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Ablo Prudence Wachinou, , , Berenice Awanou, , Wilfried Bekou, Marius Esse, Gabriel Ade, ,
Journal of Tuberculosis Research, Volume 05, pp 189-200;

Background: In Benin, little is known about the influence of both gender and HIV-status on diagnostic patterns and treatment outcomes of Tuber-culosis (TB) patients. Objective: To assess whether differences in gender and HIV status affect diagnostic patterns and treatment outcomes of TB patients. Methods: Retrospective cohort study of patients registered in 2013 and 2014 in the three largest TB Basic Management Units in south Benin. Results: Of 2694 registered TB patients, 1700 (63.1%) were male. Case notification rates were higher in males compared with females (96 vs 53/100,000 inhabitants). The male to female ratio was 1:1 in HIV positive patients, but was 2:1 among HIV negative cases. In HIV-positive patients, there were no differences in TB types between men and women. In HIV-negative patients, there were significantly higher proportions of females with clinically diagnosed pulmonary TB (p = 0.04) and extrapulmonary TB (p < 0.001). Retreatment TB was 4.65 times higher amongst males compared with females. For New bacteriologically confirmed pulmonary TB, no differences were observed in treatment outcomes between genders in the HIV positive group; but significantly more unfavorable outcomes were reported among HIV negative males, with higher rates of failure (p < 0.001) and loss-to-follow up (p = 0.02). Conclusion: The study has shown that overall TB notification rates were higher in males than in females in south Benin, with more females co-infected with HIV. Unfavorable outcomes were more common in HIV-negative males.
Risara Jaksuwan, Prasit Tharavichikul, Charoen Chuchottaworn, Jayanton Patumanond, Piyada Kunawararak, Jongkolnee Settakorn
Journal of Tuberculosis Research, Volume 05, pp 178-188;

Background: Extensively drug resistant tuberculosis (XDR-TB) is a serious problem in public health and XDR-TB patients usually develop from multi-drug resistance tuberculosis (MDR-TB) and pre-XDR-TB. The rapid molecular test for drug susceptibility testing (DST) can be used for early detection to prevent XDR-TB. Methods: We examined 34 clinical Mycobacterium tuberculosis (M. tuberculosis) isolates from MDR/XDR-TB patients in the upper north of Thailand that were identified with drug susceptibility profiles by indirect agar proportion method from 2005-2012. Our study investigated the genetic mutations in gyrA for ofloxacin resistance and rrs for kanamycin resistance. The genetic mutations and drug susceptibility test results were analyzed using the exact test. Results: The majority of the ofloxacin resistance was detected in gyrA 21, gyrA 70, gyrA 87, gyrA 102, gyrA 162, and gyrA 187 were at 0%, 12.5%, 37.5%, 0%, 50.0% and 25.0% sensitivity, respectively, and at 96.2, 96.2%, 20.1%, 96.2%, 57.7% and 61.5% specificity, respectively. Kanamycin resistance was found in rrs 512, rrs 241, rrs 223, rrs 414 and rrs 408 at 16.7%, 0%, 0%, 16.7% and 16.7% sensitivity, respectively, and at 96.4%, 92.9%, 82.1%, 82.1% and 71.4% specificity, respectively. This study found no significant correlation between gyrA mutations and ofloxacin resistance and also no correlation between the rrs gene and kanamycin resistance. Conclusion: These primer sequences and PCR products in our study such as gyrA and rrs might be unsuitable to detect ofloxacin and kanamycin resistance in the upper north of Thailand.
Ghulam Rasool, Muhammad Rashid Siraj, Nadia Naseem, Sameer Anjum, Waqas Lateef, A. H. Nagi
Journal of Tuberculosis Research, Volume 05, pp 168-177;

Background: The most common form of extrapulmonary tuberculosis is lymphadenitis. Lymphadenitis is considered mainly a disease of young children and has a peak age of onset at 20 to 40 years. Objectives: The purpose of this study was to detect and compare the presence of acid fast bacilli in lymph node biopsies and their touch preparations using Ziehl Neelsen and fluorescence staining. Materials and Methods: The lymph node biopsies and their touch preparations were prepared and stained with Haematoxylin and eosin to determine their morphology. Slides were stained with ZN staining and fluorescent staining technique using Auramine O and Rohdamine B to demonstrate the presence of acid fast bacilli in tissue and their touch preparations. Results: AFB was detected in 56% of biopsies and 54% of touch preparations. In addition in these cases we observed that fluorescent staining technique using Auramine O and Rohdamine B is superior to ZN stain because low magnification used in fluorescent staining technique makes it possible to scan the smear rapidly and detects the AFB as glowing spots even if it is present in small numbers. Conclusion: The results of AFB in tissue biopsies are in equivalent in their touch preparation.
M. B. Quilles, P. A. M. Balbo, M. F. Benez, L. P. Nicolellis, R. N. W. Barbosa, F. P. C. Siqueira, L. T. M. Zutin
Journal of Tuberculosis Research, Volume 05, pp 161-167;

Purpose: To highlight the diagnostic challenges of breast tuberculosis. Mammary tuberculosis is a rare disease. Its clinical and radiological characteristics are similar to other breast diseases in young women, such as granulomatous mastitis and breast carcinoma. Materials and Methods: We report a case of primary tuberculosis of a 34 years old woman who presented bilateral abscess with refractory secretion of blood and pus drainage to previous treatment with conventional antibiotic therapy of granulomatous mastitis. Results: A tuberculous mammary was observed and confirmed in the case. The diagnosis was based on imaging tests and complementary tests. Anti-tuberculosis treatment was prescribed during 6 months, and the evolution was favorable for one patient. Conclusion: Tuberculosis continued to present diagnostic difficulties, particularly in its breast tuberculosis form.
Brenda Zaragoza, Rafael Laniado-Laborín
Journal of Tuberculosis Research, Volume 05, pp 155-160;

Setting: Tuberculosis clinic in México. Objective: Since the Xpert®MTB/RIF does not detect resistance to isoniazid, our objective was to emphasize the need for additional drug susceptibility testing. Design: A prospective study. All patients with an Xpert®MTB/RIF and a positive tuberculosis culture with drug susceptibility testing were included. Results: 70 patients were included. Forty-two (60%) had a history of previous treatment for TB. Fourteen patients (20%) had a strain resistant to isoniazid (H), twelve of them (85.7%) with a history of TB treatment in the past vs. 2 (7.1%) among new cases (p = 0.028). Four patients (5.7%) had resistance to rifampin (R); three of them were previously treated cases. Additionally, six patients with a negative Xpert test (8.6%) had a positive MGIT culture; three of them were resistant to H (the 3 were poly-resistant). Two patients with a positive Xpert®MTB/RIF test without R resistance were phenotypically multidrug-resistant. Conclusion: Isoniazid resistance is associated with overall increased treatment failure, relapse, and acquired multidrug resistance in patients treated with regimens containing only first-line tuberculosis drugs. It is urgent that national TB programs implement the necessary infrastructure to complement the Xpert®MTB/RIF results with DST either by phenotypic or genotypic methods.
Journal of Tuberculosis Research, Volume 03, pp 90-96;

Tubercular infections of central nervous system commonly present with hydrocephalus, basal exudates, infarcts, tuberculomas, etc. However, rarely there are atypical lesions which can pose greater difficulty in differentiating from other lesions like tumors. This case series describes the spectrum of such lesions, with review few individual reports found in literature. Clinical presentations were weakness of limbs, slurring of speech and underlying primary tubercular focus. The age group ranged from 16 - 60 years with M:F ratio being 1:1. Spectrum of such lesions is discussed here with emphasis on the role of magnetic resonance imaging in prompt diagnosis. Thus initiating an early conservative line of management and its follow up with aversion of neurointervention which has its own inherent complications, the final outcome is a reduction in morbidity and mortality (as noted in the follow up) as well as patient cost care.
, , , Terry Lo, Henry Byabajungu, , , Emily Bloss
Journal of Tuberculosis Research, Volume 03, pp 97-106;

Setting: The Uganda National Tuberculosis Reference Laboratory (NTRL) in Kampala. Objective: The proportion of poor quality specimens received for drug susceptibility testing (DST) at the NTRL and factors contributing to poor specimen quality were assessed. Design: A cross-sectional study was conducted of sputum samples received at the NTRL from patients at high risk for multi-drug-resistant tuberculosis (MDR TB) during July-October 2013. Demographic, clinical, and bacte-riological data were abstracted from laboratory records. A poor quality sample failed to meet any one of four criteria: ≥3 milliliter (ml) volume, delivered within 72 hours, triple packaged, and non-salivary appearance. Results: Overall, 365 (64%) of 556 samples were of poor quality; 89 (16%) were not triple packaged, 44 (8%) were <3 mls, 164 (30%) were not delivered on time, and 215 (39%) were salivary in appearance. Poor quality specimens were more likely to be collected during the eighth month of TB treatment (OR = 2.5, CI = 1.2 - 5.1), from the East or Northeast zones (OR = 2.2, CI = 1.1 - 4.8), and from patients who previously defaulted from treatment (OR = 1.9, CI = 1.1 - 3.2). Conclusion: The majority of sputum samples had poor quality. Additional efforts are needed to improve quality of samples collected at the end of treatment, from East and Northeast zones, and from patients who had previously defaulted.
Hyun Je Seo, , Ji Young Park, Jong Min Kim
Journal of Tuberculosis Research, Volume 03, pp 107-112;

The proportion of non-tuberculous mycobacteria to Mycobacterium tuberculosis cultivated in the laboratory has been recently increasing. Numerous skin and soft tissue infections have been reported, while osteomyelitis is reported very rarely. A delayed diagnosis can cause a wide range of bone destruction and joint contracture, which highlights the importance of early recognition of osteomyelitis. Here we report a case of ankle osteomyelitis caused by Mycobacterium abscessus and treatment failure due to delayed diagnosis.
J. Anto Jesuraj Uday Kumar, , Hiresave Srinivasa
Journal of Tuberculosis Research, Volume 05, pp 146-154;

Background and objectives: With 2.2 million new cases every year, Tuberculosis (TB) continues to be an epidemic of large proportions in India. Conventional direct sputum smear microscopy, though limited in its sensitivity, is still the most common method of testing for TB. Newer techniques such as concentrated sputum microscopy, have shown some promise in improving this limited sensitivity. We have compared the efficacy of concentrated sputum versus the direct smear technique in 1000 sputum samples of patients suspected to be suffering from TB. Methods: A total of 1000 sputum specimens were collected for direct acid-fast bacilli (AFB) smear, concentrated AFB smear and culture from St. John’s Medical College and Hospital. 39 contaminated samples were (3.9%) omitted during the final analysis. Mycobacterial culture was used as the reference standard method for the detection of TB. Results: 184 and 198 of the 961 samples were found to AFB positive by direct smear microscopy and concentrated smear technique respectively. The measured sensitivity and specificity of direct smear microscopy were 69.86% and 95.82%, while that of concentrated smear microscopy was 76.71% and 95.96 % respectively. 33 samples found to be negative by the direct smear method turned out to be positive by the concentrated smear technique. Conclusions: Though our study suggests no significant statistical difference between the two techniques of detecting pulmonary tuberculosis, we recommend the use of the concentrated technique in centres such as ours, where facilities are already in place. In this way, the number of cases of TB that remain untreated may significantly come down.
, Ayub Ali, , Zamil Zaidur Rahim, Mahfuzur Rahman, Zahir-Ul Islam
Journal of Tuberculosis Research, Volume 05, pp 139-145;

Background: Clinical presentation of intestinal tuberculosis is varied. It is also essential to know the clinical and demographic characteristics of incidentally detected intestinal tuberculosis patient. Objective: The purpose of the present study was to find out the clinic-demographic characteristics of intestinal tuberculosis in clinically and preoperatively unsuspected laparotomies. Methodology: This cross-sectional study was carried out in the Department of Surgery at Dhaka Medical College Hospital, Dhaka from March 2002 to March 2004 for a period of two (2) years. All the patients underwent laparotomy presented without any suspicion of pulmonary or intestinal tuberculosis were included as study population. Patients who were without the history of cough, haemoptysis, antitubercular drug therapy were included. Per operative suspicion was raised due to enlarged lymph nodes in mesentery, omental masses, ileocaecal masses, suspicious growth in ileum, omental thickening, perforation suspected by tuberculosis. Biopsy was taken from suspicious lesions. Histopathology was confirmed the tubercular lesion. Results: A total number of 300 patients under laparotomy were recruited for this study of which 38 positive cases were found in the study with a percentage of 12.7%. Maximum affected age group was 21 to 30 years which was 16 (42%) cases. Male was predominant to female which was 28 (73.7%) cases and 10 (26.3%) cases respectively. Low socioeconomic people are affected more (76.3%). Most common presentation in positive cases was acute and sub-acute intestinal obstruction 20 (52.6%) followed by intestinal perforation (26.31%). Conclusion: In conclusion young age male patient is the most commonly affected intestinal tuberculosis which is frequently presented with sub-acute intestinal obstruction among the preoperatively unsuspected laparotomy patients.
Kouassi N’Guessan, Jacob Adegbele, Ibrahima Coulibaly, Natacha Kouame-N’Takpé, Hortense Seck-Angu, André Guei, Jacquemin Kouakou, Mireille Dosso
Journal of Tuberculosis Research, Volume 05, pp 129-138;

Tuberculosis represents a main concern for public health worldwide. In poor countries, the most prevalent method for bacteriological confirmation re- mains Smear Sputum Microscopy (SSM). This study objective was to assess clinical performances of Loop Mediated Isothermal Amplification for TB detection (Lamp-TB). Sputum of patients presenting symptoms consistent with tuberculosis were collected according to the National Tuberculosis Control Programme guidelines in Centre Antituberculeux de Yopougon. SSM after Ziehl-Neelsen staining and TB-Lamp were blindly performed with spot sputum specimen. Samples, transported at Institut Pasteur de Cote d’Ivoire were decontaminated according to N-acetyl-L-cystein (NALC) method. In Mycobacteria Growth Indicator Tube (MGIT), 500 μl of pellet were inoculated and incubated in MGIT 960 instrument. MPT64 antigen was detected on positive culture. Of 500 patients enrolled, 469 were included. Clinical isolates of M. tuberculosis Complex were detected for 157 (33.5%). Comparatively to culture, Sensitivity and Specificity of SSM were 86% (95% Confidence interval (CI): 81% - 91%) 96% (95%IC: 94% - 98%) respectively. TB-Lamp Sensitivity was 92% (95%CI: 88% - 96%), and Specificity 94% (95%CI: 91% - 97%). Positive Predictive Value of SSM and TB-Lamp was 91.8% and 88.8% respectively. Negative Predictive Value of TB-Lamp assay was 95.7% whereas this of SSM was 93.3%. Positive Likelihood Ratio was 15.3 for TB-Lamp and 21.5 for SSM 21.5 whereas negative Likelihood of TB-Lamp was lower than SSM. Active tuberculosis was detected in162/469 (34.5%) with TB-Lamp and 147 (31.3%) with SSM. TB-Lamp assay performances estimated from sputum samples may improve detection of active TB cases in routine.
Rekha Bansal, Parveen Kumar Sharma, Subhash Chand Jaryal, Puneet Kumar Gupta, Dinesh Kumar
Journal of Tuberculosis Research, Volume 05, pp 118-128;

Introduction: Reports indicate that fluorescent staining of smears increases sensitivity of direct microscopy; so ZN staining is being replaced with fluorescent microscopy in RNTCP in India. Chemical processing and sputum concentration may also improve sensitivity of microscopy. Objective: To compare the sensitivity and specificity of microscopy for AFB using ZN and fluorescent stains in direct and concentrated specimen with culture as gold standard. Methods: Morning sputum specimen of patients, suspected of having pulmonary tuberculosis, over a period of 6 months was subjected to direct microscopy using fluorescent stain; the same slide was over-stained with ZN stain. Same sputum sample was concentrated by Petroff’s method and subjected to fluorescent microscopy followed by ZN microscopy and finally to culture for AFB. Results: Sensitivity of fluorescent stained concentrated sputum samples was maximum and of ZN stained unprocessed sputum samples was minimum. Specificity of three of the methods was equal at 0.96 but of ZN stained concentrated sputum smears was 0.97. Sensitivity of total fluorescent stains was 0.85 (Specificity 0.96) and sensitivity of total ZN stained smears was 0.80 (Specificity 0.96). Discussion: We used same smear for fluorescent and ZN stains, so smear related variability is decreased. Blinding for microscopy was practically complete. Conclusion: The sensitivity of sputum microscopy for AFB can be increased by concentrating the sputum and using fluorescent microscopy. The specificity remains high in all the methods.
S. Maharjan, A. Singh, D. K. Khadka, M. Aryal
Journal of Tuberculosis Research, Volume 05, pp 106-117;

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.
, Aniefon Umana, Nta Okoi, Francis Akpan, Carlistus Enyuma
Journal of Tuberculosis Research, Volume 03, pp 59-61;

Tuberculosis has traditionally been found to occur with weight loss or at least failure to gain weight. Atypical and unusual presentations of various types of tuberculosis have been reported but limited data is available on tuberculosis in well-nourished children with no weight loss. Two case reports from our experience highlight well-nourished children with histologically diagnosed tuberculosis that presented with atypical symptoms and no evidences of weight loss. The usefulness of histological diagnosis cannot be overemphasized. This report aims to highlight this unusual presentation of tuberculosis so as to increase the index of suspicion for early diagnosis and hence, prompt treatment of tuberculosis in this group of children.
D. R. Gayathri Devi, H. B. Mallikarjuna, , S. Vishnu Prasad
Journal of Tuberculosis Research, Volume 03, pp 54-58;

Mycobacterium abscessus, a rapidly growing and potentially pathogenic Mycobacterium, is an environmental contaminant and is commonly found in tap water supplies. We report a case of M. abscessus meningitis following VP shunt insertion. A 9-year-old male patient with previous history of aqueductal stenosis and hydrocephalus with VP shunt in situ, presented with pain abdomen of 10 days duration. Investigations revealed multiple mesenteric lymph nodes with impacted VP shunt tip within the omentum. Ascitic fluid and CSF tap showed Acid-Fast Bacilli, later confirmed to be M. abscessus. The patient was treated with Clarithromycin and Amikacin, leading to resolution of the infection. To the best of our knowledge, this is the first reported case of M. abscessus meningitis in an immunocompetent individual. We discuss the possible sources of infection and therapeutic challenges. It is of utmost importance to consider, with high index of suspicion, nontubercular Mycobacteria as the causative organism in patients, who do not respond to regular anti-tubercular regimen.
, K. C. Pua
Journal of Tuberculosis Research, Volume 03, pp 50-53;

Background: Tuberculosis (TB) of the nose and nasopharynx are rare localizations for tuberculosis to manifest. Aim: We hope to present a case of tuberculosis of the nasopharynx and its rare presentation. Case presentation: This patient presented with a long standing history of headache and neck pain prior to being seen. Imaging showed a mass at the nasopharynx and a biopsy con-firmed tuberculosis. Patient was initiated on anti-tuberculosis therapy with improvement in her symptoms on follow up. Conclusion: A high index of suspicion is imperative for early diagnosis.
Onyemocho Audu, Shember AgelaIgbabul, , Istifanus A. Joshua, Gabriel O. Anefu, Samson Ejiji Isa
Journal of Tuberculosis Research, Volume 05, pp 95-105;

Background: Most researches on the correlate of Tuberculosis (TB) treatment outcomes place emphasis on sociodemographic characteristics of the patients, Human Immunodeficiency Virus status and CD4+ count of patients and nutrition among others. This study assessed the effect of delay in commencement of anti-TB regimen on the treatment outcomes of all Tuberculosis patients treated between 2011 and 2014 in three directly observed treatment short course centres in Benue State, Nigeria. Methodology: A retrospective cohort study with convenient sampling technique was used for all registered Tuberculosis patients enrolled for treatment within the reviewed period. Chi-square (χ2) test was used for test of association between the independent variables and the main outcomes of the study, with statistical significance set at p-value of 5%. Results: Of the total 1711 cases reviewed, the males to females ratio was 3.9:1. The mean age for the males’ patients was 39.0 ± 15.3 years and the females 33.7 ± 14.2 years. Majority of the patients were new pulmonary Tuberculosis cases and they commenced their treatment after 3 weeks of diagnosis. Higher failure and death rate were reported amongst the patients who commenced their treatment late (78.7% and 42.5% respectively). The relationship between the treatment outcome and the time of commencement of anti-TB drug regimen was statistically significant (p < 0.005). Conclusions: Commencement of anti-TB drugs in all diagnosed Tuberculosis patients is an important correlate that must be addressed in order to achieve the global goal of reducing Tuberculosis prevalence to the level at which it will no longer constitute a public health problem in Nigeria.
El Tigani-Asil El Tigani Ahmed, Abdulkhalig Babiker Hassan, Adam Dawoud Abakar
Journal of Tuberculosis Research, Volume 05, pp 77-80;

The study was aimed to investigate the pathological changes of condemned lungs of dromedary camels in the Sudan abattoirs using conventional H & E and Zeihl Neelson (ZN) staining procedures. Proliferative granulomatous reaction was demonstrated in one H & E stained lung section which was characterized by focal fibrosis and infiltration of mononuclear cells resembled to tuberculous lesions. While ZN stained sections demonstrated acid fast rod in one pulmonary associated lymph node. These lesions were evidenced presence of tuberculous mycobacteria in camel tissues and recommended further deep investigation of tuberculosis among camels in the Sudan.
Afshan Khurshid, , Einar Heldal, , , , Amanullah Ansari, Kashif Anwar, Ejaz Qadeer,
Journal of Tuberculosis Research, Volume 05, pp 81-86;

To identify missing childhood Tuberculosis (TB) cases, “screeners” (hospital-based health workers trained to screen accompanying contacts of TB patients for symptoms) were introduced in eight tertiary care hospitals of Sindh, Pakistan in 2013. There was a 55% increase in childhood TB notifications in 2014 compared to 2012 in facilities with screeners (n = 8) compared to 40% increase in facilities without screeners (n = 22). This apparent association disappeared when stratified by presence of “trained pediatrician” whose introduction was associated with a massive increase in notifications while transfer was associated with a marked decrease. In conclusion, screeners were not associated with increase in pediatric TB case notifications.
, Makoto Kittaka, Keiji Mouri, Shigeki Kato, Mikio Oka
Journal of Tuberculosis Research, Volume 05, pp 87-93;

Objective: To investigate the clinical characteristics of miliary tuberculosis experienced in our tertiary hospital without a tuberculosis isolation room. Materials and Methods: We obtained a definite diagnosis of tuberculosis for 72 patients in our tertiary hospital between January 2010 and September 2016. There were six patients (8.3%) who were diagnosed with miliary tuberculosis following the isolation of Mycobacterium tuberculosis from several organs, and we analyzed the clinical findings. Results: The average age of the six patients with miliary tuberculosis was 74 years old (3 males and 3 females). All patients had underlying diseases and immunosuppressive treatment was performed for three patients. The detection methods were based on clinical symptoms such as high fever in all patients. Concerning the laboratory findings, three patients showed a negative or indeterminate response for interferon-gamma release assays (IGRAs). Bronchoscopic examinations were performed for five of six patients soon after admission and a definite diagnosis was obtained. Although treatment according to the American Thoracic Society (ATS) guidelines was performed for all patients, three of the six died due to complications or worsening of miliary tuberculosis. Conclusions: Patients with miliary tuberculosis experienced in a tertiary hospital were frequently detected among patients receiving immunosuppressive treatment for a long time. Because these patients showed a rapid progressive clinical course, it is thought to be important to perform bronchoscopic examination proactively for patients suspected of miliary tuberculosis on radiological findings to make an appropriate early diagnosis and start treatment.
Saima Abdalrhman Osman, Walla Saeed Eltahir Saeed, Ahmed Mudawi Musa, Brima Musa Younis, Abd Elgadir Ali Bashir, Fath Elrahman Mohamed Idris, Ala Eddin Hassan Ahmed,
Journal of Tuberculosis Research, Volume 05, pp 69-76;

A third of the world’s population is latently infected with TB with an increased risk of developing active TB. Household contacts (HHCs) of pulmonary TB cases are at a greater risk of developing disease. Early identification and treatment of latent TB infected individuals may reduce progression to active TB. This study aimed to determine latent TB infections (LTBI) point prevalence among HHCs and community contacts (CCs) using Tuberculin Skin Test (TST) and whole blood IFN-γ release assay in an area of high TB prevalence. In a prospective, longitudinal and community-based study and following informed consent, 768 volunteers (HHCs n = 245; CCs n = 523) were enrolled. Tuberculin Skin Test (TST), whole blood stimulation with PPD and IFN-γ levels determination using ELISA were performed. Mean ages of HHCs and the CCs were not significantly different (HHCs 35.6 ± 15.7 and CCs 30.6 ± 11.7 years; p = 0.99), with a Male:Female ratio of 1:2. Mean recruitment TST indurations were 4.6 ± 5.5 mm and 2.8 ± 3 mm for HHCs and CCs respectively (p = 0.000). Follow-up (Day 614) mean TST indurations increased significantly to 9.1 ± 7.2 mm and 4.4 ± 3.2 mm for HHCs and CCs respectively (p = 0.001). Using TST indurations ≥ 10 mm, LTBI point prevalence for HHCs and CCs was significantly different (HHCs 461/1000 and 367/1000 individuals, p = 0.03). The mean IFN-γ levels for HHCs and CCs at recruitment day (Day 0) were 0.66 ± 0.17 IU/ml and 0.06 ± 0.04 respectively. The mean of IFN-γ production levels dropped significantly at Day 614 for HHCs and CCs to 0.66 ± 0.15 IU/ml and 0.02 ± 0.02 respectively (p = 0.03) (p = 0.00001). Recruitment LTBI point prevalence using IFN-γ level ≥ 0.35 IU/ml for HHCs and CCs was 440/1000 and 203/1000 respectively (p = 0.000000001). No correlations between TST indurations and IFN-γ levels were detected among HHCs or CCs (p > 0.05). TST is a simple, efficient and cheap technique for LTBI diagnosis and triaging individuals for treatment.
Dwi Yuni Nur Hidayati, Hidayat Sujuti, Laksmi Wulandari, Alan Darma Saputra, Giovani Anggasta Santoso
Journal of Tuberculosis Research, Volume 05, pp 58-68;

Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis. Mycobacterium tuberculosis will form the primary focus or Ghon focus in the lungs of infected people. The primary focus can break and get into the bloodstream and/or lymph to the entire body, including the central nervous system, especially the brain. Tuberculosis infection in the brain can cause microglia secrete inflammatory factors such as TNF-α and IL-1β is emerging as the body’s immune response. The factors that can trigger microglia to secrete iNOS (Inducible Nitric Oxide Synthase) in order to protect the brain from attacking bacteria. iNOS is shown to have an important role in tuberculosis infection in the brain. TNF-α is a pro-inflammatory cytokine which is mostly produced by macrophages/microglia through several mechanisms. Therefore, to investigate how the expression of TNF-α and iNOS in the brain tissue of the mice is not infected with tuberculosis, tuberculosis infection with an incubation period of 8 weeks and 16 weeks. This study is a semiquantitative study by comparing the amount of expression of TNF-α and iNOS and all three groups of samples with treatment as has been mentioned. The expressions observation of TNF-α and iNOS in brain cell tissue of mice was conducted using immunohistochemical staining, and was seen in a microscope with a magnification of ×100. Brain cells that express TNF-α and iNOS are brown core, cytoplasm and cell walls. The results were obtained by the longer exposure to infection of the higher expression of TNF-α (r > 0688) and the expression of iNOS decreased (–0.993).
J. Anto Jesuraj Uday Kumar, Hiresave Srinivasa, Justy Antony Chiramal
Journal of Tuberculosis Research, Volume 05, pp 44-57;

India tops the global list for Drug resistant Tuberculosis, but inadequate and expensive laboratory culture techniques have led to delay in the diagnosis and treatment. We studied the potential of an alternative method which could be cost-effective by combining the drugs in the same tube for identification of drug resistance. Drug Susceptibility Test (DST) results of 1000 sputum samples are got from suspected TB patients against INH (isoniazid) and Rifampicin by two techniques: a) a modified technique with both drugs in the same MGIT tube and b) a standard technique with the antibiotics in separate MGIT tubes for the diagnosis of MDR-TB (Multidrug Resistant). 39 samples were contaminated and were excluded from final analysis. 198 were smear positives by the concentrated Ziehl-Neelsen’s staining method. 219 were found to be culture positive out of which 195 were identified as M. tuberculosis complex. 40 (20.5%) strains were identified as MDR-TB by the conventional method and 39 were picked up by the modified DST. INH and Rifampicin mono-resistance accounted for 32 (16.4%) and 4 (2%) respectively. 99% concordance was observed between the two tests in categorizing MDR-TB. Similarly modified technique with combination of the second line Antibiotics-Ofloxacin, Kanamycin and Capreomycin was applied on the identified MDR strains in a stepwise manner. 6 (15%) were identified as Pre-XDR strains and 2 (5%) were found to be XDR-TB strains. This study implies that combining drugs in the same tube may be an equivalent and possibly a cost-effective alternative which needs to be explored further.
Loukia Aketi, Joseph Shiku Diayisu, Zacharie Kashongwe, Grâce Nkabikueni, Patrick Kayembe Kalambay, Jean-Marie Kayembe
Journal of Tuberculosis Research, Volume 05, pp 30-43;

Introduction: To participate effectively in the fight against tuberculosis (TB), mothers need to have a good knowledge of TB and its prevention. The objective of this study was to evaluate the knowledge of mothers about TB and Bacillus Calmette Guérin (BCG). Methods: This was a cross-sectional survey performed from September to December 2015 in 4 health care facilities of Kinshasa. It concerned mothers of children who received BCG vaccine. The frequencies and chi-square of Pearson were used to report results. Results: A total of 380 couples of the children and their mothers were recruited. The median age of children was 16 months (ranges: 6 days to 59 months); 224 (58.9%) of them received BCG during the period recommended; 62 (16.3%) experienced a side effect. There was a significant association (p = 0.00) between sides effects and the delayed vaccination. The average age of the mothers was 29.3 ± 6.4 years; 352 (92.6%) had heard about TB; 28 (7.4%) never heard about it; 168 (44.2%) knew that TB is a contagious disease; only 111 (29.2%) knew the mode of transmission; 87 (22.9%) did not know any signs of TB, and 54 (14.2%) knew about prevention with the BCG vaccine. Factors significantly associated with the mothers’ lack of knowledge were a low level of education (p = 0.01), young age (p = 0.02), and place of residence (p = 0.04). Conclusion: There is an urgent need to improve the education of the population, particularly those who lives in poor conditions and who are uneducated.
, A. Zinebi, Y. Touibi, K. Moudden, N. Lahmidani, B. Zainoun, M. El Baaj
Journal of Tuberculosis Research, Volume 05, pp 23-29;

Purpose: To highlight diagnostic challenges of pseudotumoral abdominal tuberculosis. Materials and methods: Three cases of pseudotumoral abdominal tuberculosis were compiled in our department between 2014 and 2015. They were aged 34 years, 42 years and 61 years respectively. They were immunocompetent and had no personal or family history of tuberculosis. Clinical presentations were non-specific, represented by abdominal pain and weight loss in the three patients and chronic diarrhea in one patient. Abdominal ultrasound and computed tomography CT were performed in all patients. Abdominal MRI was performed in one case as well as a colonoscopy. Results: Retroperitoneal tuberculosis and colic tuberculosis were noted in the 1st and 2nd case. Macro-nodular and biliary hepatic tuberculosis was retained in the third case. The diagnosis was based upon histopathology in the 3 cases showing tubercular granuloma with caseation. Anti-tuberculosis therapy was prescribed for 6 months. Evolution was favorable in all patients. Conclusion: Tuberculosis continues to present diagnostic difficulties, particularly in its pseudo-tumoral form, even in endemic tuberculosis countries like ours.
Farzad Firuzi Jahantigh, Hakimeh Ameri
Journal of Tuberculosis Research, Volume 05, pp 13-22;

According to the World Health Organization, Tb is the biggest cause of death among the infectious diseases. Due to the high percentage of people with tuberculosis infection and the high number of death among these patients, this study is a prospective study aimed to categorize and find the relationship between different clinical and demographic characteristics. The study was conducted on 600 patients from Masih-e-Daneshvari tuberculosis research center during 2015-2016. The K-Means clustering data mining algorithms and decision trees are used to perform the categorization and determine common indicators among patients. 2 clusters according to Dunn index were chosen as the optimal clusters. Common factors between clusters are provided in detail in the findings section. According to the results of this study, the most important factors identified by the clustering include hemoglobin, age, sex, smoking, alcohol consumption and creatinine. The RBF neural network tree has 98% accuracy. According to the results of this study, the most important factors identified are sex, smoking, alcohol consumption and WBC, albumin.
Aymen Awad Abdelhaleem, Almonther Abdallah Hershan, Pradeep Kumar Agarwal
Journal of Tuberculosis Research, Volume 05, pp 1-12;

Purpose: To evaluate diagnostic accuracy of IS6110 insertion genes, hsp65, and Xpert MTB/RIF for rapid diagnosis of pulmonary tuberculosis. Methods: Sixty patients, medically reported HIV negative, clinically suspected of having pulmonary tuberculosis, were included in this study, and consented before enrolment. Sputum samples were gathered once, and tested by smear for Acid Fast Bacilli (AFB). Cultured in the Loewenstein-Jensen (LJ) medium for M. tuberculosis growth, M. tuberculosis DNA was detected by conventional PCR targeting IS6110, and hsp65 genes using specific primers, and automated nested real-time PCR targeting rpoB gene. Sensitivity, specificity and diagnostic accuracy were calculated for each method compared to culture. Results: Compared with culture as reference method, smear, IS6110, hsp65, and Xpert MTB/RIF had sensitivity 77.14%, 100%, 100%, and 100%, specificity 92%, 96%, 96%, and 96.97%, and diagnostic accuracy 83.33%, 98.33%, 98.33% and 98.21% respectively. Molecular diagnostic methods had the highest diagnostic accuracy, whereas smear had the lowest. No statistical significance, (p value > 0.05) was detected between the patients’ demographic data and the presence or absence of TB infection. Conclusion: The diagnostic accuracy that we got from the molecular methods, confirmed the diagnostic value of molecular detection of M. tuberculosis in pulmonary cases, supporting the application of automated and conventional PCR in rapid analysis. Smear could be more efficient when used for treatment monitoring. Combination between one-molecular techniques with smear as a routine method could be valid for rapid diagnosis of TB.
Aketi Loukia, Shiku Diayisu Joseph, Kashongwe Zacharie, Lay Gertrude, Kibadi Kapay, Kayembe Kalambay Patrick
Journal of Tuberculosis Research, Volume 04, pp 235-248;

Setting: The epidemiology of tuberculosis (TB) among children in the Democratic Republic of Congo (DRC) is not well known. Objective: This study aimed to describe the trends in TB epidemiology among children in the DRC and to compare these trends in children and adults. Design: Data from the National TB program, the WHO Global TB Report, and a demographic survey of health in the DRC were retrospectively analyzed. The study period was from 1995 to 2014. The notification rate, absolute incidence and incidence rate of TB per 100,000 population were reported. Results: In 2014, 12,785 (12.6% of adult cases) TB cases were reported in children and 101,303 in adults. Among children, 3438 (26.89%) had PTB+; 2828 (22.11%) had PTB–; and 6519 (50.98%) had extrapulmonary TB (EPTB). Children under 5 years had a lower reported prevalence of TB (184 cases). The incidence rate per 100,000 population was 10 in children and 181 in adults. The TB incidence decreased between 2010 (11.47) and 2014 (10.46). The proportion of children in overall cases of PTB+ was 4% to 5% in all districts. Conclusion: Caring for childhood TB remains a challenge in the DRC. Improved diagnostic procedures and effective training of providers who care for childhood TB are needed.
Chipo Mufudza, Senelani D. Hove-Musekwa,
Journal of Tuberculosis Research, Volume 04, pp 191-212;

Enhancement of the Human Immunodeficiency Virus (HIV) specific cytotoxic T-cells mechanisms in an HIV-1 and Mycobacterium tuberculosis (Mtb) co-infected individual seems to improve the clinical picture of an individual by reducing Acquired Immuno Deficiency Syndrome (AIDS) state progression rate. In this paper, we develop a system of deterministic differential equations representing the immune cells involved in an HIV-1 and Mtb co-infected individual. Results show that although the non-lytic arm of the HIV-1 cytotoxic T-cells affects the co-infection dynamics more than the lytic factors, a combination of both factors results in a more positive reduced progression to the AIDS state. This is due to the increased protection of the CD4+ T-cells by the CTL mechanisms by further reducing infections and replications by the HIV. Thus, HIV-1 specific CTLs mechanisms’ involvement is here recommended to be part of a solution to the HIV and Mtb co-infection problems.
  Amreen, Nadeem Rizvi
Journal of Tuberculosis Research, Volume 04, pp 183-190;

Objective: The aim of present study was to determine the frequency of depression and anxiety among tuberculosis patients. Methods: It was a descriptive study that had investigated the co-morbidity of depression and anxiety among tuberculosis patients with reference to gender. This study was conducted in Jinnah Post Graduate Medical Centre―Chest ward (TB clinic) from July 2014 to September 2014. Hundred diagnosed patients of tuberculosis (50 males and 50 females) were randomly selected. Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Questionnaire (GAD-7) were used to assess the level of anxiety and depression. Results: Findings indicated that 56% tuberculosis (TB) patients had moderate to severe level of depression, whereas 65% TB patients had moderate to severe level of anxiety. Female patients had significantly high prevalence of depression as compared to males (t = −2.173, P < 0.05). Similarly, prevalence of anxiety was also significantly higher in female patients (t = −3.468, P < 0.05). Conclusion: Likelihood of depression and anxiety was frequent in tuberculosis patients. However, better management of these psychiatric morbidities may improve treatment adherence, illness perception and patient coping skills.
, Tyson Volkmann, Sushma Cornelius, Sugata Mukhopadhay,   MejoJose, Kaushik Mitra, , John E. Oeltmann, Sidhajyoti Parija, Aslesh Ottapura Prabhakaran, et al.
Journal of Tuberculosis Research, Volume 04, pp 213-219;

Introduction: Poverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome. Methods: This was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death). Results: Of 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51; 95% Confidence Intervals: 0.30 - 0.86). Conclusion: Under programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line.
Yogita Mistry, Sangita Rajdev, Summaiya Mullan
Journal of Tuberculosis Research, Volume 04, pp 227-234;

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum; 33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value < 0.01. MDR cases were 2% out of 350 samples. Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.
Mohammad Mahmudul Huda, Mohammad Taufiq, Abdullah Yusuf, Mohammad Rezwanur Rahman, Ferdousy Begum, Mohammed Kamal
Journal of Tuberculosis Research, Volume 04, pp 220-226;

Background: Clinical and demographic features are important for the tuberculous lymphadenitis patients for treatment. Objective: The purpose of the present study was to see the clinical and demographic features of tuberculous lymphadenitis patients. Methodology: This cross-sectional study was done at the Department of Pathology at Banghabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2009 to March 2011 for a period of nearly two years. All the patients, irrespective of age and sex with the clinical features, suggestive of tuberculous lymphadenitis and later on, proved to be the same histologically, were selected for the study purposively. Relevant information was recorded in a prescribed data sheet and histomorphological findings were recorded accordingly. In cases where fresh specimen was available, caseous portion of lymph node was sent for culture. Fite Faraco staining was also done on lymph node sections in all cases. Result: A total number of 50 tuberculous lymphadenitis patients were recruited for this study. Among this study population, the age of cases ranged from 12 years to 65 years with a mean age of 26.22 ± 2.52 years. Male and female ratio was 1:1.38. Besides lymphadenopathy, 45 patients had low grade fever; 32 patients had weight loss and 18 patients had cough. Among 50 cases of lymph node tuberculosis cervical lymphadenopathy was 41 (82.0%) cases; 6 (12.0%) cases had supraclavicular lymphadenopathy; 2 (4.0%) cases had inguinal lymphadenopathy and 1 (2.0%) had axillary lymphadenopathy. The mean duration of presentation of lymphadenopathy with standard deviation was 7.06 ± 1.6 months. Thirty eight patients (76.0%) had lymphadenopathy for less than 12 months. Conclusion: In conclusion, young age group people are most commonly affected by tuberculous lymphadenitis with the predominance of female and most of them are presented with low grade fever and weight loss.
, Spencer S. Davis, Gordon B. Lindsay, Elena Khomitch
Journal of Tuberculosis Research, Volume 04, pp 111-121;

Introduction: Historical analysis of health data indicates that the majority of the decrease in tuberculosis mortality during the past century was caused by improved social conditions and public health interventions. The purpose of this study was to assess lay public perceptions regarding why tuberculosis declined. Materials and Methods: A nationally representative sample of 705 adults was surveyed to identify their perceived reasons for the decline in tuberculosis mortality in the 20th century. Open- ended questions and responses were coded and placed into eight categories. Results: Approximately 52% of decreasing tuberculosis mortality was attributed to “modern medicine,” and 220% to “vaccination.” Comparatively few of the respondents attributed decreased tuberculosis mortality rates to public health or improvements in social health determinants of health. Males gave more credit to modern medicine and public health, with less to vaccination; the other racial group gave more credit to public health and less to modern medicine; Hispanics gave more credit to modern medicine and less to vaccinations; and the higher income groups gave more credit to vaccinations and public health, but less to modern medicine. Conclusion: The public overly attributes modern medicine as the primary cause of declining tuberculosis mortality rates, the second leading cause of death in the United States during the early 1900s, and gives little credit to the critical role played by public health and improved social conditions. These misperceptions may hinder societal efforts to address and fund important social determinants of health and public health interventions.
Yogita Mistry, Sangita Rajdev, Summaiya Mullan
Journal of Tuberculosis Research, Volume 04, pp 147-154;

Tuberculosis is one of the most important infectious diseases in our country. Also nosocomial infection by tuberculosis can occur, which can be prevented by implementing simple, effective and affordable tuberculosis infection control measures in health care facilities. To evaluate the effectiveness of infection control measures, such study was planned. Questionnaires were administered to all doctors, healthcare workers and servants working in outdoor and indoor department of tuberculosis at tertiary care hospital to assess the knowledge, attitudes and practices on prevention and control of Tuberculosis infection. A scoring system was devised to grade them. One-time audit was also done in outpatient and inpatient department. The analysis showed scoring of poor for doctors, good for nurses and poor forward aids. There is a need to develop strategies for training of health care workers on regular basis in order to reduce the incidence of nosocomial infections. Audit result shows a good level of environmental control measures. Better knowledge, attitude and practices are helpful for the prevention and control of tuberculosis. Also environmental control measures are helpful to prevent infection.
Fatima Osman, Farzana Ismail, Ayman Osman, Shaheed Omar, , Nazir Ismail
Journal of Tuberculosis Research, Volume 04, pp 155-172;

Background: Pyrazinamide (PZA) is one of the most important drugs for tuberculosis (TB) treatment, however, its susceptibility is not routinely tested. High-resolution melting (HRM) curve analysis has been widely used for many applications. In this study, HRM assay was developed and evaluated for the detection of PZA resistance in Mycobacterium tuberculosis clinical isolates. Methods: Ninety five M. tuberculosis clinical isolates with different susceptibility patterns to anti-TB drugs were used to evaluate this assay. Isolates were phenotypically (Bactec MGIT 960) and genotypically (HRM and pncA gene sequencing) analysed for PZA resistance. Results: Bactec MGIT 960 analysis revealed that 29 of the 95 M. tuberculosis isolates were PZA resistant. In comparison to the Bactec MGIT 960, HRM showed a sensitivity of 47.7% and specificity of 74.6%, and the overall agreement between the two methods was 68.4%. Based on DNA sequencing, a correlation of 0.67 (significant at p-value < 0.05) between phenotypic resistance to PZA and pncA mutations was observed. PZA resistance was strongly associated with multi-drug resistant (MDR)-TB as it was shown in 79.3% of the MDR isolates included in the study. Conclusion: HRM is simple and useful for screening clinical M. tuberculosis isolates for PZA resistance, however, further modifications to improve its performance are required.
Journal of Tuberculosis Research, Volume 04, pp 173-182;

Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined risk factors associated with poor response to initial treatment with four anti-TB drug regimens or three drug regimens with steroids as adjuvant therapy. Methods: This study analyzed medical records from two tertiary hospitals in Busan, Korea, between January 2009 and March 2012. The subjects were non-human immunodeficiency virus (HIV)-infected patients aged ≥16 years with clinical CNS TB. The subjects were divided into two groups according to response to treatment. Results: In totally, 52 patients with CNS TB were included. Of these, 14 (26%) and 38 (73%) showed poor and good responses, respectively. Of the patients with poor response, nine had stage III disease (64.3%) according to the British Medical Research Council (BMRC) staging system. A significantly higher proportion was seen in the good response group (p < 0.05). Patients with positive cerebrospinal fluid (CSF) acid-fast bacillus (AFB) culture, positive sputum AFB culture, positive CSF TB polymerase chain reaction (PCR) results, and brain tuberculoma had poorer responses (p < 0.05). Multivariate analysis to determine risk factors associated with poor response to anti-TB therapy revealed that a poor response was associated with stage III clinical signs upon diagnosis (odds ratio [OR] 32.122; 95% confidence interval [CI] 2.221 - 464.605), positive sputum AFB culture (OR 13.624; 95% CI 1.066 - 174.149), and tuberculoma on brain images (OR 45.714; 95% CI 1.893 - 1104.018). Conclusions: The results demonstrate the importance of identifying the severity of CNS TB and promptly administering anti-TB drugs. It is necessary to perform drug susceptibility testing for anti-TB drugs. Further studies are needed to confirm the correlations between risk factors associated with poor response and anti-TB drug resistance and the other risk factors.
G. Kazdaglis, K. Manika, P. Ioannidis, D. Papaventsis, E. Vogiatzakis, E. Papakala, M. Panopoulou, A. Galatas, A. Melidou, I. Kioumis, et al.
Journal of Tuberculosis Research, Volume 04, pp 92-97;

Tuberculosis (TB) remains one of the world’s deadliest diseases. Increasing rates of drug-resistant tuberculosis in Eastern Europe, Asia and sub-Saharan Africa now threaten to undermine the gains made by worldwide tuberculosis control efforts. The region of Macedonia in North Greece is an entrance gate of thousands of immigrants, moving mainly from East European countries with high tuberculosis prevalence to Greece and the whole Europe. Our study determines the drug susceptibility pattern of new TB cases in the region of Macedonia, Greece. A total of 63 M. tuberculosis strains were isolated by cultivation between January 2012 and December 2014 in Macedonia, North Greece. After microscopic examination with Ziehl-Neelsen staining, clinical samples were simultaneously tested by two methods: conventional culture method on the Löwenstein-Jensen (L-J) slants for 8 weeks (at 370°C) and molecular method Genotype MTBDR plus (Hain-Lifescience). According to the study results, 2 out of 63 strains (3.2%) were resistant to both isoniazid (INH) and rifampicin (RMP). Additionally, 3 strains (4.8%) were INH mono-resistant. Statistical analysis demonstrated that there was no statistically significant difference in presence of resistance according to patients’ gender or origin (Greeks or immigrants). It is clear that the implementation of an efficient nationwide system for the surveillance, diagnosis and treatment of TB is essential. The best strategy in order to control, and prevent TB includes, first of, all a rapid diagnosis and initiation of treatment, something which is the most important for public health.
, Singarajipura Anil, Balaji Naik, Tyson Volkmann, Karuna D. Sagili, Jayachamarajapura S. Akshatha, Shashidhar Buggi, Manchenahalli A. Sharada, Sudhendra Kulkarni, Vineet K. Chadha, et al.
Journal of Tuberculosis Research, Volume 04, pp 105-110;

We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment; the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on antiretroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.
Abiodun Hassan, Richard Olukolade, Queen Ogbuji, Audu Onyemocho, Lucia Okwuonye, Shember-Agela Igbabul, Josephine Okechukwu, Oluremilekun Kusimo, Adewale Osho, Kehinde Osinowo, et al.
Journal of Tuberculosis Research, Volume 04, pp 122-133;

Background: Despite the availability of highly effective treatment for decades, Tuberculosis (TB) remains a major health problem in Nigeria due to the increasing association between HIV and TB observed over the past three decades when HIV was discovered. However, the proportion of TB and or TB/HIV co-infected patients who have successful TB treatment outcome is not well known. This study determined the treatment outcome of TB/HIV co-infected patients with HIV negative patients in two states in Nigeria. Materials and Methods: A retrospective study of secondary data from eight Directly Observed Treatment Short (DOTS) course and Anti- Retroviral Therapy (ART) service providers in Benue and Federal Capital Territory (FCT), Nigeria, was carried out. The period under review covers January, 2010 to December, 2013. Results: Out of the total 5266 TB cases reviewed, the HIV prevalence rate was 52%. They were predominantly (53.3%) male with mean age of 34.4 years (SD = 15.1 years). More than two-third (72.5%) of HIV-negative patients had successful treatment compared to 1718 (62.7%) HIV-positive patients. Of the 2334 HIV co-infected patients, 19.5% defaulted, 11.5% had died, 5.6% were transferred out and 0.7% failed treatment compared to HIV-negative patients amongst whom 18.3% defaulted, 3.6% died, 3.9% were transferred out and 1.6% failed treatment (p < 0.05). TB/HIV co-infected patients with baseline CD4 of ≥300 cell/mm3 are more likely to have successful treatment outcome {OR-1.541 (95% CI = 1.030 - 2.305) p = 0.035}. Patients ≥45 years old and those not on Co-trimoxazole Preventive Therapy (CPT) are more likely to have unsuccessful treatment outcome {OR-1.022 (95% CI = 0.643 - 1.488) p = 0.918 and OR-1.306 (95% CI = 0.956 - 1.555) respectively. Conclusion: The favourable treatment outcome of HIV-negative patients is more than that of HIV-positive patients and the most probable predictable factor responsible is the CD4 count of patient; indicating that TB/HIV co-infection has remained a major public health problem in Benue state and FCT. Hence there is the need for sustained strengthening and expansion of the national TB/HIV programmes.
Monji Koga, Masaki Fujita, Shinichi Imafuku
Journal of Tuberculosis Research, Volume 04, pp 134-139;

Tuberculosis (TB) is a major public health problem worldwide and a large number of fatal cases are still reported. Immunocompetent individuals are naturally susceptible to TB, and immunocompromised patients have a greater risk of infection. Although patients with adult T-cell leukemia/lymphoma (ATL) are in an immunosuppressed condition, there is only one reported case of TB accompanied with ATL in the English- language literature in the field of dermatology. Here, we report two patients with chronic-type ATL infected with TB manifesting as cutaneous solitary masses. Case 1 was a 58-year-old woman diagnosed with lumbar abscess with pulmonary TB. Case 2 was an 84-year-old woman diagnosed with tuberculous lymphadenitis in the left cervical region. It is important to raise the differential diagnosis of TB and perform tissue culture for acid-fast bacilli as well as Interferon-Gamma release assay test when dermatologists encounter mass lesions in patients with ATL.
Muatsim Ahmed Mohammed Adam, Hamdan Mustafa Hamdan Ali, Eltahir Awad Gasim Khalil
Journal of Tuberculosis Research, Volume 04, pp 98-104;

Drug susceptibility testing (DST) plays a pivotal role in TB patients’ management leading to the selection of most effective drugs. This study aimed to determine resistance patterns to first line anti-TB drugs in Mycobacterium tuberculosis isolates from re-treated patients from Sudan. A total of 239 sputum specimens were collected from smear positive re-treatment TB patients during the period from July 2009 to July 2010. Specimens were pre-treated according to Petroff method. The recovered isolates were tested for sensitivity to first line anti-TB drugs by the 1% proportion method. One hundred and forty three (143/239, 59.8%) mycobacterial isolates were successfully recovered. The majority (98.6%, 141/143) of the isolates were Mycobacterium tuberculosis complex strains. Two strains (2/143, 1.4%) were identified as RIF/INH-resistant MOTT, while fifty four isolates (38.3%, 54/141) were MDR. Multi- drug resistant Mycobacterium tuberculosis complex (MDR-TB) among re-treatment patients from national referral centers for tuberculosis diagnosis and management was considerably high in the study isolates.
Yoshihiro Kobashi, Masaaki Abe, Keiji Mouri, Shigeki Kato, Mikio Oka
Journal of Tuberculosis Research, Volume 04, pp 141-146;

We encountered two cases of pulmonary M. kansasii disease in two women without underlying diseases in our hospital. Case 1 was a 52-year-old woman who visited with an abnormal chest shadow. She showed nodular and linear shadows with bronchiectatic changes and small cavities in the left upper lobe and lingula, and was diagnosed with pulmonary M. kansasii disease because M. kansasii was isolated from her bronchoscopic specimens. Case 2 was a 33-year-old woman who visited with a productive cough. She showed several cavity lesions in the right lung, and was diagnosed with pulmonary M. kansasii disease from several isolated sputum samples. Combination therapy using INH, RFP, and EB was effective treatment for the two cases. Because pulmonary M. kansasii disease in previously healthy women shows various radiological patterns, it was considered important to perform acid-fast bacilli examination using clinical specimens in order to decide on the appropriate treatment methods.
Ssakher M. AlOtaibi, Abdullah F. Almoshadq, Hosam A. Alghanmi, Fetoon Aljuiad, Yasmin R. Soliman, Abdulmajeed T. Alzuair, Osama A. Alzahrani, Abdulrahman A. Algarni, Malak Y. Ali
Journal of Tuberculosis Research, Volume 04, pp 81-91;

SETTING: Millions of pilgrims visit Makkah (Mecca), Saudi Arabia, from regions of endemic tuberculosis. Little consideration has been given to the potential impact of this disease on the local population. OBJECTIVES: To assess knowledge about TB among residents of Makkah and Jeddah (Makkah’s principal travel gateway). METHODS: A cross-sectional survey of 1004 residents. Data were analyzed by gender. RESULTS: Spread of TB by coughing was a transmission route known by 44.2% of males and 59.6% of females (P < 0.001); 20.0% of participants knew that TB is caused by bacteria; 71.6% of females and 52.3% of males knew TB is infectious (P < 0.001). Regarding approaches to TB prevention, 48.0% of respondents answered patient isolation and 15.2% vaccination. Overall, 50.6% of males and 38.3% of females (P < 0.001) would seek modern medical treatment if hemoptysis occurred. With a persistent cough, 65.4% of respondents would do nothing or wait before consulting a healthcare provider. High numbers of “don’t know” responses were recorded throughout the survey. CONCLUSIONS: Within the population across pilgrimage areas in Saudi Arabia, knowledge is lacking concerning TB transmission, the cause of the disease, means of prevention and the success of treatment, highlighting an urge need for better public education.
Zhang Xuxia, Weicong Ren, Yi Liu, Xuxia Zhang, Chuanyou Li, Zhaogang Sun
Journal of Tuberculosis Research, Volume 01, pp 17-27;

Background: More effective biomarkers for use intuberculosis prevention,diagnosis, and treatmentare urgently needed. The potential of miRNAsfor use as biomarkers of human disease has received much attention; however, suitable miRNA biomarkers for use in tuberculosis (TB) diagnosis and treatment have not yet been identified. Methods: We used human miRNA arrays to identify miRNAs in Peripheral Blood Mononuclear Cells (PBMCs) that are differentially expressed in subjects with active disease, those with latent TB infections (LTBI) and healthy individuals. The relationship between differentially-expressed miRNAs and mRNAs was examined using Tar- getScanS, Pic-Tar and miRanda. The expression profiles of selected miRNAs in subjects with active disease, those with LTBI and healthy individuals were validated by qRT-PCR. Results: miRNA array analysis of PBMCs from subjects with active disease, those with LTBI and healthy individuals identified 26 differentially-expressed miRNAs. Analysis of gene expression levels in THP-1 cells using mRNA arrays identified 87 differentially-expressed genes, 80 of which were up-regulated (ratio >2) and 7 of which were down-regulated (ratio In silico miRNA tar- get prediction identified target mRNAs for 15of the 26 differentially-expressed miRNAs. Diffe- rentially-expressed miRNAs were identified for 90 of the 178 differentially-expressed genes. has-miR-21* and has-miR-26b had the highestnumbers of differentially-expressed target mRNAs.PCR validation of has-miR-21* and has-miR- 15b* demonstrated the fidelity of our microarray results. Conclusion: Whole-genome transcrip- tional profiling identified differentially-express- ed mRNAs and miRNAs. Differentially-express- ed miRNAs combined with predicted differential- ly-expressed mRNAs from the same whole-ge- nome transcriptional profiling may be used as the new ways to better understand TB disease.This discovery of differentially-ex-pressed miRNAsand mRNAs provides a resource for further stu- dies on the role of miRNAs in tuberculosis.
Clara Lema, Kim Dionne, Leo Ayuk, Charles Awasom, Melissa Sander, Carole McArthur, Paul Achu,
Journal of Tuberculosis Research, Volume 01, pp 14-16;

The Paralens? (PL) microscope attachment converts a light microscope into an epi-fluorescencemicroscope. We compared the PL to standard fluorescence microscopy for detection ofMycobacteriain clinical and spiked samples. Overall agreement between the two systems was 100%. Quantitative and qualitative performance was comparable. The PL is an acceptable alternative to standard fluorescence microscopy for detection ofMycobacteria.
Journal of Tuberculosis Research, Volume 01, pp 10-13;

Background: M. tuberculosisis the most important etiological factor of tuberculosis. One of the factors that make TB hard to eradicate is the emergence of M. tuberculosisdrug resistance. Drug resistance in M. tuberculosisis attributed primarily to the accumulation of mutations in the drug target gene. Objectives: to analyze profile of Random Amplified Polymorphic DNA (RAPD) in M. tuberculosisisolates resistant to Isoniazid and found RAPD marker. Methods: seven Isoniazid resistant isolate of M. tuberculosisfrom Ma kassar, Indonesia strain were analyzed by RAPD method using primers OPN 02, OPN 09, OPN 20, BG 65, N 9, that amplification fragment DNA than as molecular marker. Results: The results of the present study showed high degree of polymerphism in theM.tuberculosisstrains in the population, and found that specific DNA fragment at Isoniazid resistant isolates using primer N 9 is 1450 bp as a marker. Conclusion: This study gives information about RAPD marker of M. tuberculosis strain to Isoniazid resistant.
Irene Ane-Anyangwe, Wilfred Fon Mbacham, Henry Dilonga Meriki, Teyim Pride, , Veronique Mbeng Penlap, Leopold Djomkam Tietcheu, , Akindeh Mbuh Nji, Vincent P. K. Titanji
Journal of Tuberculosis Research, Volume 04, pp 72-79;

Drug sensitivity testing to establish resistance to TB drugs takes many months to arrive at. Public health physicians have difficulties with such an approach due to long wait periods and cannot use it to establish community wide prevalence as a way to understand where resistance may be emerging faster and to limit its spread. The objective of this study was to use the dot-blot hybridization technique in the detection of resistance to rifamycin (RIF) and streptomycin (SM) in South- Western Cameroon and to compare the technique with the routine culture and drug susceptibility testing for detecting resistance in a resource poor country, Cameroon. A hospital-based study was conducted at the Regional hospitals of Buea and Limbe and Tiko Central Clinic. Tuberculosis (TB) patients aged 15 to 50 (mean age: 30.50 ± 8.33 standard deviation) were recruited for the study between December 2006 and April 2007. Cultures from 59 patients were tested for rifampicin and streptomycin sensitivity by the modified proportion method and mutational analysis for rpoB codon 516 and rrs codon 513 was performed by the dot-blot hybridization technique. Of the 59 sputum samples collected (36 were males and 23 were females) came from Buea 19 (32.2%), Limbe 20 (33.9%) and Tiko 20 (33.9%) towns respectively. Amplification for the gene showed that there was (59) 100% amplification with primers used for rpoB genes and 43 (72.9%) amplification with primers used for the rrs gene. Mutational analysis demonstrated that resistance to RIF was common in females (52.1%) than males (41.7%) while 6% of the samples were indeterminate. 12 (20.3%) samples showed phenotypic and genotypic resistance to RIF compared to 34 samples (58.1%) for SM. Phenotypic resistance and genotypic susceptibility were found in 5 (8.5%) RIF and 3 (4.7%) SM compared to phenotypic susceptibility and genotypic resistance that were found in 2 (3.5%) RIF and 3(4.7%) SM. Double mutation on rpoB and rrs genes occurred in 8 (13.6%) DNA samples. Resistance to RIF and SM due to mutations on the rpoB and rrs genes respectively in the SW region was found to be high and comparable to the drug susceptibility testing by 92%, (95% CI: 75.7 - 99.1). The Dot-blot technique will be useful in rapidly assessing the effectiveness of national TB control programs in limiting the spread of resistance strains in Cameroon.
Soma Chakraborty, Arindam Chakraborty, Tathagata Talukder, Mita Mukherjee, Tridip Chatterjee
Journal of Tuberculosis Research, Volume 04, pp 61-71;

Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than in any other country. Anti-tubercular drugs (ATDs) have been used for decades, and widespread resistance to them is a very serious public health concern in any part of the world. Aim of this study was to determine the prevalence of Rifampicin (the first line Anti-TB drug) resistance among both pulmonary and extra-pulmonary samples tested positive for Mycobacterium tuberculosis and thereby predict the prevalence of Multi-drug resistant (MDR) tuberculosis in Kolkata and its Suburban regions. All 331 randomly collected clinical samples (both Pulmonary and Extra Pulmonary) were initially screened by Zeihl-Neelsen AFB staining followed by culture on BacT/Alert 3D system and on Lowenstein-Jensen medium and the positive samples were subjected to detection of Mycobacterium tuberculosis complex (MTBC) and simultaneous analysis of Rifampicin resistance by Xpert MTB/RIF assay. Out of the 51 (15.40%) culture positive samples, 13.7% of pulmonary samples and 9.09% of extra-pulmonary samples were Rifampicin resistant. The prevalence of Rifampicin resistant TB in our study is high and the possible reasons can be mixing of new as well as retreatment cases and smaller sample size but, yet it can help Government and public health regulatory bodies to formulate adequate strategies to fight against drug resistant tuberculosis, especially in this part of the world.
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