P = 0.035) and also significantly reduced uptake of [(18)F]-2-fluoro-2-deoxyglucose by positron emission tomography (P = 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P = 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation.
Jain, Paras; Thaler, David S; Maiga, Mamoudou; Timmins, Graham S; Bishai, William R; Hatfull, Graham F; Larsen, Michelle H; Jacobs, William R
The rapid and accurate diagnosis of active tuberculosis (TB) and its drug susceptibility remain a challenge. Phenotypic assays allow determination of antibiotic susceptibilities even if sequence data are not available or informative. We review 2 emerging diagnostic approaches, reporter phage and breath tests, both of which assay mycobacterial metabolism. The reporter phage signal, Green fluorescent protein (GFP) or β-galactosidase, indicates transcription and translation inside the recipient bacilli and its attenuation by antibiotics. Different breath tests assay, (1) exhaled antigen 85, (2) mycobacterial urease activity, and (3) detection by trained rats of disease-specific odor in sputum, have also been developed. When compared with culture, reporter phage assays shorten the time for initial diagnosis of drug susceptibility by several days. Both reporter phage and breath tests have promise as early markers to determine the efficacy of treatment. While sputum often remains smear and Mycobacterium tuberculosis DNA positive early in the course of efficacious antituberculous treatment, we predict that both breath and phage tests will rapidly become negative. If this hypothesis proves correct, phage assays and breath tests could become important surrogate markers in early bactericidal activity (EBA) studies of new antibiotics.
Dodor, Emmanuel Atsu; Afenyadu, Godwin Yao
The level of defaulting from treatment among tuberculosis (TB) patients at the Effia-Nkwanta Regional Hospital between January 2000 and December 2001 was 13.9%. This study was therefore designed to assess factors associated with TB treatment default and completion at the hospital. The initial part of the study consisted of three separate focus group discussions for health workers, defaulters and non-defaulters. The information collected was used to design a questionnaire that was administered to defaulters and non-defaulters selected from the Institutional TB Register. Univariate logistic regression analysis was performed to identify significant factors associated with treatment default. Statistical significance was taken as P < 0.05. Default from treatment was significantly associated with income per month (P = 0.03), ability to afford supplementary drugs (P = 0.008), availability of social support (P = 0.005) and problems relating with others while on treatment (P = 0.01). A cordial relationship between patients and health staff was the main motivating factor for completion of treatment, whilst financial difficulty was the main reason for defaulting from treatment. Determination of the characteristics found to be associated with defaulting in this study among TB patients at the start of treatment may be helpful in improving compliance among patients registered for treatment at the hospital.
Schnall, Rebecca; Stone, Patricia W; Carballo-Diéguez, Alex
Background Tuberculosis (TB) remains a major global health problem and is the leading killer due to a single infectious disease. Mobile health (mHealth)–based tools such as smartphone apps have been suggested as tools to support TB control efforts (eg, identification, contact tracing, case management including patient support). Objective The purpose of this review was to identify and assess the functionalities of mobile apps focused on prevention and treatment of TB. Methods We searched 3 online mobile app stores. Apps were included if they were focused on TB and were in English, Spanish, or Portuguese. For each included app, 11 functionalities were assessed (eg, inform, instruct, record), and searches were conducted to identify peer-review publications of rigorous testing of the available apps. Results A total of 1332 potentially relevant apps were identified, with 24 meeting our inclusion criteria. All of the apps were free to download, but 7 required login and password and were developed for specific clinics, regional sites, or research studies. Targeted users were mainly clinicians (n=17); few (n=4) apps were patient focused. Most apps (n=17) had 4 or fewer functions out of 11 (range 1-6). The most common functionalities were inform and record (n=15). Although a number of apps were identified with various functionalities to support TB efforts, some had issues such as incorrect spelling and grammar, inconsistent responses to data entry, problems with crashing, or links to features that had no data. Of more concern, some apps provided potentially harmful information to patients, such as links to natural remedies for TB and natural healers. One-third of the apps (8/24) had not been updated for more than a year and may no longer be supported. Peer-reviewed publications were identified for only two of the included apps. In the gray literature (not found in the app stores), three TB-related apps were identified as in progress, being launched, or tested. Conclusions
Frankel, Amylynne; Penrose, Carolin
Cutaneous tuberculosis occurs rarely, despite a high and increasing prevalence of tuberculosis worldwide. Mycobacterium tuberculosis, Mycobacterrium bovis, and the Bacille Calmette-Guérin vaccine can cause tuberculosis involving the skin. Cutaneous tuberculosis can be acquired exogenously or endogenously and present as a multitude of differing clinical morphologies. Diagnosis of these lesions can be difficult, as they resemble many other dermatological conditions that are often primarily considered. Further, microbiological confirmation is poor, despite scientific advances, such as the more frequent use of polymerase chain reaction. The authors report a case that illustrates the challenges faced by dermatologists when considering a diagnosis of cutaneous tuberculosis. PMID:20725570