http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Tue, 30 Apr 2013 10:43:41 +0000 http://www.hindawi.com/journals/trt/2013/312065/ 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. Mon, 15 Apr 2013 13:47:13 +0000 http://www.hindawi.com/journals/trt/2013/489865/ 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. Thu, 28 Mar 2013 15:24:20 +0000 http://www.hindawi.com/journals/trt/2013/108401/ 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. Sun, 24 Mar 2013 18:08:53 +0000 http://www.hindawi.com/journals/trt/2013/285094/ 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. Sun, 24 Mar 2013 13:18:42 +0000 http://www.hindawi.com/journals/trt/2013/670836/ 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. Thu, 28 Feb 2013 09:50:22 +0000 http://www.hindawi.com/journals/trt/2013/312824/ 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. Wed, 30 Jan 2013 11:31:07 +0000 http://www.hindawi.com/journals/trt/2013/535769/ 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. Mon, 14 Jan 2013 14:10:55 +0000 http://www.hindawi.com/journals/trt/2013/369717/ 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. Thu, 10 Jan 2013 16:16:12 +0000 http://www.hindawi.com/journals/trt/2013/549473/ 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. Sun, 23 Dec 2012 11:43:31 +0000 http://www.hindawi.com/journals/trt/2012/132406/ 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. Wed, 19 Dec 2012 08:55:13 +0000 http://www.hindawi.com/journals/trt/2012/230814/ 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. Tue, 18 Dec 2012 15:29:35 +0000 http://www.hindawi.com/journals/trt/2012/768603/ Soumitesh Chakravorty, Catharina Boehme, and Jongseok Lee Copyright © 2012 Soumitesh Chakravorty et al. All rights reserved. Thu, 13 Dec 2012 10:06:05 +0000 http://www.hindawi.com/journals/trt/2012/240132/ 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. Tue, 04 Dec 2012 14:36:12 +0000 http://www.hindawi.com/journals/trt/2012/970203/ 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. Sun, 25 Nov 2012 08:09:40 +0000 http://www.hindawi.com/journals/trt/2012/360852/ Background. Tuberculosis (TB) disease diagnosis in Vietnam relies on symptom screening, chest radiography (CXR), and acid fast bacilli (AFB) sputum smear which have a poor sensitivity in HIV patients. We evaluated the performance of clinical algorithms in screening and diagnosing AFB smear-negative TB in HIV patients. Methods. We enrolled 399 HIV-positive patients seeking care at a HIV clinic in Ho Chi Minh City (HCMC), Vietnam. Participants’ demographics, medical history, common TB symptoms, CXR, and laboratory tests were collected. Results. Of 399 HIV patients, 390 had initial AFB-negative smears and 22/390 patients had positive cultures. Symptom screening missed 54% (12/22) of smear-negative pulmonary TB (PTB) cases. Multivariate analysis found CD4+ cell level and CXR were significant PTB predictors. An algorithm combining four TB symptoms and TST presented a high sensitivity (100%), but poorly specific (24%) diagnostic performance for smear-negative PTB. Conclusion. Up to 54% of PTB cases in the HIV-infected population may be missed in the routine screening and diagnostic procedures used in Vietnam. Symptom screening was a poor overall diagnostic measure in detecting smear-negative TB in HIV patients. Our study results suggest that routine sputum cultures should be implemented to achieve a more accurate diagnosis of TB in HIV patients. Duc T. M. Nguyen, Hung Q. Nguyen, R. Palmer Beasley, Charles E. Ford, Lu-Yu Hwang, and Edward A. Graviss Copyright © 2012 Duc T. M. Nguyen et al. All rights reserved. Thu, 22 Nov 2012 17:09:17 +0000 http://www.hindawi.com/journals/trt/2012/892079/ Understanding the genetic diversity of Mycobacterium tuberculosis is needed for a better understanding of the epidemiology of TB and could have implications for the development of new diagnostics, drugs, and vaccines. M. tuberculosis isolates were characterized using spoligotyping and were compared with the SpoIDB4 database of the Pasteur Institute of Guadeloupe. A total of 53 different patterns were identified among 192 isolates examined. 169 of the isolates were classified into one of the 33 shared SITs, whereas the remaining 23 corresponded to 20 orphan patterns. 54% of the isolates were ascribed to the T family, a family which has not been well defined to date. Other prominent families were CAS, Haarlem, LAM, Beijing, and Unknown comprising 26%, 13%, 2.6%, 0.5%, and 2.1%, respectively. Among HIV-positive patients, 10 patterns were observed among 25 isolates. The T (38.5%), H (26.9%), and CAS (23.1%) families were the most common among HIV-positive individuals. The diversity of the M. tuberculosis strains found in this study is very high, and there was no difference in the distribution of families in HIV-positive and HIV-negative TB patients except the H family. Tuberculosis transmission in Addis Ababa is due to only the modern M. tuberculosis families (CAS, LAM, T, Beijing, Haarlem, and U). Adane Mihret, Yonas Bekele, Andre G. Loxton, Annemie M. Jordan, Lawrence Yamuah, Abraham Aseffa, Rawleigh Howe, and Gerhard Walzl Copyright © 2012 Adane Mihret et al. All rights reserved. Mon, 19 Nov 2012 17:15:53 +0000 http://www.hindawi.com/journals/trt/2012/747924/ Background. Tuberculosis (TB) patients registered in the government clinics under the DOTS (Directly Observed Treatment, Short Course) program in Chennai city catering to about 4.3 million population. Objective. To estimate the pattern and overall costs incurred by the new patients (who have never had treatment for tuberculosis or have taken antituberculosis drugs for less than one month) registered under DOTS program in the treatment of tuberculosis in Chennai city. Methodology. A cross-sectional survey among new TB patients, who had completed intensive phase of antituberculosis treatment, was done using a precoded semi-structured questionnaire between March and June 2007. Information was collected on demographic, socioeconomic characteristics and expenditure for before and during treatment. Mean costs were used for comparison. Results. Among the 300 TB patients, most economically productive age group and 186 (62%) were males. The overall estimated total costs incurred right from the onset of symptoms until treatment completion was found to be Rs. 3211 (3.8% of annual family income) under DOTS program, which is less compared to previous studies. The overall mean total cost was significantly high among male (Rs. 3270; ), employed (Rs. 3945; ), and extrapulmonary patients (Rs. 3915; ). Conclusion. The study has reiterated the fact that DOTS helps in reducing out-of-pocket expenses to patients with tuberculosis and hence is a cost-effective health intervention. This cost reduction may help to increase the access to the poor people which would help in achieving universal access to TB care services. Ramya Ananthakrishnan, M. Muniyandi, Anita Jeyaraj, Gopal Palani, and B. W. C. Sathiyasekaran Copyright © 2012 Ramya Ananthakrishnan et al. All rights reserved. Thu, 01 Nov 2012 15:32:59 +0000 http://www.hindawi.com/journals/trt/2012/791728/ Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host’s defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed. Wu Li, Guangcun Deng, Min Li, Xiaoming Liu, and Yujiong Wang Copyright © 2012 Wu Li et al. All rights reserved. Tue, 30 Oct 2012 09:20:46 +0000 http://www.hindawi.com/journals/trt/2012/218183/ Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterised serologically by cholestasis and the presence of high-titre antimitochondrial antibodies, and histologically by chronic nonsuppurative cholangitis and granulomata. As PBC is a granulomatous disease and Mycobacterium tuberculosis is the most frequent cause of granulomata, a causal relation between tuberculosis and PBC has been suggested. Attempts to find serological evidence of PBC-specific autoantibodies such as AMA have been made and, conversely, granulomatous livers from patients with PBC have been investigated for molecular evidence of Mycobacterium tuberculosis. This paper discusses in detail the reported data in support or against an association between Mycobacterium tuberculosis infection and PBC. We discuss the immunological and microbiological data exploring the association of PBC with exposure to Mycobacterium tuberculosis. We also discuss the findings of large epidemiologic studies investigating the association of PBC with preexistent or concomitant disorders and the relevance of these findings with tuberculosis. Genome-wide association studies in patients with tuberculosis as well as in patients with PBC provide conclusive hints regarding the assumed association between exposure to this mycobacterium and the induction of PBC. Analysis of these data suggest that Mycobacterium tuberculosis is an unlikely infectious trigger of PBC. Daniel S. Smyk, Dimitrios P. Bogdanos, Albert Pares, Christos Liaskos, Charalambos Billinis, Andrew K. Burroughs, and Eirini I. Rigopoulou Copyright © 2012 Daniel S. Smyk et al. All rights reserved. Tue, 02 Oct 2012 13:28:56 +0000 http://www.hindawi.com/journals/trt/2012/327027/ Background. Analysis of isoniazid (INH) uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2) genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liquid chromatography/mass spectrometry. Acetyl-INH/INH ratios were correlated with NAT-2 genotype. Results. Hair concentrations of INH, determined in 40 patients, were not dependent on ethnic group or body mass index and were significantly higher in male compared to female patients (median (range) 2.37 ng/mg (0.76–4.9) versus 1.11 ng/mg (0.02–7.20) (). Acetyl-INH/INH ratios were a median of 15.2% (14.5 to 31.7) in homozygous rapid acetylator NAT-2 genotype and 37.3% (1.73 to 51.2) in the heterozygous rapid acetylator NAT-2 genotype and both significantly higher than in the slow acetylator NAT-2 genotype with 5.8% (0.53 to 14.4) (). Conclusions. Results of hair analysis for INH showed lower concentrations in females. Acetyl-INH/INH ratios were significantly lower in patients with slow acetylator versus rapid acetylator genotypes. Michael Eisenhut, Detlef Thieme, Dagmar Schmid, Sybille Fieseler, and Hans Sachs Copyright © 2012 Michael Eisenhut et al. All rights reserved. Mon, 17 Sep 2012 10:25:34 +0000 http://www.hindawi.com/journals/trt/2012/170459/ A retrospective observational study was performed to determine the sensitivity and limitation of PCR test for the detection of Mycobacterium tuberculosis and M. avium complex. We obtained clinical specimens collected from the respiratory tract, cultured M. tuberculosis or M. avium complex, and performed PCR analysis. A total of 299 samples (M. tuberculosis, 177; M. avium, 35; M. intracellulare, 87) were analyzed by COBAS TaqMan PCR from April 2007 to March 2011. The PCR positivity rates were 50–55%, 70–100%, 88–98%, and 100% in smear-negative, smear 1+, 2+, and 3+ groups, respectively. The PCR positivity of tuberculosis in smear 1+ was 80.6%, which was statistically significantly () lower than that of smear 2+ (97.3%). From January 2005 to March 2007, we collected an additional 138 samples (M. tuberculosis, 74; M. avium, 21; M. intracellulare, 43), which were analyzed by COBAS Amplicor PCR. The PCR positivity rates obtained using COBAS TaqMan PCR and COBAS Amplicor PCR were not significantly different. The sensitivity of PCR test for mycobacteria is not sufficient in case of smear 1+. Careful consideration must be given to the interpretation of negative PCR test results in smear 1+, because smear-positive tuberculosis is the criterion for isolation. Satoshi Ikegame, Yoritake Sakoda, Nao Fujino, Kazuhito Taguchi, Masayuki Kawasaki, and Akira Kajiki Copyright © 2012 Satoshi Ikegame et al. All rights reserved. Sun, 26 Aug 2012 11:00:02 +0000 http://www.hindawi.com/journals/trt/2012/932862/ HIV-related tuberculosis is difficult to diagnose and is associated with high morbidity and mortality. Recently, the World Health Organization has endorsed the GeneXpert MTB/RIF (Xpert) assay for the diagnosis of pulmonary tuberculosis in HIV-infected patients from developing countries, but information about the use of Xpert for the diagnosis of extrapulmonary tuberculosis is scarce. In this study, we compared the performance of light-emitting diode (LED) auramine fluorescent microscopy and the Xpert assay for the diagnosis of tuberculosis in HIV infected patients in a district hospital of India. Although at higher cost, Xpert outperformed LED fluorescent microscopy in all type of specimens, especially in cerebrospinal fluid where the number of positive results was increased 11 times. Pleural fluid, ascitic fluid, pus, and stool specimens also yielded positive results with the Xpert assay. When collecting two additional early-morning sputum samples, the increase of the number of positive results with the Xpert assay was lower than previously reported for HIV infected patients. Rifampicin resistance was observed in 2.2% of the cases. The results of this study show that the Xpert assay can dramatically improve the rapid diagnosis of tuberculous meningitis and other types of extrapulmonary tuberculosis of HIV infected patients. Gerardo Alvarez-Uria, Jose M. Azcona, Manoranjan Midde, Praveen K. Naik, Srinivasulu Reddy, and Raghuprakash Reddy Copyright © 2012 Gerardo Alvarez-Uria et al. All rights reserved. Wed, 15 Aug 2012 11:34:00 +0000 http://www.hindawi.com/journals/trt/2012/834836/ Introduction. Multidrug resistance tuberculosis (MDR TB), the combined resistance of Mycobacterium tuberculosis to isoniazid (INH) and rifampin (RFM) is a major public health problem in India as it ranks second among the MDR-TB high burden countries worldwide. WHO recommends RFM resistance as a “surrogate marker” for detecting MDR. FNAC is the most widely used noninvasive investigative technique for TB lymphadenitis. Real-time polymerase chain reaction, an extremely versatile technique can be used for the timely detection and treatment of MDR TB by assessing RFM resistance status in the FNAC samples of TB lymphadenitis. Aim. To assess the status of rpoB gene by real-time PCR in FNAC samples of TB lymphadenitis. Materials and Methods. Thirty FNAC samples from patients with persistent LAP or appearance of new LAP after 5 months or more of Anti Tubercular Treatment were assessed for status of rpoB gene by Real-Time PCR using probe covering the “hot spot resistance” region of the rpoB gene. Result. By using probe covering codons 531 and 526 of rpoB gene, we could detect 17 of 30 (56.7%) rifampin resistant isolate. The PCR could detect Mtb DNA in 100% of cases. Conclusion. Use of molecular methods like Real-Time PCR for detection of MDR-TB in FNAC samples is time saving, logical and economical approach over the culture based method. Amita Raoot and Geeta Dev Copyright © 2012 Amita Raoot and Geeta Dev. All rights reserved. Mon, 30 Jul 2012 11:12:59 +0000 http://www.hindawi.com/journals/trt/2012/301056/ The information on the contribution of non tuberculous mycobacteria (NTM) to mycobacterial infections in Africa is scarce due to limited laboratory culture for its isolation and identification. One hundred and thirty-seven sputum smear positive patients were recruited into a study on the molecular epidemiology of Mycobacterium tuberculosis in Cross River State. Following sputum culture, 97 pure isolates were obtained and identified using Capilia TB-Neo and further confirmed by the GenoType Mycobacterium CM kit. Of the 97 isolates, 81 (83.5%) isolates were Capilia TB-Neo positive while 16 (16.5%) were Capilia TB-Neo negative. Further confirmation with the GenoType Mycobacterium CM kit revealed that 4 (25%) of the 16 isolates belonged to NTM and included M. fortuitum I, M. fortuitum II/M magaritense, M. abscessus, and M. avium ssp. The remaining 12 (75%) Capilia TB-Neo negative isolates were not members of the genus Mycobacterium despite their AFB appearance. Six (33.3%) of the Capilia TB-Neo negative were from HIV positive tuberculosis patients. All subjects in this study were placed on DOTS shortly after the AFB results were obtained. The implication of isolation of 16.5% nontuberculous isolates further emphasizes the need for culture of sputum specimen especially in HIV positive patients prior to administration of antituberculosis therapy. Benjamin Thumamo Pokam and Anne E. Asuquo Copyright © 2012 Benjamin Thumamo Pokam and Anne E. Asuquo. All rights reserved. Mon, 09 Jul 2012 08:18:14 +0000 http://www.hindawi.com/journals/trt/2012/716989/ Setting. Tanzania. Objective. To compare microscopy as conducted in direct observation of treatment, short course centers to pouched rats as detectors of Mycobacterium tuberculosis. Design. Ten pouched rats were trained to detect tuberculosis in sputum using operant conditioning techniques. The rats evaluated 910 samples previously evaluated by smear microscopy. All samples were also evaluated through culturing and multiplex polymerase chain reaction was performed on culture growths to classify the bacteria. Results. The patientwise sensitivity of microscopy was 58.0%, and the patient-wise specificity was 97.3%. Used as a group of 10 with a cutoff (defined as the number of rat indications to classify a sample as positive for Mycobacterium tuberculosis) of 1, the rats increased new case detection by 46.8% relative to microscopy alone. The average samplewise sensitivity of the individual rats was 68.4% (range 61.1–73.8%), and the mean specificity was 87.3% (range 84.7–90.3%). Conclusion. These results suggest that pouched rats are a valuable adjunct to, and may be a viable substitute for, sputum smear microscopy as a tuberculosis diagnostic in resource-poor countries. Amanda Mahoney, Bart J. Weetjens, Christophe Cox, Negussie Beyene, Klaus Reither, George Makingi, Maureen Jubitana, Rudovick Kazwala, Godfrey S. Mfinanga, Amos Kahwa, Amy Durgin, and Alan Poling Copyright © 2012 Amanda Mahoney et al. All rights reserved. Wed, 13 Jun 2012 11:32:01 +0000 http://www.hindawi.com/journals/trt/2012/827148/ Background. Delay in pulmonary tuberculosis (PTB) diagnosis is one of the major factors that affect outcome and threatens continued spread of tuberculosis. This study aimed at determining factors associated with delayed PTB diagnosis among human immunodeficiency virus (HIV) infected individuals. Methods. A retrospective observational study was done using clinic records of HIV-infected PTB suspects attending an HIV/AIDS clinic at Tintswalo rural hospital in South Africa (SA) between January 2006 and December 2007. Using routine clinic registers, 480 records were identified. Results. PTB diagnosis delay was found among 77/176 (43.8%) of the patients diagnosed with PTB. The mean delay of PTB diagnosis was 170.6 days; diagnosis delay ranged 1–30 days in 27 (35.1%) patients, 31–180 days in 24 (33.8%) patients; 24 (31.2%) patients remained undiagnosed for ≥180 days. Independent factors associated with delayed diagnosis were: older age >40 years (Odds Ratio (OR) 3.43, 95% CI 1.45–8.08) and virological failure (OR 2.72, 95% CI 1.09–6.74). Conclusion. There is a considerable delayed PTB diagnosis among HIV-infected patients in rural SA. Older patients as well as patients with high viral load are at a higher risk of PTB diagnosis delay. Therefore efforts to reduce PTB diagnosis delay need to emphasised. Respicious Boniface, Mosa Moshabela, Rose Zulliger, Peter MacPherson, and Peter Nyasulu Copyright © 2012 Respicious Boniface et al. All rights reserved. Wed, 30 May 2012 14:33:48 +0000 http://www.hindawi.com/journals/trt/2012/708423/ Objective. To analyse survival in patients with pulmonary tuberculosis (PTB) and factors associated with such survival. Design. Study of a cohort of patients aged over 14 years diagnosed with PTB from January 1, 1998 to July 31, 2005. During 2004–2006 a home visit was made to each patient and, during 2008-2009, they were visited again. During these visits a follow-up interview was administered; when the patient had died, a verbal autopsy was conducted with family members. Statistical analysis consisted of survival tests, Kaplan-Meier log-rank test and Cox regression. Results. Of 305 studied patients, 68 had died due to PTB by the time of the first evaluation, 237 were followed-up for a second evaluation, and 10 of them had died of PTB. According to the Cox regression, age (over 45 years) and treatment duration (under six months) were associated with a poorer survival. When treatment duration was excluded, the association between poorer survival with age persisted, whereas with having been treated via DOTS strategy, was barely significant. Conclusions. In the studied area it is necessary that patients receive a complete treatment scheme, and to give priority to patients aged over 45 years. J. C. Nájera-Ortiz, H. J. Sánchez-Pérez, H. Ochoa-Díaz-López, G. Leal-Fernández, and A. Navarro-Giné Copyright © 2012 J. C. Nájera-Ortiz et al. All rights reserved. Thu, 17 May 2012 11:51:39 +0000 http://www.hindawi.com/journals/trt/2012/481230/ Introduction. The Centers for Disease Control and Prevention (CDC)’s National Tuberculosis Surveillance System (NTSS) is the national repository of tuberculosis (TB) data in the United States. Jurisdictions report to NTSS through the Report of Verified Case of Tuberculosis (RVCT) form that transitioned to a web-based system in 2009. Materials and Methods. To improve RVCT data quality, CDC conducted a quality assurance (QA) needs assessment to develop QA strategies. These include QA components (case detection, data accuracy, completeness, timeliness, data security, and confidentiality); sample tools such as National TB Indicators Project (NTIP) to identify TB case reporting discrepancies; comprehensive training course; resource guide and toolkit. Results and Discussion. During July–September 2011, 73 staff from 34 (57%) of 60 reporting jurisdictions participated in QA training. Participants stated usefulness of sharing jurisdictions’ QA methods; 66 (93%) wrote that the QA tools will be effective for their activities. Several jurisdictions reported implementation of QA tools pertinent to their programs. Data showed >8% increase in NTSS and NTIP enrollment through Secure Access Management Services, which monitors system usage, from August 2011–February 2012. Conclusions. Despite challenges imposed by web-based surveillance systems, QA strategies can be developed with innovation and collaboration. These strategies can also be used by other disease programs to ensure high data quality. Lilia Ponce Manangan, Cheryl Tryon, Elvin Magee, and Roque Miramontes Copyright © 2012 Lilia Ponce Manangan et al. All rights reserved. Sun, 13 May 2012 10:07:21 +0000 http://www.hindawi.com/journals/trt/2012/831292/ Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis (TBM), is the severest form of Mycobacterium tuberculosis (M.Tb) infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available anti-tuberculosis treatment. The definitive diagnosis of CNS tuberculosis depends upon the detection of M.Tb bacilli in the cerebrospinal fluid (CSF). At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional “gold standard” based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect M.Tb in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional “gold standard”, the various molecular-based methods including nucleic acid amplification (NAA) assay technique, particularly polymerase chain reaction (PCR) assay, has emerged as a promising new method for the diagnosis of CNS tuberculosis because of its rapidity, sensitivity and specificity. In addition, the innovation of nested PCR assay technique is worthy of note given its contribution to improve the diagnosis of CNS tuberculosis. In this review, an overview of recent progress of the NAA methods, mainly highlighting the PCR assay technique, was presented. Teruyuki Takahashi, Masato Tamura, and Toshiaki Takasu Copyright © 2012 Teruyuki Takahashi et al. All rights reserved. Thu, 10 May 2012 08:10:17 +0000 http://www.hindawi.com/journals/trt/2012/931291/ Subpopulation structure of regulatory T cells and T helpers of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to antituberculosis drugs has been analyzed in this work. It has been shown that the leading part in immune suppression at infiltrative, dissemination, and fibrosis-cavity pulmonary tuberculosis is played by natural regulatory CD4+CD25+Foxp3+-T lymphocytes. Thus we estimate increase of their number in blood by drug-resistance and drug-susceptible patients. It has been demonstrated that in patients with fibrocavernous and infiltrative form of the disease and drug-resistant pulmonary tuberculosis the number of CD4+CD25−Foxp3+-regulatory T cells was increasing. In patients with infiltrative pulmonary tuberculosis, including multidrug-resistant M. tuberculosis, an increased number of CD3+CD4+CD25− T helpers is determined by the pathogenic features of the development of the tuberculosis infection and is connected with the activation of Th1-dependent immune response. Reduction in the number of T-helpers in the blood of patients with dissemination and fibrosis-cavity pulmonary tuberculosis mediates inefficient implementation of cell-mediated protective immunity. E. G. Churina, O. I. Urazova, and V. V. Novitskiy Copyright © 2012 E. G. Churina et al. All rights reserved.