Tuberculosis Research and Treatment The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Tuberculosis Case Finding in Benin, 2000–2014 and Beyond: A Retrospective Cohort and Time Series Study Mon, 16 May 2016 13:24:06 +0000 Objective. To determine any changes in tuberculosis epidemiology in the last 15 years in Benin, seasonal variations, and forecasted numbers of tuberculosis cases in the next five years. Materials and Methods. Retrospective cohort and time series study of all tuberculosis cases notified between 2000 and 2014. The “R” software version 3.2.1 (Institute for Statistics and Mathematics Vienna Austria) and the Box-Jenkins 1976 modeling approach were used for time series analysis. Results. Of 246943 presumptive cases, 54303 (22%) were diagnosed with tuberculosis. Annual notified case numbers increased, with the highest reported in 2011. New pulmonary bacteriologically confirmed tuberculosis (NPBCT) represented 78%  ± SD 2%. Retreatment cases decreased from 10% to 6% and new pulmonary clinically diagnosed cases increased from 2% to 8%. NPBCT notification rates decreased in males from 2012, in young people aged 15–34 years and in Borgou-Alibori region. There was a seasonal pattern in tuberculosis cases. Over 90% of NPBCT were HIV-tested with a stable HIV prevalence of 13%. The ARIMA best fit model predicted a decrease in tuberculosis cases finding in the next five years. Conclusion. Tuberculosis case notifications are predicted to decrease in the next five years if current passive case finding is used. Additional strategies are needed in the country. Serge Ade, Wilfried Békou, Mênonli Adjobimey, Omer Adjibode, Gabriel Ade, Anthony D. Harries, and Séverin Anagonou Copyright © 2016 Serge Ade et al. All rights reserved. Hematological and Biochemistry Profile and Risk Factors Associated with Pulmonary Tuberculosis Patients in Guyana Tue, 12 Apr 2016 12:51:42 +0000 Objective. To evaluate the hematological and biochemistry profile of patients with or without HIV-TB at the Georgetown Chest Clinic, Guyana. Methods. An observational, laboratory based study was designed to assess the relationship of PTB and HIV with patients routine biochemical and hematological values. The study was conducted during the period January 2013 to December 2014; a total sample size of 316 patients was enrolled following exclusion and inclusion criteria. Results. Mean age of study population was 40.1 ± 13.8 (95% CI 38.6–41.7) and most were between 40 and 49 age group (27.8%, 95% CI 23.2–33.0). More males were in the study 74.4% (95% CI 69.3–78.8) than females 81% (95% CI 21.1–30.7). 30% (95% CI 25.3–35.3) had a sputum smear grade of 3+ and 62.5% (95% CI 47.0–75.7) showed a CD4 count <200. The study demonstrated significantly low hemoglobin (Hb) 91.7% (95% CI 78.2–97.1), low WBC 27.8% (95% CI 15.8–44.0), high indirect bilirubin 7.4% (95% CI 2.1–23.3), ALT 41.8% (95% CI 28.4–56.7), and AST 72.2% (95% CI 57.3–83.3) among TB-HIV patients. Homelessness RR (relative risk) 2.2 (95% CI 0.48–12.3), smoking RR 1.09 (95% CI 1.01–1.19), and gender (male) RR 1.2 (95% CI 0.61–2.26) were main associated risk factors. Conclusions. There is slight variation among PTB and PTB-HIV coinfected patients in some hematological and biochemistry parameters. Rajini Kurup, Keon Flemming, Sudish Daniram, Shenika Marks-James, and Roberta Roberts Martin Copyright © 2016 Rajini Kurup et al. All rights reserved. Delay for First Consultation and Its Associated Factors among New Pulmonary Tuberculosis Patients of Central Nepal Sun, 10 Apr 2016 08:01:26 +0000 Tuberculosis (TB) is still a major public health challenge in Nepal and worldwide. Most transmissions occur between the onset of symptoms and the consultation with formal health care centers. This study aimed to determine the duration of delay for the first consultation and its associated factors with unacceptable delay among the new sputum pulmonary tuberculosis cases in the central development region of Nepal. An analytical cross-sectional study was conducted in the central development region of Nepal between January and May 2015. New pulmonary sputum positive tuberculosis patients were interviewed by using a structured questionnaire and their medical records were reviewed. Among a total of 374 patients, the magnitude of patient delay was 53.21% (95% CI: 48.12–58.28%) with a median delay of 32 days and an interquartile range of 11–70 days. The factors associated with unacceptable patient delay (duration ≥ 30 days) were residence in the rural area (adj. OR = 3.10, 95% CI: 1.10–8.72; value = 0.032) and DOTS center located more than 5 km away from their residences (adj. OR = 5.53, 95% CI: 2.18–13.99; value < 0.001). Unemployed patients were more likely to have patient delay (adj. OR = 7.79, 95% CI: 1.64–37.00; value = 0.010) when controlled for other variables. Wongsa Laohasiriwong, Roshan Kumar Mahato, Rajendra Koju, and Kriangsak Vaeteewootacharn Copyright © 2016 Wongsa Laohasiriwong et al. All rights reserved. Characteristics and Treatment Outcomes of Retreatment Tuberculosis Patients in Benin Thu, 24 Mar 2016 09:24:30 +0000 Objective. To determine among retreatment tuberculosis patients in Benin baseline characteristics, culture, and drug sensitivity testing (DST) results and treatment outcomes. Materials and Methods. A retrospective national cohort study of all retreatment tuberculosis patients in Benin in 2013 using registers and treatment cards. Results. Of 3957 patients with tuberculosis, 241 (6%) were retreatment cases. Compared to new pulmonary bacteriologically confirmed tuberculosis (NPBCT) patients, there were significantly higher numbers of males (), patients from “Atlantique-Littoral” (), patients aged 45–64 years (), and HIV-positive patients () among those retreated. Overall, 171 (71%) patients submitted sputum for DST, of whom (163) 95% were positive for Mycobacterium tuberculosis on Xpert MTB/RIF and/or culture and 17 (10%) were rifampicin resistant (9 with MDR-TB and 8 monoresistant to rifampicin). For those without MDR-TB (), treatment success was 93%. Worse outcomes occurred in those with unknown HIV status (RR: 0.27; 0.05–1.45; ) while better outcomes occurred in those who relapsed (RR: 1.06, 95 CI: 1.02–1.10, ). Conclusion. In 2013, a high proportion of retreatment patients received DST. Treatment success was good although more needs to be done to systematically increase the final follow-up smear examination. Reasons of high losses to follow-up from “Oueme-Plateau” should be investigated. Serge Ade, Omer Adjibodé, Prudence Wachinou, Narcisse Toundoh, Bérénice Awanou, Gildas Agodokpessi, Dissou Affolabi, Gabriel Adè, Anthony D. Harries, and Séverin Anagonou Copyright © 2016 Serge Ade et al. All rights reserved. Qualitative Assessment of Challenges in Tuberculosis Control in West Gojjam Zone, Northwest Ethiopia: Health Workers’ and Tuberculosis Control Program Coordinators’ Perspectives Tue, 15 Mar 2016 16:30:21 +0000 Background. Weak health systems pose many barriers to effective tuberculosis (TB) control. This study aimed at exploring health worker’s and TB control program coordinator’s perspectives on health systems challenges facing TB control in West Gojjam Zone, Amhara Region, Ethiopia. Methods. This was a qualitative descriptive study. Eight in-depth interviews with TB control program coordinators and two focus group discussions among 16 health workers were conducted. Purposive sampling was used to recruit study participants. Thematic analysis was used to identify and analyse main themes. Results. We found that intermittent interruptions of laboratory reagents and anti-TB drugs supplies, absence of trained and motivated health workers, poor TB data documentation, lack of adherence to TB treatment guideline, and lack of access to TB diagnostic tools at peripheral health institutions were challenges facing the TB control program performance in the study zone. Conclusions. Ensuring uninterrupted supply of anti-TB drugs and laboratory reagents to all health institutions is essential. Continuous refresher training of health workers on standard TB care and data handling and developing and implementing a sound retention strategy to attract and motivate health professionals to work in rural areas are necessary interventions to improve the TB control program performance in the study zone. Senedu B. Gebreegziabher, Solomon A. Yimer, and Gunnar A. Bjune Copyright © 2016 Senedu B. Gebreegziabher et al. All rights reserved. Health Seeking Behaviour and Associated Factors among Pulmonary Tuberculosis Suspects in Lay Armachiho District, Northwest Ethiopia: A Community-Based Study Sun, 28 Feb 2016 12:39:16 +0000 Studies in the northern part of Ethiopia showed high prevalence of undiagnosed cluster of tuberculosis cases within the community which demanded an investigation of the health care seeking behaviour of tuberculosis suspects. A community-based cross-sectional study was conducted in Lay Armachiho district, Northwest Ethiopia. Individuals who had cough for at least two weeks and aged greater than or equal to 15 years were included in the study. Data were collected by interview using pretested and structured questionnaire. Logistic regression was computed and adjusted odds ratio with 95% confidence interval was calculated. Out of the total population surveyed (29, 735), 663 (2.2%) individuals were found to be pulmonary tuberculosis suspects. Majority of the suspects reported that they had visited a modern health care facility. Those aged 15 to 34 and aged 35–54 had secondary educational level and above; those who were civil servants, those who were farmers, those who had previous history of tuberculosis treatment, and those who perceived that they were sick were more likely to visit a modern health care facility. The proportion of respondents who had taken traditional measures was found to be higher than some other districts. Improving the socioeconomic status of the community is recommended. Eshetu Haileselassie Engeda, Berihun Assefa Dachew, Hiwot Kassa Woreta, Mengistu Mekonnen Kelkay, and Tesfaye Demeke Ashenafie Copyright © 2016 Eshetu Haileselassie Engeda et al. All rights reserved. Socioeconomic Factors Associated with Knowledge on Tuberculosis among Adults in Ethiopia Mon, 01 Feb 2016 13:37:06 +0000 Background. Ethiopia is among highly tuberculosis affected countries. This might be related to low level of awareness on the disease in the population. The objective of the study was to determine the level of tuberculosis knowledge and socioeconomic factors associated with it. Methods. The 2011 Ethiopia health and demographic survey data were used. Overall tuberculosis knowledge score was computed to evaluate the outcome variable. Multivariable logistic regression was employed to identify independent socioeconomic factors associated with low tuberculosis knowledge. Results. The overall tuberculosis knowledge was low, 44.05% (95% CI: 42.05–46.24%) among women and 32.3% (95% CI: 30.34–34.32%) among men. Rural women (AOR = 1.22) and youth, no formal education (women: AOR = 3.28, men: AOR = 7.42), attending only primary education (women: AOR = 1.95, men: AOR = 3.49), lowest wealth quintiles (women: AOR = 1.4, Men: AOR = 1.28), unskilled female manual workers (AOR = 4.15), female agricultural employee (AOR = 2.28), and lack of access to media (women: AOR = 1.52, men: AOR = 1.71) are significantly associated with low tuberculosis knowledge. Conclusion. The level of tuberculosis knowledge among adults in Ethiopia is low and varied by socioeconomic groups. Tuberculosis control programs should consider appropriate strategies for tuberculosis education, promotion, communication, and social mobilization to address the rural women, youths, the poor, less educated people, and unskilled workers. Sifrash Meseret Gelaw Copyright © 2016 Sifrash Meseret Gelaw. All rights reserved. Endobronchial Tuberculosis Mimicking Asthma Sun, 20 Dec 2015 13:18:13 +0000 Endobronchial tuberculosis (EBTB) is defined as tuberculosis infection of the tracheobronchial tree with microbial and histopathological evidence. The clinical symptoms of the diseases are nonspecific. Chronic cough is the major symptom of the disease. The diagnosis is often delayed due to its nonspecific presentation and misdiagnosed as bronchial asthma. This case is presented to recall the notion that the endobronchial tuberculosis can mimic asthma and the importance of bronchoscopic evaluation in a patient with chronic cough and treatment resistant asthma. Serap Argun Baris, Tuğba Onyilmaz, Ilknur Basyigit, and Hasim Boyaci Copyright © 2015 Serap Argun Baris et al. All rights reserved. Performance of LED Fluorescence Microscopy for the Diagnosis of Pulmonary Tuberculosis in HIV Positive Individuals in Addis Ababa, Ethiopia Tue, 24 Nov 2015 12:23:40 +0000 Background. Despite its lower sensitivity, smear microscopy remains the main diagnostic method for pulmonary tuberculosis (PTB) in resource-limited countries as TB culturing methods like LJ (Lowenstein-Jensen) are expensive to use as a routine base. This study aimed to evaluate the performance of LED-FM for the diagnosis of PTB in HIV positive individuals. Methods. Cross-sectional study was conducted in Zewditu Memorial Hospital and Teklehaimanot Health Center HIV/ART clinics in Addis Ababa, Ethiopia. Each sample was stained with ZN and Auramine O staining and examined with bright-field microscope and LED-FM microscope, respectively. LJ culture was used as a reference. Results. Out of 178 study participants, twenty-four (13.5%) patients were confirmed as positive for MTB with LJ culture. The yield of ZN microscopy and LED-FM in direct and concentrated sample was 3.9%, 8.4%, 6.2%, and 8.4%, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of direct ZN microscopy were 29.2%, 100%, 100%, and 90.1%, respectively, and of LED-FM microscopy in direct sputum sample were 62.5%, 100%, 100%, and 94.5%, respectively. Conclusion. LED-FM has better sensitivity for the diagnosis of PTB in HIV positive individuals as compared to conventional ZN microscopy. LED-FM can be used as an alternative to conventional ZN microscopy. Konjit Getachew, Tamrat Abebe, Abebaw Kebede, Adane Mihret, and Getachew Melkamu Copyright © 2015 Konjit Getachew et al. All rights reserved. Association of Genetic Polymorphisms of IFNGR1 with the Risk of Pulmonary Tuberculosis in Zahedan, Southeast Iran Sun, 15 Nov 2015 08:21:41 +0000 Aim. The present study was undertaken to find out the possible association between interferon-gamma (IFN-γ) receptor 1 (IFNGR1) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Methods. Polymorphisms of IFNGR1 rs1327474 (−611 A/G), rs11914 (+189 T/G), rs7749390 (+95 C/T), and rs137854905 (27-bp ins/del) were determined in 173 PTB patients and 164 healthy subjects. Results. Our findings showed that rs11914 TG genotypes decreased the risk of PTB in comparison with TT (OR = 0.36, 95% CI = 0.21–0.62, and ). The rs11914 G allele decreased the risk of PTB compared with T allele (OR = 0.41, 95% CI = 0.25–0.68, and ). IFNGR1 rs7749390 CT genotype decreased the risk of PTB in comparison with CC genotype (OR = 0.55, 95% CI = 0.32–0.95, and ). No significant association was found between IFNGR1 rs1327474 A/G polymorphism and risk/protective of PTB. The rs137854905 (27-bp I/D) variant was not polymorphic in our population. Conclusion. Our findings showed that IFNGR1 rs11914 and rs7749390 variants decreased the risk of PTB susceptibility in our population. Mohammad Naderi, Mohammad Hashemi, Maryam Rezaei, and Abolhassan Safdari Copyright © 2015 Mohammad Naderi et al. All rights reserved. Evaluation of TB Case Finding through Systematic Contact Investigation, Chhattisgarh, India Mon, 06 Jul 2015 08:45:25 +0000 Rationale. Contact investigation is an established tool for early case detection of tuberculosis (TB). In India, contact investigation is not often conducted, despite national policy, and the yield of contact investigation is not well described. Objective. To determine the yield of evaluating household contacts of sputum smear-positive TB cases in Rajnandgaon district, Chhattisgarh, India. Methods. Among 14 public health care facilities with sputum smear microscopy services, home visits were conducted to identify household contacts of all registered sputum smear-positive TB cases. We used a standardized protocol to screen for clinical symptoms suggestive of active TB with additional referral for chest radiograph and sputa collection. Results. From December 2010 to May 2011, 1,556 household contacts of 312 sputum smear-positive TB cases were identified, of which 148 (9.5%) were symptomatic. Among these, 109 (73.6%) were evaluated by sputum examination resulting in 11 cases (10.1%) of sputum smear-positive TB and 4 cases (3.6%) of smear-negative TB. Household visits contributed additional 63% TB cases compared to passive case detection alone. Conclusion. A standard procedure for conducting household contact investigation identified additional TB cases in the community and offered an opportunity to initiate isoniazid chemoprophylaxis among children. Kshitij Khaparde, Pawan Jethani, Puneet K. Dewan, Sreenivas A. Nair, Madhav Rao Deshpande, Srinath Satyanarayana, Shamim Mannan, and Patrick K. Moonan Copyright © 2015 Kshitij Khaparde et al. All rights reserved. Prevalence of Tuberculosis, Drug Susceptibility Testing, and Genotyping of Mycobacterial Isolates from Pulmonary Tuberculosis Patients in Dessie, Ethiopia Tue, 09 Jun 2015 16:10:50 +0000 Due to their initially seemingly high cost, timely diagnosis and effective treatment of tuberculosis (TB) are usually hampered by lack or shortage of resources in many high TB burden countries. However, the benefits of effective treatment can eventually outweigh those of empirical treatment. Here, a cross-sectional study was conducted on samples from smear-positive new and retreatment TB patients. Data on sociodemographic and HIV status were collected. Samples were cultured for identification, conventional drug sensitivity testing, and molecular typing by deletion typing and spoligotyping. The results showed the youth were disproportionately affected. New cases were being treated following general treatment guidelines only. Monoresistance or multiple drug resistance was found in 16.5% of new patients. Spoligotyping showed that there were 44 patterns with families H3 and T1 (lineage 4) and CAS-Delhi (lineage 3) being dominant. Some rare patterns from lineage 7 were also found. Spoligotype pattern, HIV positivity, and previous treatment were not associated with drug resistance. That the vast majority of the patients were new cases and young and the large number of these patients with mono- or multiple drug resistance indicate that most TB cases are due to recent transmissions and that urgent actions are needed to curb the transmissions. Minwuyelet Maru, Solomon H. Mariam, Tekle Airgecho, Endalamaw Gadissa, and Abraham Aseffa Copyright © 2015 Minwuyelet Maru et al. All rights reserved. Comparison of Xpert MTB/RIF Assay and the Conventional Sputum Microscopy in Detecting Mycobacterium tuberculosis in Northern Thailand Thu, 30 Apr 2015 17:23:14 +0000 Background. Despite low sensitivity in detection of Mycobacterium tuberculosis, sputum acid-fast smear remains the main diagnostic method. This study aimed to compare the diagnostic performance of Xpert MTBRIF assay versus conventional sputum acid-fast smear. Materials and Methods. A cross-sectional study was conducted at Chiang Mai University Hospital, Thailand. Patients who were ≥15 years old and had clinically suspected pulmonary tuberculosis were included. Results. 109 specimens from 57 patients were included. Using MGIT sputum culture as a reference standard, the sensitivity (SEN) and specificity (SPEC) for Xpert were 95.3% (95% CI, 84.2%, 99.4%) and 86.4% (95% CI, 75.7%, 93.6%). The SEN and SPEC for sputum acid-fast smear were 60.5% (95% CI, 44.4%, 75.0%) and 98.5% (95% CI, 91.8%, 100%). Xpert had significantly higher sensitivity ( value < 0.001) and lower specificity ( value = 0.022) than sputum acid-fast smear. Among 43 culture-proven M. tuberculosis specimens, sensitivity of Xpert was 100% (95% CI, 86.7%, 100%) in acid-fast positive smears () and 88.2% (95% CI, 63.5%, 98.5%) in acid-fast negative smears (). Conclusions. The good sensitivity and specificity of Xpert assay in detecting M. tuberculosis from sputum specimens may help in early diagnosis and treatment of pulmonary tuberculosis, particularly among patients who had acid-fast negative sputum smear. Kanokwan Pinyopornpanish, Romanee Chaiwarith, Chansom Pantip, Rassamee Keawvichit, Kanlaya Wongworapat, Phadungkiat Khamnoi, Khuanchai Supparatpinyo, and Thira Sirisanthana Copyright © 2015 Kanokwan Pinyopornpanish et al. All rights reserved. Multiplex Analysis of Pro- or Anti-Inflammatory Serum Cytokines and Chemokines in relation to Gender and Age among Tanzanian Tuberculous Lymphadenitis Patients Tue, 28 Apr 2015 12:22:06 +0000 Objectives. Tuberculous lymphadenitis is the most common form of extrapulmonary tuberculosis (TB) with a female and paediatric preponderance, postulated to be due to differences in the immune response. The aim of this study was to analyze the differences in the serum cytokine levels of tuberculous lymphadenitis patients with respect to age and gender. Methods. A multiplex bead-based enzyme-linked immunosorbent assay was used to measure IFN-γ, TNF-α, GM-CSF, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, and IL-17 levels in sera of patients and healthy controls . Results. Levels of IFN-γ, TNF-α, GM-CSF, IL-1β, IL-2, IL-4, and IL-6 were higher in adult patients than in controls, while those of IL-12 were lower . Children had lower levels of TNF-α, GM-CSF, and IL-5 and higher levels of IL-2 compared with adult patients . The male adult patients had higher levels of IL-17 and lower levels of IL-12 compared with female adult patients .  Conclusion. There were significant differences in the levels of circulating cytokines with respect to gender and age. Children had generally lower levels of cytokines as compared to adults, which could make them more susceptible. Findings do not support that female preponderance is due to differences in immune response. Tehmina Mustafa, Karl Albert Brokstad, Sayoki G. Mfinanga, and Harald G. Wiker Copyright © 2015 Tehmina Mustafa et al. All rights reserved. The Application of GeneXpert MTB/RIF for Smear-Negative TB Diagnosis as a Fee-Paying Service at a South Asian General Hospital Wed, 08 Apr 2015 13:12:52 +0000 The GeneXpert MTB/RIF assay (Xpert) is a novel automated diagnostic tool for tuberculosis but its optimal placement in the healthcare system has not been determined. The objective of this study was to determine the possibility of additional case detection for pulmonary tuberculosis (PTB) by offering Xpert to smear-negative patients in a low-HIV burden setting with no Mycobacterium tuberculosis (M.tb.) culture facilities. Patients routinely presenting with symptoms suggestive of PTB with negative smears were offered single Xpert test on a fee-paying basis. Data were retrospectively reviewed to determine case detection in patients tested from February to December 2013. Symptoms associated with a positive test were analysed to determine if refinement of clinical criteria would reduce unnecessary testing. 258 smear-negative patients were included and M.tb. was detected in 55 (21.32%, ). Using standard clinical assessment for selection, testing 5 patients detected one case of smear-negative PTB. These results demonstrate that fee-paying Xpert service in low-income setting can increase TB case confirmation substantially and further systematic studies of health economic implications should be conducted to determine optimal implementation models to increase access to Xpert in low- and middle-income countries. Poojan Shrestha, Amit Arjyal, Maxine Caws, Krishna Govinda Prajapati, Abhilasha Karkey, Sabina Dongol, Saruna Pathak, Shanti Prajapati, and Buddha Basnyat Copyright © 2015 Poojan Shrestha et al. All rights reserved. Determinants of Pulmonary Tuberculosis among Inmates at Mangaung Maximum Correctional Facility in Bloemfontein, South Africa Tue, 17 Mar 2015 09:38:49 +0000 Introduction. Correctional facilities house large number of inmates who are at high risk of developing tuberculosis (TB); however factors associated with TB among inmates at Mangaung Correctional Centre have not been studied. Study Population and Methods. We undertook a case control study and reviewed a total of 1140 medical records of inmates treated for TB between 2009 and 2010. Cases were selected randomly from the medical records of inmates who were treated. Data collected were analysed using STATA version 12.0 and determinants of TB were evaluated using multiple logistic regression analyses. Factors with were considered significant. Results. Prevalence of TB was 8.8% and 52% of inmates with TB were aged 31–40 years; 58% of the TB cases were HIV positive and 34% of them had CD4 cell count 350 cells/mm3. Factors associated with TB among inmates were HIV coinfection (OR: 4.2; 95% CI: 2.64–7.00); previous history of TB disease (OR: 3.58; 95% CI: 2.25–5.70); and smoking (OR: 2.1; 95% CI: 1.16–3.81). Conclusion. Interventions to improve TB detection such as regular screening of inmates with such factors need to be reinforced to control transmission of TB among inmates and the community. Peter Nyasulu, Serame Mogoere, Teye Umanah, and Geoffrey Setswe Copyright © 2015 Peter Nyasulu et al. All rights reserved. Evaluation of a U.S. Public Health Laboratory Service for the Molecular Detection of Drug Resistant Tuberculosis Sun, 22 Feb 2015 09:16:29 +0000 Crucial to interrupting the spread of tuberculosis (TB) is prompt implementation of effective treatment regimens. We evaluated satisfaction, comfort with interpretation, and use of molecular results from a public health service provided by the Centers for Disease Control and Prevention (CDC) for the molecular detection of drug resistant Mycobacterium tuberculosis complex (MTBC). An electronic survey instrument was used to collect information anonymously from U.S. Public Health Laboratories (PHL) that submitted at least one isolate of MTBC to CDC from September 2009 through February 2011. Over 97% of those responding expressed satisfaction with the turnaround time for receiving results. Twenty-six PHL (74%) reported molecular results to healthcare providers in less than two business days. When comparing the molecular results from CDC with their own phenotypic drug susceptibility testing, 50% of PHL observed discordance. No respondents found the molecular results difficult to interpret and 82% were comfortably discussing them with TB program officials and healthcare providers. Survey results indicate PHL were satisfied with CDC’s ability to rapidly provide interpretable molecular results for isolates of MTBC submitted for determination of drug resistance. To develop educational materials and strategies for service improvement, reasons for discordant results and areas of confusion need to be identified. Mitchell A. Yakrus, Beverly Metchock, and Angela M. Starks Copyright © 2015 Mitchell A. Yakrus et al. All rights reserved. Arginine Adjunctive Therapy in Active Tuberculosis Tue, 03 Feb 2015 14:01:21 +0000 Background. Dietary supplementation has been used as a mechanism to augment the immune system. Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis. Methods. In a randomized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. The final treatment success, sputum conversion, weight gain, and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR, CRP, and Hg. Data were collected and analyzed with SPSS software (ver. 18). Results. Arginine supplementation reduced constitutional symptoms () in patients with smear-positive TB at the end of the first month of treatment. Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment ( and ) and a reduced CRP at the end of the first month of treatment () versus placebo group. Conclusion. Arginine is useful as an adjunctive therapy in patients with active tuberculosis, in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain. This trial is registered with Clinical Trials Registry of Iran: IRCT201211179855N2. Aliasghar Farazi, Omid Shafaat, Masoomeh Sofian, and Manijeh Kahbazi Copyright © 2015 Aliasghar Farazi et al. All rights reserved. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker? Wed, 28 Jan 2015 08:44:10 +0000 BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine. Sarman Singh, Manoj Kumar, and Pragati Singh Copyright © 2015 Sarman Singh et al. All rights reserved. Five-Year Assessment of Time of Sputum Smears Conversion and Outcome and Risk Factors of Tuberculosis Patients in Central Iran Wed, 14 Jan 2015 09:31:10 +0000 Objective. To evaluate risk factors which influence sputum smear conversion, outcome, and trends of conversion of sputum smear during 5 years and compare outcomes in patients with different regimens. Methods. In a retrospective cohort study, all patients with sputum smear positive tuberculosis were evaluated for comorbidities and demographic, microbiological, and therapeutic data and outcome. Smear examinations were performed at the beginning, at 2 months for CAT I, at 3 months for CAT II, at the end of second month of maintenance phase, and at the end of treatment. Results. This study enrolled 211 sputum smear positive patients, but 189 patients who completed the intensive phase of treatment were evaluated. Sputum smear of 158 patients converted at the end of intensive phase (83.6). Univariate analysis indicated that the risk of a persistent positive smear at the end of intensive phase was greater in diabetic patients ((odds 4.038, 95% CI 1.123–14.516) ), and also a 3+bacillary load had risk of 2.933-fold ((95% CI 1.278–6.732) ). Overall rate of unfavorable outcome was 20.9%. Factors associated with unfavorable outcome were age (P value 0.000), male gender (P value 0.027), diabetes (P value 0.000), and delayed conversion of sputum at the end of intensive phase (P value 0.000). Outcome for different regimens was not different significantly. Two specimens were isoniazid resistant. Conclusions. We suggest supervised treatment and care for diabetic patients and those with higher bacillary load. Paying attention to early diagnosis of tuberculosis in the elderly to reduce poor outcome and further measures to prevent transfer-out could improve the success rate. Fatemah Behnaz, Mahmoud Mohammadzadeh, and Golnaz Mohammadzade Copyright © 2015 Fatemah Behnaz et al. All rights reserved. Mefloquine and Its Enantiomers Are Active against Mycobacterium tuberculosis In Vitro and in Macrophages Thu, 11 Dec 2014 08:54:12 +0000 Objective. Tuberculosis is a serious problem of public health. The increase on the number of clinical cases of tuberculosis infected with multidrug resistant (MDR) M. tuberculosis calls for the development of novel therapy. Design. We investigated the effect of mefloquine and two enantiomers, (+)erythro-mefloquine and (+)threo-mefloquine against M. tuberculosis strains in the environment resembling the aspects of the granuloma environment and in macrophages. Results. The results suggest that mefloquine (racemic mixture) and (+)erythro-mefloquine have bactericidal activity against M. tuberculosis strains both in acidic, low oxygen tension and in macrophages. The activity, however, was impaired under increased osmolarity. Conclusion. Identification of the target for mefloquine in the pathogen will allow for the development of novel drugs with antituberculosis activity. Luiz E. Bermudez and Laura Meek Copyright © 2014 Luiz E. Bermudez and Laura Meek. All rights reserved. Adverse Reactions to Antituberculosis Drugs in Iranian Tuberculosis Patients Mon, 24 Nov 2014 12:48:51 +0000 Background. Antituberculosis multidrug regimens have been associated with increased incidence of adverse drug reactions (ADRs). This study aimed to determine the incidence and associated factors of ADRs due to antituberculosis therapy. Methods. This is a retrospective cross-sectional study on tuberculosis patients who were treated in tuberculosis clinics in Markazi province in Iran. The information contained in the medical files was extracted and entered into the questionnaire. Data was descriptively analyzed by using statistical package for social sciences (SPSS 18). Results. A total of 940 TB patients of 1240 patients’ medical records available in 10 medical offices were included in this study. Of the 563 ADRs found in this study, 82.4% were considered minor reactions and 17.6% were major reactions. No death from antituberculosis ADR was observed. We found that the risk of major ADRs was higher in females (), age >50 y (), coinfection with HIV (), smoking (), retreatment TB (), and comorbidities (). Conclusions. This study showed that severe side effects of anti-TB drugs are common in patients who have risk factors of ADRs and they should be followed up by close monitoring. Aliasghar Farazi, Masoomeh Sofian, Mansoureh Jabbariasl, and Sara Keshavarz Copyright © 2014 Aliasghar Farazi et al. All rights reserved. Extensive Genetic Diversity among Clinical Isolates of Mycobacterium tuberculosis in Central Province of Iran Wed, 19 Nov 2014 08:05:28 +0000 Human tuberculosis caused by Mycobacterium tuberculosis (Mtb) remains a significant disease in many countries. According to Iran’s borders with Afghanistan and Pakistan, which are among the 22 high burden countries around the world, this study was conducted to analyze the current molecular epidemiology of tuberculosis and survey genetic diversity of Mtb strains in Markazi Province in center of Iran. In this experimental study, 75 sputum specimens and one gastric lavage from all smear-positive TB patients admitted to the public hospitals across the Markazi Province were cultured on specific mycobacterial culture media. Genomic DNA was digested by PvuII and transferred to positively charged nylon membrane by southern blotting method and hybridization by PGRS and DR probes. Genotyping of the isolates by PGRS-RFLP and DR-RFLP displayed a wide range of genetic diversity as 25 and 26 genotypes were identified, respectively. Generally speaking, despite the relatively limited number of isolates in the study, high age of patients and also large heterogeneity found in the setting are both in opposition to active circulation of Mtb strains between patients under study either Iranian or Afghan nationals. Thus, it seems that reactivation of latent infection has had the main role in the spread of tuberculosis. Saman Soleimanpour, Daryoush Hamedi Asl, Keyvan Tadayon, Ali Asghar Farazi, Rouhollah Keshavarz, Kioomars Soleymani, Fereshteh Sadat Seddighinia, and Nader Mosavari Copyright © 2014 Saman Soleimanpour et al. All rights reserved. Profile, Outcomes, and Determinants of Unsuccessful Tuberculosis Treatment Outcomes among HIV-Infected Tuberculosis Patients in a Nigerian State Sun, 16 Nov 2014 07:52:01 +0000 Background. Few studies have evaluated the rate of tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection and the determinants of its treatment outcomes in Africa. We aimed to determine the predictors of unsuccessful treatment outcomes in HIV-infected tuberculosis patients in Nigeria. Methods. A retrospective cohort study design was used to assess adult TB/HIV patients who registered for TB treatment in two health facilities in Ebonyi State, Southeast Nigeria, between January 2011 and December 2012. Predictors of unsuccessful treatment outcomes were determined using multivariable logistic regression analysis. Results. Of 1668 TB patients, 342 (20.5%) were HIV coinfected. Of these, 195 (57%) had smear-negative pulmonary TB and 11 (3.2%) had extrapulmonary TB. Overall, 225 (65.8%) patients achieved successful outcomes, while 117 (34.2%) had unsuccessful outcomes. The unsuccessful treatment outcomes were due to “default” (9.9%), “death” (19%), “treatment failure” (1.5%), and “transferring out” (3.8%). Independent determinants for unsuccessful outcomes were receiving care at a public facility and noninitiation of antiretroviral therapy. Conclusion. There is need for the reevaluation of the quality of public sector treatment services provided for TB/HIV patients as well as further expansion of TB/HIV collaborative activities in rural areas, and interventions to reduce mortality and default rates among TB/HIV patients are urgently needed in Nigeria. Daniel Chukwunweolu Oshi, Sarah Nakalema Oshi, Isaac Alobu, and Kingsley Nnanna Ukwaja Copyright © 2014 Daniel Chukwunweolu Oshi et al. All rights reserved. Photovoice: A Novel Approach to Improving Antituberculosis Treatment Adherence in Pune, India Tue, 07 Oct 2014 09:21:09 +0000 We compared antituberculosis treatment (ATT) adherence and outcomes among patients exposed to Photovoice (video of previously cured TB patients sharing experiences about TB treatment) versus those not exposed. The odds of successful outcome (i.e., cured or completing treatment) for the 135 patients who watched Photovoice were 3 times greater (odds ratio: 2.8; 95% CI: 1.3–6.1) than for patients who did not watch Photovoice. The comparison group, on average, missed more doses (10.9 doses; 95% CI: 6.6–11.1) than the intervention group who saw Photovoice (5.5 doses; 95% CI: 3.7–6.1). Using Photovoice at initiation of ATT has the potential to improve treatment adherence and outcomes. Sangita C. Shelke, Prakash S. Adhav, Patrick K. Moonan, Matthew Willis, Malan A. Parande, Srinath Satyanarayana, Vikas D. Kshirsagar, and Smita Ghosh Copyright © 2014 Sangita C. Shelke et al. All rights reserved. Treatment Outcome of Tuberculosis Patients Registered at DOTS Centre in Ogbomoso, Southwestern Nigeria: A 4-Year Retrospective Study Sun, 28 Sep 2014 14:01:58 +0000 Background Information. Monitoring outcome of tuberculosis treatment and understanding the specific reasons for unsuccessful treatment outcome are important in evaluating the effectiveness of tuberculosis control program. This study investigated tuberculosis treatment outcomes and predictors for unsuccessful treatment outcome in Ogbomoso town, Southwestern Nigeria. Methodology. Medical records of all tuberculosis patients registered from January 2008 to December 2011 in 5 Local Government areas, Ogbomoso, Southwestern Nigeria, were reviewed. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control guideline. Bivariate analysis was used to analyse the association between treatment outcome and potential predictor variables. Results. Out of the 965 total TB patients (579 males and 386 females) with mean age 42.4 ± 1.9 years, 866 (89.74%) were categorized as pulmonary tuberculosis and 109 (11.30%) as extrapulmonary tuberculosis. Treatment outcome among total 914 subjects was as follows: 304 (33.26%) patients got cured, 477 (52.19%) completed treatment, 87 (9.52%) died, 9 (0.98%) defaulted, and 1 (0.11%) failed treatment while 36 (3.94%) were transferred out. Higher treatment success rate was associated with those on Category 1 treatment (). Conclusion. The treatment success rate of tuberculosis patients was high (85.45%) compared to national target. However, certain proportion of patients died (9.52%) and defaulted (0.98%), which is a serious public health concern that needs to be addressed urgently. Olarewaju Sunday, Olanrewaju Oladimeji, Folorunso Ebenezer, Babatunde Akintunde, Temitayo-Oboh Abiola, Abdulsalam Saliu, and Oluwatoyin Abiodun Copyright © 2014 Olarewaju Sunday et al. All rights reserved. Listening to Those at the Frontline: Patient and Healthcare Personnel Perspectives on Tuberculosis Treatment Barriers and Facilitators in High TB Burden Regions of Argentina Sun, 28 Sep 2014 09:53:26 +0000 Purpose. In Argentina, tuberculosis (TB) control measures have not achieved key treatment targets. The purpose of this study was to identify modes of treatment delivery and explore patient and healthcare personnel perceptions of barriers and facilitators to treatment success. Methods. We used semistructured group and individual interviews for this descriptive qualitative study. Eight high burden municipalities were purposively selected. Patients in treatment for active TB , multidisciplinary TB team members , and TB program directors at local, municipal, regional, and national levels were interviewed. Interviews were recorded, transcribed verbatim, and analyzed using thematic analysis. Results. Modes of treatment delivery varied across municipalities and types of healthcare facility and were highly negotiated with patients. Self-administration of treatment was common in hospital-based and some community clinics. Barriers to TB treatment success were concentrated at the system level. This level relied heavily on individual personal commitment, and many system facilitators were operating in isolation or in limited settings. Conclusions. We outline experiences and perspectives of the facilitating and challenging factors at the individual, structural, social, and organizational levels. Establishing strong patient-healthcare personnel relationships, responding to patient needs, capitalizing on community resources, and maximizing established decentralized system could mitigate some of the barriers. Sarah J. Iribarren, Fernando Rubinstein, Vilda Discacciati, and Patricia F. Pearce Copyright © 2014 Sarah J. Iribarren et al. All rights reserved. In Silico Antitubercular Activity Analysis of Benzofuran and Naphthofuran Derivatives Thu, 11 Sep 2014 09:21:55 +0000 For the human health, Mycobacterium tuberculosis (MTB) is the deadliest enemy since decades due to its multidrug resistant strains. During latent stage of tuberculosis infection, MTB consumes nitrate as the alternate mechanism of respiration in the absence of oxygen, thus increasing its survival and virulence. NarL is a nitrate/nitrite response transcriptional regulatory protein of two-component signal transduction system which regulates nitrate reductase and formate dehydrogenase for MTB adaptation to anaerobic condition. Phosphorylation by sensor kinase (NarX) is the primary mechanism behind the activation of NarL although many response regulators get activated by small molecule phospho-donors in the absence of sensor kinase. Using in silico approach, the molecular docking of benzofuran and naphthofuran derivatives and dynamic study of benzofuran derivative were performed. It was observed that compound Ethyl 5-bromo-3-ethoxycarbonylamino-1-benzofuran-2-carboxylate could be stabilized at the active site for over 10 ns of simulation. Here we suggest that derivatives of benzofuran moiety can lead to developing novel antituberculosis drugs. Prashantha Karunakar, Chamarahalli Ramakrishnaiyer Girija, Venkatappa Krishnamurthy, Venkatarangaiah Krishna, and Kunigal Venugopal Shivakumar Copyright © 2014 Prashantha Karunakar et al. All rights reserved. The Quality of Tuberculosis Services in Health Care Centres in a Rural District in Uganda: The Providers’ and Clients’ Perspective Sun, 07 Sep 2014 09:21:56 +0000 Quality of care plays an important role in the status of tuberculosis (TB) control, by influencing timely diagnosis, treatment adherence, and treatment completion. In this study, we aimed at establishing the quality of TB service care in Kamuli district health care centres using Donabedian structure, process, and outcomes model of health care. A cross-sectional study was conducted in 8 health care facilities, among 20 health care workers and 392 patients. Data was obtained using face-to-face interviews, an observation guide, a check list, and record review of the TB unit and laboratory registers. Data entry and analysis were done using EPI INFO 2008 and STATA 10 versions, respectively. A high number 150 (87.21%) of TB patients were not aware of all the signs to stop TB medication, and 100 (25.51%) patients received laboratory results after a period of 3–5 working days. The major challenges faced by health workers were poor attitude of fellow health workers, patients defaulting treatment, and fear of being infected with TB. One of the worst performance indicators was low percentage of cure. Comprehensive strengthening of the health system focusing on quality of support supervisions, patient follow up, promoting infection control measures, and increasing health staffing levels at health facilities is crucial. Lilian Bulage, Juliet Sekandi, Omar Kigenyi, and Ezekiel Mupere Copyright © 2014 Lilian Bulage et al. All rights reserved. Source Case Investigation for Children with TB Disease in Pune, India Wed, 27 Aug 2014 08:09:20 +0000 Setting. Contact tracing is broadly encouraged for tuberculosis (TB) control. In many high-burden countries, however, little effort is made to identify contacts of newly diagnosed TB patients. This failure puts children, many of whom live in poor crowded communities, at special risk. Objectives. To perform source-case investigations for 50 pediatric TB cases in Pune, India. Design. A descriptive cross-sectional observational study of pediatric TB cases < 5 years of age. Information was collected about the index case and household contacts. Results. In 15 (30%) of the 50 pediatric index cases, the household contained known TB contacts, 14 (86%) of whom were adults. Prior to their own diagnosis of TB, only one of the 15 pediatric index cases who met criteria for isoniazid preventive therapy received it. The index cases with known household TB contacts had a longer delay in initiating TB treatment than those without TB contacts (17.5 versus 2 days; ). Use of contact tracing identified 14 additional household TB suspects, 8 (57%) of whom were children. Conclusions. This study identified missed opportunities for TB prevention, as contact tracing is poorly implemented in resource-limited countries, like India. Further strategies to improve the implementation of TB prevention, especially in young children, are urgently needed. Debalina De, Aarti Kinikar, P. S. Adhav, Sunanda Kamble, Prasanna Sahoo, Hari Koli, Savita Kanade, Vidya Mave, Nishi Suryavanshi, Nikhil Gupte, Amita Gupta, and Jyoti Mathad Copyright © 2014 Debalina De et al. All rights reserved.