Tuberculosis Research and Treatment The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Prevalence and Drug Resistance Patterns of Mycobacterium tuberculosis among New Smear Positive Pulmonary Tuberculosis Patients in Eastern Ethiopia Wed, 16 Apr 2014 09:36:46 +0000 The study aimed at determining the prevalence and drug resistance patterns of Mycobacterium tuberculosis among new smear positive pulmonary tuberculosis patients visiting TB diagnosis and treatment facilities at selected health facilities in eastern Ethiopia. A cross-sectional study was conducted between October 2011 and May 2013. A total of 408 new adult pulmonary TB patients (≥ 18 years) were enrolled in this study. Three consecutive sputum samples (spot, morning, and spot) were collected from each patient and transported to the Armauer Hansen Research Institute TB laboratory located in Addis Ababa for culture on Lowenstein Jensen slant media. DST was performed on 357 (87.5%) of the patient samples for isoniazid (H), rifampicin (R), ethambutol (E), and streptomycin (S) using the standard proportion method. The rate of resistance to any one drug was 23%. Any resistance to H, S, R, and E was 14%, 11.5%, 2.8%, and 0.3%, respectively. The highest proportion of monoresistance was observed against H (9.5%). MDRTB was detected in 1.1% of the patients. Any drug resistance was associated with HIV infection (COR = 3.7, 95% CI 1.905–7.222) (P = 0.000). Although the prevalence of MDRTB is relatively low in the study area, high prevalence of H resistance is a serious concern demanding close monitoring. Expanding diagnostic capacity for mycobacterial culture and DST is a vital step in this regard. Berhanu Seyoum, Meaza Demissie, Alemayehu Worku, Shiferaw Bekele, and Abraham Aseffa Copyright © 2014 Berhanu Seyoum et al. All rights reserved. Seasonality of Tuberculosis in Delhi, India: A Time Series Analysis Sun, 23 Mar 2014 12:39:28 +0000 Background. It is highly cost effective to detect a seasonal trend in tuberculosis in order to optimize disease control and intervention. Although seasonal variation of tuberculosis has been reported from different parts of the world, no definite and consistent pattern has been observed. Therefore, the study was designed to find the seasonal variation of tuberculosis in Delhi, India. Methods. Retrospective record based study was undertaken in a Directly Observed Treatment Short course (DOTS) centre located in the south district of Delhi. Six-year data from January 2007 to December 2012 was analyzed. Expert modeler of SPSS ver. 21 software was used to fit the best suitable model for the time series data. Results. Autocorrelation function (ACF) and partial autocorrelation function (PACF) at lag 12 show significant peak suggesting seasonal component of the TB series. Seasonal adjusted factor (SAF) showed peak seasonal variation from March to May. Univariate model by expert modeler in the SPSS showed that Winter’s multiplicative model could best predict the time series data with 69.8% variability. The forecast shows declining trend with seasonality. Conclusion. A seasonal pattern and declining trend with variable amplitudes of fluctuation were observed in the incidence of tuberculosis. Varun Kumar, Abhay Singh, Mrinmoy Adhikary, Shailaja Daral, Anita Khokhar, and Saudan Singh Copyright © 2014 Varun Kumar et al. All rights reserved. Acceptance of Provider Initiated HIV Testing and Counseling among Tuberculosis Patients in East Wollega Administrative Zone, Oromia Regional State, Western Ethiopia Thu, 20 Mar 2014 11:44:36 +0000 Human immunodeficiency virus (HIV) is a powerful risk factor for the development of tuberculosis. This study assessed the acceptance and associated factors that can affect provider initiated HIV testing and counseling (PITC) among tuberculosis patients at the East Wollega administrative zone, Oromia regional state, western Ethiopia, from January to August, 2010. A single population proportion formula is used to calculate the total sample size of 406 and the cluster sampling technique was used to select 13 health centers that provide PITC services. The sample size was proportionally allocated to each health center. The study participants were selected using a simple random sampling technique using the lottery method. Structured questionnaire was used for collection of sociodemographic data. From the total of study subjects, 399 (98.2%) TB patients were initiated for HIV test and 369 (92.5%) patients accepted the initiation. Of those, 353 (95.5%) patients had taken HIV test and received their results. According to the reviewed documents, the prevalence of HIV among tuberculosis (TB) patients in the study area was 137 (33.7%). The logistic regression result showed the PITC was significantly associated with their knowledge about HIV (AOR = 3.22, 95% CI: 1.3–7.97), self-perceived risk (AOR = 2.93, 95% CI: 1.12–7.66), educational status (AOR = 3.51, 95% CI: 1.13–10.91), and knowledge on transmission of HIV/AIDS (AOR = 7.56, 95% CI: 1.14–40.35) which were significantly associated with the acceptance of PITC among TB patients. Therefore, this study’s results showed, the prevalence of HIV among TB patient was high; to enhance the acceptance of PITC among TB patients, health extension workers must provide health education during home-to-home visiting. TB treatment supervisors also provide counseling intensively for all forms of TB patients during their first clinical encounter. Wakjira Kebede, Fikru Keno, Temesgen Ewunetu, and Gutu Mamo Copyright © 2014 Wakjira Kebede et al. All rights reserved. Tuberculin Skin Tests versus Interferon-Gamma Release Assays in Tuberculosis Screening among Immigrant Visa Applicants Thu, 06 Mar 2014 15:58:33 +0000 Objective. Use of tuberculin skin tests (TSTs) and interferon gamma release assays (IGRAs) as part of tuberculosis (TB) screening among immigrants from high TB-burden countries has not been fully evaluated. Methods. Prevalence of Mycobacterium tuberculosis infection (MTBI) based on TST, or the QuantiFERON-TB Gold test (QFT-G), was determined among immigrant applicants in Vietnam bound for the United States (US); factors associated with test results and discordance were assessed; predictive values of TST and QFT-G for identifying chest radiographs (CXRs) consistent with TB were calculated. Results. Of 1,246 immigrant visa applicants studied, 57.9% were TST positive, 28.3% were QFT-G positive, and test agreement was 59.4%. Increasing age was associated with positive TST results, positive QFT-G results, TST-positive but QFT-G-negative discordance, and abnormal CXRs consistent with TB. Positive predictive values of TST and QFT-G for an abnormal CXR were 25.9% and 25.6%, respectively. Conclusion. The estimated prevalence of MTBI among US-bound visa applicants in Vietnam based on TST was twice that based on QFT-G, and 14 times higher than a TST-based estimate of MTBI prevalence reported for the general US population in 2000. QFT-G was not better than TST at predicting abnormal CXRs consistent with TB. Stella O. Chuke, Nguyen Thi Ngoc Yen, Kayla F. Laserson, Nguyen Huu Phuoc, Nguyen An Trinh, Duong Thi Cam Nhung, Vo Thi Chi Mai, An Dang Qui, Hoang Hoa Hai, Le Thien Huong Loan, Warren G. Jones, William C. Whitworth, J. Jina Shah, John A. Painter, Gerald H. Mazurek, and Susan A. Maloney Copyright © 2014 Stella O. Chuke et al. All rights reserved. Performance of Tuberculin Skin Test Measured against Interferon Gamma Release Assay as Reference Standard in Children Mon, 10 Feb 2014 08:23:42 +0000 Objectives. International guidelines differ in the threshold of tuberculin skin test (TST) induration regarded as indicating Mycobacterium (M.) tuberculosis infection. Interferon gamma release assay (IGRA) results were used as reference to assess performance of TST induration thresholds for detection of M. tuberculosis infection in children. Design. Systematic review which included studies containing data on TST, IGRA, and Bacillus Calmette-Guérin (BCG) status in children. Data bases searched were PubMed, EMBASE, and the Cochrane library. Specificities and sensitivities were calculated for TST thresholds 5, 10, and 15 mm and correlated with age and geographical latitude. Results. Eleven studies with 2796 children were included. For BCG immunised children diameters of 5, 10, and 15 mm had median sensitivities of 87, 70, and 75% and specificities of 67, 93, and 90%, respectively. In non-BCG immunised children median sensitivities were 94, 95, and 83% and specificities 91, 95, and 97%. At the 10 mm threshold age correlated negatively with sensitivity of TST (, ) and latitude correlated positively (, ). Conclusions. For the 10 mm threshold the sensitivity of the TST is lower in BCG immunised children. Younger age and higher geographical latitude were associated with higher sensitivity of the TST. Michael Eisenhut and Katy Fidler Copyright © 2014 Michael Eisenhut and Katy Fidler. All rights reserved. Quality of Tuberculosis Care in Private Health Facilities of Addis Ababa, Ethiopia Wed, 29 Jan 2014 00:00:00 +0000 Ensuring provision of good quality tuberculosis (TB) care, especially in private for profit health facilities, is an important component of TB control strategy to reduce poor medical practice which results in multidrug resistant TB (MDR-TB). The aim of this study was to investigate quality of TB care in private health facilities of Addis Ababa. A facility based cross-sectional study was conducted based on Donabedian’s structure-process-outcome model of health care quality. Quality of care was determined by adherence to National TB Program guidelines, treatment success rate, and client satisfaction. Exit interview was conducted on 292 patients on the intensive phase of treatment and 384 patient records were reviewed in eight private health facilities. Initial diagnostic AFB test was done for 95.4% of pulmonary TB patients. Most important components of TB care recommended by national guidelines were delivered for a significant proportion of patients. Majority (75%) of the clients were found to be satisfied with each component of TB care. The treatment success rate was 90.9%. The quality of TB care was fairly good. However, only 77.7% of the patients were counseled for HIV testing. Strengthening HIV counseling and testing, tackling shortage of streptomycin and laboratory reagent at private TB clinic is crucial. Gezahegn Gebrekidan, Gezahegn Tesfaye, Mitiku Teshome Hambisa, and Negussie Deyessa Copyright © 2014 Gezahegn Gebrekidan et al. All rights reserved. Application of Cox Proportional Hazards Model in Case of Tuberculosis Patients in Selected Addis Ababa Health Centres, Ethiopia Sun, 12 Jan 2014 16:54:09 +0000 Introduction. Tuberculosis (TB) is a chronic infectious disease and mainly caused by mycobacterium tuberculosis (MTB). It has been one of the major causes of mortality in Ethiopia. The objective of the study was to identify factors that affect the survival of the patients with tuberculosis who started treatment for tuberculosis. Methods. This was a retrospective study in six randomly selected health centres in Addis Ababa, Ethiopia. The data were obtained from medical records of TB patients registered from September 2012 to August 2013 and treated under directly observed treatment surgery (DOTS) strategy. Kaplan Meier plots, logrank tests, and Wilcoxon tests were used to assess the survival pattern. Cox proportional hazards model for multivariable analysis was discussed. Results. Out of the total 826 registered TB patients, 105 (12.71%) died during the study period and 712 (87.29%) were censored. Based on Kaplan Meier survival curves, logrank test, and Wilcoxon test, it was found that the patients had statistically significant differences in survival experience with respect to age, body weight at initiation of treatment, TB patient category, and HIV status. Multivariable Cox hazards regression analysis revealed that the covariates age, TB patient category, HIV, and age by HIV interaction were significant risk factors associated with death status in TB patients. Conclusion. Deaths of individuals with diseases especially HIV coinfected and nonnew TB cases were high. Therefore, this needs to strengthen the follow-up of patients with TB treatment from the day of anti-TB treatment initiation to completion days. Kabtamu Tolosie and M. K. Sharma Copyright © 2014 Kabtamu Tolosie and M. K. Sharma. All rights reserved. Histopathological Findings in Immunohistological Staining of the Granulomatous Tissue Reaction Associated with Tuberculosis Sun, 05 Jan 2014 10:24:34 +0000 Purpose. The histological diagnosis of Mycobacterium tuberculosis (MTB) remains a diagnostic challenge despite different methods. Immunohistochemistry (IHC) not only could confirm granulomatous tissue involvement but also can demonstrate MTB antigen immunolocalization. This study tries to clarify the details of immunohistochemical staining for MTB with pAbBCG. Materials/Methods. Twenty-three confirmed TB granulomatous tissue samples were studied by Ziehl-Neelsen and immunohistochemistry (IHC) staining with pAbBCG. Samples were selected from the archive of the Department of Pathology, National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran. Results. IHC staining was positive in all samples, whereas Ziehl-Neelsen was positive in 9 cases out of 23 (39.1%). Tissue types used were pleural tissue, lymph nodes, and lung tissue. IHC showed positive coarse granular cytoplasmic and round, fragmented bacillary staining. In this study, epithelioid cells clearly showed more positive staining at the periphery of the granuloma rather than the center of granuloma. There is also positive staining in endothelial cells, fibroblasts, plasma cells, lymphocytes, and macrophages outside the granuloma. Conclusion. Considering the criteria of positive immunohistochemical staining of TB granulomatous reactions, this stain not only highlights the presence of mycobacterial antigens for tissue diagnosis, but also could morphologically localize its distribution in different cells. Shirin Karimi, Masoud Shamaei, Mihan Pourabdollah, Makan Sadr, Mehrdad Karbasi, Arda Kiani, and Moslem Bahadori Copyright © 2014 Shirin Karimi et al. All rights reserved. Nontuberculous Mycobacteria in Guadeloupe, Martinique, and French Guiana from 1994 to 2012 Wed, 18 Dec 2013 10:44:02 +0000 Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms able to cause severe opportunistic human infections. Their distribution patterns are subject to geographical variations. This study describes their isolation frequencies from clinical specimen in the three French overseas departments of the Americas, namely, Guadeloupe, Martinique, and French Guiana during 1994–2012. A total of 651 strains from as many patients (one isolate per species per patient) were analysed regarding regional isolation patterns and potential pattern changes over time. The Mycobacterium avium complex was the most common group of NTM in Guadeloupe and French Guiana. In Martinique it was the second most common after the rapidly growing mycobacteria. M. fortuitum was the most commonly isolated species in all three departments. Some species (M. kansasii, M. xenopi, and M. terrae complex) displayed a clear regional preference. Furthermore a change in isolation frequency was observed for M. intracellulare (increase) and M. kansasii (decrease) in Guadeloupe. In conclusion, marked regional differences in isolation frequencies of NTM species were observed in the study area. Results are discussed in context of variables such as study populations, risk factors, methodology employed, isolation from pulmonary versus sterile isolation sites (blood, urine, and CSF), and in vitro drug-susceptibility patterns. Elisabeth Streit, Julie Millet, and Nalin Rastogi Copyright © 2013 Elisabeth Streit et al. All rights reserved. TextTB: A Mixed Method Pilot Study Evaluating Acceptance, Feasibility, and Exploring Initial Efficacy of a Text Messaging Intervention to Support TB Treatment Adherence Thu, 12 Dec 2013 08:26:06 +0000 Objective. To assess a text messaging intervention to promote tuberculosis (TB) treatment adherence. Methods. A mixed-methods pilot study was conducted within a public pulmonary-specialized hospital in Argentina. Patients newly diagnosed with TB who were 18 or older, and had mobile phone access were recruited and randomized to usual care plus either medication calendar () or text messaging intervention () for the first two months of treatment. Primary outcomes were feasibility and acceptability; secondary outcomes explored initial efficacy. Results. Feasibility was evidenced by high access to mobile phones, familiarity with texting, most phones limited to basic features, a low rate of participant refusal, and many describing suboptimal TB understanding. Acceptability was evidenced by participants indicating feeling cared for, supported, responsible for their treatment, and many self-reporting adherence without a reminder. Participants in the texting group self-reported adherence on average 77% of the days whereas only 53% in calendar group returned diaries. Exploring initial efficacy, microscopy testing was low and treatment outcomes were similar in both groups. Conclusion. The texting intervention was well accepted and feasible with greater reporting of adherence using text messaging than the diary. Further evaluation of the texting intervention is warranted. Sarah Iribarren, Susan Beck, Patricia F. Pearce, Cristina Chirico, Mirta Etchevarria, Daniel Cardinale, and Fernando Rubinstein Copyright © 2013 Sarah Iribarren et al. All rights reserved. Perspectives of Stakeholders on the Sustainability of Tuberculosis Control Programme in Ghana Thu, 28 Nov 2013 16:52:32 +0000 Objectives. To solicit the views of some key stakeholders involved in TB control in Ghana on the sustainability of the current programme and corresponding interventions and to further discuss these views in the context of improving and/or ensuring the sustainability of existing interventions and structures. Methods. The study employed an interpretivist (qualitative) approach in order to obtain the “lived” experiences of personnel who are involved in TB control, either directly or indirectly. Purposive sampling was applied to select 19 respondents who provided data for the study through in-depth interviews (IDIs). The IDI data was analysed inductively in a progressive manner. Thus, respective codes were allowed to emerge from the data as opposed to deductive coding where themes are precoded. Results. The findings reveal two main strands of views about the sustainability of the current TB control programmes: optimism and pessimism. The optimists revealed that the integration of TB into the generalised health system, integration of TB and HIV control services, the use of internally generated funds of health facilities, and a general improvement in socioeconomic conditions of the general population could provide positive pathways to sustainability. The pessimists on the other hand noted that the existing programme was not likely to be sustainable so long as much of the operational funds were derived from external sources. Largely, the views of the pessimists were influenced by their past experiences in TB control. Conclusions. This paper has shown both opportunities and threats to sustainability of TB control in Ghana. The opportunities and threats could be managed positively depending on how policy actors respond to the issues raised. Joshua Amo-Adjei Copyright © 2013 Joshua Amo-Adjei. All rights reserved. Pastoralist Community’s Perception of Tuberculosis: A Quantitative Study from Shinille Area of Ethiopia Wed, 27 Nov 2013 10:31:38 +0000 Background. In Ethiopia the prevalence of all forms of TB is estimated at 261/100 000 population, leading to an annual mortality rate of 64/100 000 population. The incidence rate of smear-positive TB is 108/100 000 population. Objectives. To assess knowledge, attitudes, and practices regarding TB among pastoralists in Shinille district, Somali region, Ethiopia. Method. A community-based cross-sectional study was conducted among 821 pastoralists aged >18 years and above from February to May, 2011 using self-structured questionnaire. Results. Most (92.8%) of the study participants heard about TB, but only 10.1% knew about its causative agent. Weight loss as main symptom, transmittance through respiratory air droplets, and sputum examination for diagnosis were the answers of 34.3%, 29.9%, and 37.9% of pastoralists, respectively. The majority (98.3%) of respondents reported that TB could be cured, of which 93.3% believed with modern drugs. About 41.3% of participants mentioned covering the nose and mouth during sneezing and coughing as a preventive measure. The multivariate logistic regression analysis indicated that household income >300 Ethiopian Birr and Somali ethnicity were associated with high TB knowledge. Regarding health seeking behaviour practice only 48.0% of the respondents preferred to visit government hospital and discuss their problems with doctors/health care providers. Conclusion. This study observed familiarity with gaps and low overall knowledge on TB and revealed negative attitudes like discrimination intentions in the studied pastoral community. Samuel Melaku, Hardeep Rai Sharma, and Getahun Asres Alemie Copyright © 2013 Samuel Melaku et al. All rights reserved. Early Therapeutic Drug Monitoring for Isoniazid and Rifampin among Diabetics with Newly Diagnosed Tuberculosis in Virginia, USA Sun, 17 Nov 2013 09:45:26 +0000 Slow responders to tuberculosis (TB) treatment in Virginia have prolonged treatment duration and consume more programmatic resources. Diabetes is an independent risk factor for slow response and low serum anti-TB drug concentrations. Thus, a statewide initiative of early therapeutic drug monitoring (TDM) for isoniazid and rifampin at 2 weeks after TB treatment was piloted for all diabetics with newly diagnosed TB. During the period of early TDM, 12/01/2011–12/31/2012, 21 diabetics had concentrations performed and 16 (76%) had a value below the expected range for isoniazid, rifampin, or both. Fifteen had follow-up concentrations after dose adjustment and 12 (80%) increased to within the expected range (including all for rifampin). Of 16 diabetic patients with pulmonary TB that had early TDM, 14 (88%) converted their sputum culture to negative in <2 months. Early TDM for diabetics was operationally feasible, may speed response to TB therapy, and can be considered for TB programs with high diabetes prevalence. Scott K. Heysell, Jane L. Moore, Debbie Staley, Denise Dodge, and Eric R. Houpt Copyright © 2013 Scott K. Heysell et al. All rights reserved. Drug Resistance Pattern of MTB Isolates from PTB Patients Thu, 24 Oct 2013 17:06:02 +0000 Background. TB is a global pandemic disease. All TB control programs were not successful due to the emergence of multidrug resistance in M. tuberculosis strains. Objective of the present study was to detect the rate of MDR-MTB in this part of India. Methods. One hundred and thirty clinical MTB strains isolated from patients on treatment and confirmed as MTB by MPT64 antigen detection were tested for drug susceptibility against Streptomycin, INH, Rifampicin, and Ethambutol by MBBact automated system. Result. Thirty-two were MDRs (25.61%). 31.2%, 28%, 17.6%, and 21.6% were resistant to INH, RIF, Ethambutol, and Streptomycin, respectively. Resistance to either INH or Rifampicin was 20.8% and 13.88%, respectively. Combined INH and Rifampicin resistance was seen in 18.05% isolates. Conclusion. Drug resistance rate is high in patients treated previously and who have been irregular on treatment. Rajani Ranganath, Vijay G. S. Kumar, Ravi Ranganath, Gangadhar Goud, and Veerabhadra Javali Copyright © 2013 Rajani Ranganath et al. All rights reserved. Initial Antituberculous Regimen with Better Drug Penetration into Cerebrospinal Fluid Reduces Mortality in HIV Infected Patients with Tuberculous Meningitis: Data from an HIV Observational Cohort Study Mon, 12 Aug 2013 11:39:11 +0000 Tuberculous meningitis (TM) is the deadliest form of tuberculosis. Nearly two-thirds of HIV infected patients with TM die, and most deaths occur within one month. Current treatment of TM involves the use of drugs with poor penetration into the cerebro-spinal fluid (CSF). In this study, we present the mortality before and after implementing a new antituberculous regimen (ATR) with a higher drug penetration in CSF than the standard ATR during the initial treatment of TM in an HIV cohort study. The new ATR included levofloxacin, ethionamide, pyrazinamide, and a double dose of rifampicin and isoniazid and was given for a median of 7 days (interquartile range 6–9). The new ATR was associated with an absolute 21.5% (95% confidence interval (CI), 7.3–35.7) reduction in mortality at 12 months. In multivariable analysis, independent factors associated with mortality were the use of the standard ATR versus the new ATR (hazard ratio 2.05; 95% CI, 1.2–3.5), not being on antiretroviral therapy, low CD4 lymphocyte counts, and low serum albumin levels. Our findings suggest that an intensified initial ATR, which likely results in higher concentrations of active drugs in CSF, has a beneficial effect on the survival of HIV-related TM. Gerardo Alvarez-Uria, Manoranjan Midde, Raghavakalyan Pakam, and Praveen Kumar Naik Copyright © 2013 Gerardo Alvarez-Uria et al. All rights reserved. Mycobacterial Etiology of Pulmonary Tuberculosis and Association with HIV Infection and Multidrug Resistance in Northern Nigeria Tue, 16 Jul 2013 12:44:04 +0000 Objective. Data on pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) complex in Nigeria are limited. We investigated species of MTB complex in TB cases from northern Nigeria. Methods. New TB suspects were enrolled, screened for HIV and their sputum samples were cultured after routine microscopy. Genotypes MTBC and MTBDRplus were used to characterize the MTB complex species and their resistance to isoniazid and rifampicin. Results. Of the 1,603 patients enrolled, 375 (23%) had MTB complex infection: 354 (94.4%) had Mycobacterium tuberculosis; 20 (5.3%) had Mycobacterium africanum; and one had Mycobacterium bovis (0.3%). Cases were more likely to be male (AOR = 1.87, 95% CI : 1.42–2.46; ), young (AOR = 2.03, 95% CI : 1.56–2.65; ) and have HIV (AOR = 1.43, 95% CI : 1.06–1.92; ). In 23 patients (6.1%), the mycobacterium was resistant to at least one drug, and these cases were more likely to have HIV and prior TB treatment (AOR = 3.62, 95% CI : 1.51–8.84; ; AOR : 4.43; 95% CI : 1.71–11.45 resp.), compared to cases without any resistance. Conclusion. Mycobacterium tuberculosis remained the predominant specie in TB in this setting followed by Mycobacterium africanum while Mycobacterium bovis was rare. The association of TB drug resistance with HIV has implications for TB treatment. Gambo Aliyu, Samer S. El-Kamary, Alash'le Abimiku, Nicholas Ezati, Iwakun Mosunmola, Laura Hungerford, Clayton Brown, Kathleen J. Tracy, Joshua Obasanya, and William Blattner Copyright © 2013 Gambo Aliyu et al. All rights reserved. Immunisation with BCG in the Maringue District, Sofala Province, Mozambique Tue, 30 Apr 2013 10:43:41 +0000 Objectives. We evaluated immunisation with Bacille Calmette-Guérin (BCG) among newborns in 2011 in the Maringue District, Sofala Province, Mozambique, which includes seven health units. The study was motivated by the fact that in official reports, immunisation coverage was unreliable (more than 100%). Methods. The office of maternal-child health of the central Maringué-Sede health unit provided the number of live newborns in 2011 at the maternal clinics of the seven health units and an estimate of the number of home deliveries. From vaccination registers, we abstracted records of BCG vaccinations administered in the period 01/01/2011–30/06/2012 to children born in 2011. Results. The number of live newborns was 3,353. Overall, the number of BCG vaccinations administered was 2,893, with a coverage of 86.3%. Conclusion. In this study, we could only calculate an approximate coverage estimate, because of unavailability of adequate individual information. Recording practices should be changed in order to allow use of individual information and linkage across different information sources and thus a more precise vaccination coverage assessment. Dario Consonni, Marina Margarida Montenegro Agorostos Karagianis, and Giuseppe Bufardeci Copyright © 2013 Dario Consonni et al. All rights reserved. Psychiatric Morbidity and Other Factors Affecting Treatment Adherence in Pulmonary Tuberculosis Patients Mon, 15 Apr 2013 13:47:13 +0000 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. Argiro Pachi, Dionisios Bratis, Georgios Moussas, and Athanasios Tselebis Copyright © 2013 Argiro Pachi et al. All rights reserved. Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis Thu, 28 Mar 2013 15:24:20 +0000 Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μg/mL of moxifloxacin; 93.6%, 1.0 μg/mL of levofloxacin; 97.5%, 2.5 μg/mL of kanamycin; 90.6%, 2.5 μg/mL of capreomycin; 86.2%, 5.0 μg/mL of ethionamide; and 90.8%, 2.0 μg/mL of -aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ-aminosalicylic acid is required. Hyejin Kim, Minji Seo, Young Kil Park, Jae-Il Yoo, Yeong Seon Lee, Gyung Tae Chung, and Sungweon Ryoo Copyright © 2013 Hyejin Kim et al. All rights reserved. Cytokine Polymorphisms, Their Influence and Levels in Brazilian Patients with Pulmonary Tuberculosis during Antituberculosis Treatment Sun, 24 Mar 2013 18:08:53 +0000 Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify if IFNG, IL12B, TNF, IL17A, IL10, and TGFB1 gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB) at different time points of antituberculosis treatment (T1, T2, and T3). Our results showed the following associations: IFNG +874 T allele and IFNG +2109 A allele with higher IFN-γ levels; IL12B +1188 C allele with higher IL-12 levels; TNF −308 A allele with higher TNF-α plasma levels in controls and mRNA levels in PTB patients at T1; IL17A A allele at rs7747909 with higher IL-17 levels; IL10 −819 T allele with higher IL-10 levels; and TGFB1 +29 CC genotype higher TGF-β plasma levels in PTB patients at T2. The present study suggests that IFNG +874T/A, IFNG +2109A/G, IL12B +1188A/C, IL10 −819C/T, and TGFB1 +21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment. Eliana Peresi, Larissa Ragozo Cardoso Oliveira, Weber Laurentino da Silva, Érika Alessandra Pellison Nunes da Costa, João Pessoa Araujo Jr., Jairo Aparecido Ayres, Maria Rita Parise Fortes, Edward A. Graviss, Ana Carla Pereira, and Sueli Aparecida Calvi Copyright © 2013 Eliana Peresi et al. All rights reserved. Design of Thymidine Analogues Targeting Thymidilate Kinase of Mycobacterium tuberculosis Sun, 24 Mar 2013 13:18:42 +0000 We design here new nanomolar antituberculotics, inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt), by means of structure-based molecular design. 3D models of TMPKmt-inhibitor complexes have been prepared from the crystal structure of TMPKmt cocrystallized with the natural substrate deoxythymidine monophosphate (dTMP) (1GSI) for a training set of 15 thymidine analogues (TMDs) with known activity to prepare a QSAR model of interaction establishing a correlation between the free energy of complexation and the biological activity. Subsequent validation of the predictability of the model has been performed with a 3D QSAR pharmacophore generation. The structural information derived from the model served to design new subnanomolar thymidine analogues. From molecular modeling investigations, the agreement between free energy of complexation () and values explains 94% of the TMPKmt inhibition () by variation of the computed and 92% for the pharmacophore (PH4) model (). The analysis of contributions from active site residues suggested substitution at the 5-position of pyrimidine ring and various groups at the 5′-position of the ribose. The best inhibitor reached a predicted of 0.155 nM. The computational approach through the combined use of molecular modeling and PH4 pharmacophore is helpful in targeted drug design, providing valuable information for the synthesis and prediction of activity of novel antituberculotic agents. Luc Calvin Owono Owono, Melalie Keita, Eugene Megnassan, Vladimir Frecer, and Stanislav Miertus Copyright © 2013 Luc Calvin Owono Owono et al. All rights reserved. Active Case Finding of Pulmonary Tuberculosis through Screening of Respiratory Symptomatics Using Sputum Microscopy: Is It Time to Change the Paradigm? Thu, 28 Feb 2013 09:50:22 +0000 Background. One of the main strategies for the early detection of pulmonary tuberculosis (PTB) is through the screening of individuals with symptoms compatible with PTB. Although this is programmatic strategy for active case finding, its yield is not well known. Objective. To determine the yield of pulmonary tuberculosis active case finding through the screening of respiratory symptomatic (RS) patients at a general hospital. Methods. RS patients were defined as subjects complaining of cough and/or sputum for a period of 2 or more weeks. Outpatients and their companions were approached while they waited in the outpatient care areas of the hospital to detect RS. Two samples from different days or 2 samples taken 2 hours apart on the same day were collected. Results. 122 RS patients were identified. Fifty-seven patients (46.7%) had at least one sputum sample analyzed. Three patients presented a positive smear and 2 were culture positive; neither had upper airway symptoms. None of the patients with productive cough and upper airway symptoms had a positive smear (). Only 19 (33.3%) returned to the laboratory to retrieve their results. Conclusion. Current strategy to screen RS patients based only on clinical data has a low compliance. Specific strategies to increase compliance (removal of barriers, incentives, etc.) should be implemented. Eva Carolina del Portillo-Mustieles and Rafael Laniado-Laborín Copyright © 2013 Eva Carolina del Portillo-Mustieles and Rafael Laniado-Laborín. All rights reserved. The Effect of Low CD4+ Lymphocyte Count on the Radiographic Patterns of HIV Patients with Pulmonary Tuberculosis among Nigerians Wed, 30 Jan 2013 11:31:07 +0000 Objective. To assess the radiographic features in patients with Human Immunodeficiency Virus (HIV) complicated by pulmonary tuberculosis (PTB), and the association with CD4 lymphocyte count and sputum smear. Method. A prospective study was carried out on 89 HIV positive patients with PTB. The demographics, smoking history, sputum smear result, chest radiographic findings and CD4 lymphocyte count were documented. Results. Out of the 89 patients recruited in the study, 41 were males and 48 were females. Eighteen (18) patients had typical radiographic features, 60 patients had atypical radiographic features while only 11 of them had normal radiographic films. Sixty eight (68) patients had CD4 count <200 cells/mm3, 19 patients had CD4 count between 200–499 cells/mm3, while only 2 patients had CD4 count from 500 cells/mm3 upwards. The association between low CD4 count and radiographic finding was statistically significant, ( value ). Sixty (60) patients had negative sputum smear for Acid and Alcohol Fast Bacilli (AAFB), while the remaining 29 patients had positive smear. The association between low CD4 count and negative smear was statistically significant ( value ). Conclusion. The radiographic pattern and the result of the sputum smear for AAFB has a significant relationship and association with the immune status of patients with Human Immunodeficiency Virus (HIV) complicated by pulmonary tuberculosis. Christopher Affusim, Vivien Abah, Emeka B. Kesieme, Kester Anyanwu, Taofik A. T. Salami, and Reuben Eifediyi Copyright © 2013 Christopher Affusim et al. All rights reserved. Awareness of the Warning Signs, Risk Factors, and Treatment for Tuberculosis among Urban Nigerians Mon, 14 Jan 2013 14:10:55 +0000 Objectives. To determine the awareness of the warning signs, risk factors, and treatment of tuberculosis among urban Nigerians. Methods. This was a cross-sectional survey among 574 adults in Ilorin, Nigeria. Semistructured questionnaire was administered by trained interviewers to obtain information about awareness of tuberculosis warning signs, risk factors, and treatment. Results. Majority of the subjects (71.4%) were aware of at least one warning sign of tuberculosis. Cough (66.2%), weight loss (38.0%), and haemoptysis (30.7%) were the most identified warning signs. The predictors of awareness of warning sign were increasing age (), higher family income (), higher level of education (), and belonging to Christian faith (). Awareness of risk factors for tuberculosis was higher for tobacco smokers (77.0%) and history of contact with a case of TB (76.0%). Less than half were aware of HIV infection (49.8%), alcohol consumption (42.5%), chronic kidney disease (40.4%), extremes of ages (39.4%), cancers (36.9%), and diabetes mellitus (27.5%) as risk factors for TB. Tuberculosis was reported to be curable by 74.6% of the subjects and 67.9% knew that there are medications for treatment of tuberculosis, while 11.5% knew the duration of treatment. Conclusion. This study has revealed that the awareness of HIV and noncommunicable diseases as risk factors for TB is poor. This study has therefore demonstrated the need for health education programs that will emphasize recognition, identification, and modification of risk factor for TB. Olufemi O. Desalu, Adekunle O. Adeoti, Abayomi Fadeyi, Alakija K. Salami, Ademola E. Fawibe, and Olanrewaju O. Oyedepo Copyright © 2013 Olufemi O. Desalu et al. All rights reserved. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study Thu, 10 Jan 2013 16:16:12 +0000 Background: our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. Methods: we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. Results: 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1–5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). Conclusions: cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population. Christopher Vinnard, Anand Gopal, Darren R. Linkin, and Joel Maslow Copyright © 2013 Christopher Vinnard et al. All rights reserved. Can Social History Variables Predict Prison Inmates’ Risk for Latent Tuberculosis Infection? Sun, 23 Dec 2012 11:43:31 +0000 Improved screening and treatment of latent tuberculosis infection (LTBI) in correctional facilities may improve TB control. The Ohio Department of Rehabilitation and Correction (ODRC) consists of 32 prisons. Inmates are screened upon entry to ODRC and yearly thereafter. The objective of the study was to determine if social history factors such as tobacco, alcohol, and drug use are significant predictors of LTBI and treatment outcomes. We reviewed the medical charts of inmates and randomly selected age-matched controls at one ODRC facility for 2009. We used a conditional logistic regression to assess associations between selected social history variables and LTBI diagnosis. Eighty-nine inmates with a history of LTBI and 88 controls were identified. No social history variable was a significant predictor of LTBI. Medical comorbidities such as asthma, rheumatoid arthritis, and hepatitis C were significantly higher in inmates with LTBI. 84% of inmates diagnosed with LTBI had either completed or were on treatment. Annual TB screening may not be cost-effective in all inmate populations. Identification of factors to help target screening populations at risk for TB is critical. Social history variables did not predict LTBI in our inmate population. Additional studies are needed to identify inmates for the targeted TB testing. Tyler E. Weant, Abigail Norris Turner, Maureen Murphy-Weiss, David M. Murray, and Shu-Hua Wang Copyright © 2012 Tyler E. Weant et al. All rights reserved. Intestinal/Peritoneal Tuberculosis in Children: An Analysis of Autopsy Cases Wed, 19 Dec 2012 08:55:13 +0000 Infection by Mycobacterium bovis is not infrequently identified in Mexico. Its relation to nonpasteurized milk products ingestion is well recognized with primary infection usually in the intestinal tract. The term “abdominal tuberculosis” includes peritoneal as well as primary and secondary intestinal tuberculosis. The clinical differentiation of these conditions is difficult. In this work, we reviewed the clinical and pathological features of 24 cases of children dying with tuberculosis in whom autopsy revealed abdominal disease in a referral hospital in Mexico City. We identified 8 cases of primary intestinal tuberculosis, with documentation of M. bovis in 6 of them, and 9 cases of secondary intestinal tuberculosis (primary pulmonary disease), all negative to M. bovis. Seven patients had peritoneal tuberculosis without intestinal lesions and with active pulmonary disease in 4 of them, and of the remaining three, two had mesenteric lymph node involvement suggesting healed intestinal disease. In this approach to abdominal tuberculosis, postmortem analysis was able to differentiate primary from secondary intestinal tuberculosis and to define the nature of peritoneal involvement. This discrimination gives rise to different diagnostic approaches and epidemiological and preventive actions, particularly in countries where tuberculosis is endemic and infection by M. bovis continues to be identified. Cecilia Ridaura-Sanz, Eduardo López-Corella, and Ruy Lopez-Ridaura Copyright © 2012 Cecilia Ridaura-Sanz et al. All rights reserved. Tuberculosis Diagnostics in the New Millennium: Role in TB Identification and Control Tue, 18 Dec 2012 15:29:35 +0000 Soumitesh Chakravorty, Catharina Boehme, and Jongseok Lee Copyright © 2012 Soumitesh Chakravorty et al. All rights reserved. Soluble Urokinase Plasminogen Activator Receptor Levels in Tuberculosis Patients at High Risk for Multidrug Resistance Thu, 13 Dec 2012 10:06:05 +0000 The soluble urokinase plasminogen activator receptor (suPAR) has been shown to be a strong prognostic biomarker for tuberculosis (TB). In the present study, the profiles of plasma suPAR levels in pulmonary TB patients at high risk for multidrug resistance were analyzed and compared with those in multidrug resistant (MDR)-TB patients. Forty patients were prospectively included, consisting of 10 MDR-TB patients and 30 TB patients at high risk for MDR, underwent clinical assesment. Plasma suPAR levels were measured using ELISA (SUPARnostic, Denmark) and bacterial cultures were performed in addition to drug susceptibility tests. All patients of suspected MDR-TB group demonstrated significantly higher suPAR levels compared with the healthy TB-negative group (1.79 ng/mL). Among the three groups at high risk for MDR-TB, only the relapse group (7.87 ng/mL) demonstrated suPAR levels comparable with those of MDR-TB patients (7.67 ng/mL). suPAR levels in the two-month negative acid-fast bacilli conversion group (9.29 ng/mL) were higher than positive control, whereas levels in the group consisting of therapy failure patients (5.32 ng/mL) were lower. Our results strongly suggest that suPAR levels enable rapid screening of suspected MDR-TB patients, but cannot differentiate between groups. Tri Yudani Mardining Raras, Triwahju Astuti, and Iin Noor Chozin Copyright © 2012 Tri Yudani Mardining Raras et al. All rights reserved. An Early Morning Sputum Sample Is Necessary for the Diagnosis of Pulmonary Tuberculosis, Even with More Sensitive Techniques: A Prospective Cohort Study among Adolescent TB-Suspects in Uganda Tue, 04 Dec 2012 14:36:12 +0000 The World Health Organization (WHO) recommends collection of two sputum samples for tuberculosis (TB) diagnosis, with at least one being an early morning (EM) using smear microscopy. It remains unclear whether this is necessary even when sputum culture is employed. Here, we determined the diagnostic yield from spot and the incremental yield from the EM sputum sample cultures among TB-suspected adolescents from rural Uganda. Sputum samples (both spot and early-morning) from 1862 adolescents were cultured by the Lowenstein-Jensen (LJ) and Mycobacterium Growth Indicator Tube (MGIT) methods. For spot samples, the diagnostic yields for TB were 19.0% and 57.1% with LJ and MGIT, respectively, whereas the incremental yields (not totals) of the early-morning sample were 9.5% and 42.9% () with LJ and MGIT, respectively. Among TB-suspected adolescents in rural Uganda, the EM sputum culture has a high incremental diagnostic yield. Therefore, EM sputum in addition to spot sample culture is necessary for improved TB case detection. Willy Ssengooba, David P. Kateete, Anne Wajja, Eric Bugumirwa, Gerald Mboowa, Carolyn Namaganda, Germine Nakayita, Maria Nassolo, Francis Mumbowa, Benon B. Asiimwe, James Waako, Suzanne Verver, Philippa Musoke, Harriet Mayanja-Kizza, and Moses L. Joloba Copyright © 2012 Willy Ssengooba et al. All rights reserved.