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Comparison of cost-effectiveness between the quantiFERON-TB Gold-In-Tube and T-Spot tests for screening health-care workers for latent tuberculosis infection
Shigeto Mukai, Katsumi Shigemura, Fukashi Yamamichi, Koichi Kitagawa, Nozomi Takami, Masashi Nomi, Soichi Arakawa, Masato Fujisawa
January-March 2017, 6(1):83-86
DOI:10.4103/2212-5531.201899  PMID:28317810
Objective/Background: There are several methods used to screen for latent tuberculosis (TB) infection (LTBI) including the QuantiFERON-TB Gold-in-Tube (QFT-GIT) and T-SPOT-TB (T-SPOT) tests. Many studies have reported the equivalence of these two methods, but it is unclear which of them is more cost effective. We investigated the age and cost issues of these tests in screening for LTBI among health-care workers. Materials and Methods: One hundred and forty new employees during 2008–2011 in our hospital were screened using the QFT-GIT test, and 140 new employees during 2011–2014 were screened with the T-SPOT test for LTBI. The results of both tests were classified as positive, undetermined (retesting required), or negative. Results: There were six positive results (4.29%), eight undetermined results (5.71%), and 126 negative results (90.0%) with the QFT-GIT test. As for the T-SPOT test, there were eight positive results (5.71%), three undetermined results (2.14%), and 129 negative results (92.1%). Fourteen LTBI employees (6 in QFT-GIT and 8 in T-SPOT) were detected statistically equally using the two methods (P = 0.79). The total costs, including those incurred for retesting, were $7,711.86 (US dollar) and $6,525.42 for the QFT-GIT and T-SPOT tests (cost of one test is $55.08 for QFT-GIT and $46.61 for T-SPOT), respectively. Conclusion: T-SPOT is one of the options for screening for LTBI partly owing to the viewpoint of cost-effectiveness. Further prospective studies need to be considered for a definitive conclusion.
  3,348 500 -
Role of Vitamins B, C, and D in the fight against tuberculosis
Gaurav Tyagi, Pooja Singh, Mandira Varma-Basil, Mridula Bose
October-December 2017, 6(4):328-332
DOI:10.4103/ijmy.ijmy_80_17  PMID:29171444
Worldwide, tuberculosis (TB) is still a serious and significant health concern, more so with the emergence of multidrug-resistant-TB. The inability of mankind to control this infection stems from the fact that the vaccines and drugs that were once effective against TB are no longer efficacious. This has led to a search for new antituberculous agents and adjuvant therapy. Vitamins are being revisited for their role in pathogenicity as well as for their antimycobacterial properties. Vitamins such as biotin and thiamin are essential for Mycobacterium tuberculosis and are required for establishment of infection. On the other hand, vitamins such as Vitamin C and Vitamin D have been shown to possess antimycobacterial properties. To combat M. tuberculosis, innovative strategies need to be devised, keeping in mind the efficacy of the agent to be used. Vitamins can prove to be useful agents capable of modifying the life cycle and biology of M. tuberculosis. We present here a brief overview of the available knowledge on thiamin, biotin, Vitamin C, and Vitamin D, keeping TB treatment and control in perspective.
  2,373 610 3
Patients at high risk of tuberculosis recurrence
Mehdi Mirsaeidi, Ruxana T Sadikot
January-March 2018, 7(1):1-6
DOI:10.4103/ijmy.ijmy_164_17  PMID:29516879
Recurrent tuberculosis (TB) continues to be a significant problem and is an important indicator of the effectiveness of TB control. Recurrence can occur by relapse or exogenous reinfection. Recurrence of TB is still a major problem in high-burden countries, where there is lack of resources and no special attention is being given to this issue. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 47%. This variability is related to differences in regional epidemiology of recurrence and differences in the definitions used by the TB control programs. In addition to treatment failure from noncompliance, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include gender differences, malnutrition; comorbidities such as diabetes, renal failure, and systemic diseases, especially immunosuppressive states such as human immunodeficiency virus; substance abuse; and environmental exposures such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being identified. Information on temporal and geographical trends of TB cases as well as studies with whole-genome sequencing might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and an understanding of host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.
  2,339 542 2
Challenges beyond elimination in leprosy
Farah Naaz, Partha Sarathi Mohanty, Avi Kumar Bansal, Dilip Kumar, Umesh Datta Gupta
July-September 2017, 6(3):222-228
Every year >200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. The World Health Organization has set a target to interrupt the transmission of leprosy globally by 2020. It is important, in terms of global action and research activities, to consider the eventuality of multidrug therapy (MDT) resistance developing. It is necessary to measure disease burden comprehensively, and contact-centered preventive interventions should be part of a global elimination strategy. Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. MDT has proven to be a powerful tool in the control of leprosy, especially when patients report early and start prompt treatment. Adherence to and its successful completion is equally important. This paper has reviewed the current state of leprosy worldwide and discussed the challenges and also emphasizes the challenge beyond the elimination in leprosy.
  2,316 532 1
Fighting tuberculosis by drugs targeting nonreplicating Mycobacterium tuberculosis bacilli
Angelo Iacobino, Giovanni Piccaro, Federico Giannoni, Alessandro Mustazzolu, Lanfranco Fattorini
July-September 2017, 6(3):213-221
Current tuberculosis (TB) treatment requires 6 months of combination therapy with isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol for active TB and 9 months of INH or 3 months of rifapentine (RFP) + INH for latent TB. The lungs of patients with active and latent TB contain heterogeneous mixtures of cellular and caseous granulomas harboring Mycobacterium tuberculosis bacilli ranging from actively replicating (AR) to nonreplicating (NR), phenotypically drug-resistant stages. Several in vitro models to obtain NR cells were reported, including exposure to hypoxia, nutrient starvation, acid + nitric oxide, and stationary phase. Overall, these models showed that RIF, RFP, PA-824 (PA), metronidazole (MZ), bedaquiline (BQ), and fluoroquinolones were the most active drugs against NR M. tuberculosis. In hypoxia at pH 5.8, some combinations killed AR plus NR cells, as shown by lack of regrowth in liquid media, whereas in hypoxia at pH 7.3 (the pH of the caseum), only RIF and RFP efficiently killed NR bacilli while several other drugs showed little effect. In conventional mouse models, combinations containing RFP, BQ, PA, PZA, moxifloxacin, sutezolid, linezolid, and clofazimine sterilized animals in ≤2 months, as shown by lack of viable bacilli in lung homogenates after 3 months without therapy. Drugs were less effective in C3HeB/FeJ mice forming caseous granulomas. Overall, in vitro observations and in vivo studies suggest that the search for new TB drugs could be addressed to low lipophilic molecules (e.g., new rpoB inhibitors with clogP < 3) killing NR M. tuberculosis in hypoxia at neutral pH and reaching high rates of unbound drug in the caseum.
  1,989 571 2
Performance of the Xpert MTB/RIF assay in the diagnosis of tuberculosis in formalin-fixed, paraffin-embedded tissues
Pascal Polepole, Mwila Kabwe, Mpanga Kasonde, John Tembo, Aaron Shibemba, Justin O'Grady, Nathan Kapata, Alimuddin Zumla, Matthew Bates
January-March 2017, 6(1):87-93
DOI:10.4103/2212-5531.201892  PMID:28317811
Objective/Background: Extrapulmonary tuberculosis (EPTB), which accounts for 10%–40% of the global burden of TB, with the highest incidence in Sub-Saharan Africa, is strongly associated with human immunodeficiency virus infection. Diagnosing EPTB is challenging, and recently, there has been a concerted effort to evaluate the latest molecular diagnostics for diagnosing TB in a range of specimen types. The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is one such technology, which simultaneously detects Mycobacterium tuberculosis and rifampicin resistance. Our objective was to evaluate the accuracy of the Xpert MTB/RIF assay for the diagnosis of EPTB and detection of rifampicin resistance in routinely processed formalin-fixed, paraffin-embedded (FFPE) tissues, compared with histological detection of TB as the gold standard. Methods: A convenience set of 100 biobanked FFPE tissues, including lymph nodes (n = 64), male genital tract tissue (n = 10), abdominal tissue (n = 8), female genital tissue (n = 5), breast tissue (n = 5), synovial tissue (n = 4), skin (n = 2), tongue tissue (n = 1), and thyroid (n = 1), from routine cases of clinically suspected EPTB admitted to the University Teaching Hospital, Lusaka, Zambia, were analyzed using the Xpert MTB/RIF assay and in-house polymerase chain reaction (PCR) assay targeting IS6110, in parallel with Ziehl–Neelsen (ZN) staining, against histology as the gold standard. Results: Some 66% of specimens had histological evidence of TB infection. ZN staining was positive for TB in 8% of cases, and Xpert MTB/RIF was positive for TB in 25% of cases. Taking histology as the gold standard, the sensitivity and specificity were as follows: In lymph tissue the accuracy of the Xpert MTB/RIF assay was 41% (95%CI 27-57), not significantly better than ZN or the in-house PCR assay. In non-lymph tissue the sensitivity of the in-house PCR assay was 82% (95%CI: 56%-95%), significantly higher than the Xpert MTB/RIF assay (P = 0.004). The Xpert MTB/RIF assay indicated rifampicin resistance in just three cases. Conclusion: The Xpert MTB/RIF assay is potentially a useful tool for the diagnosis of TB in routine FFPE tissues.
  1,945 499 3
Nontuberculous mycobacterial species and Mycobacterium tuberculosis complex coinfection in patients with pulmonary tuberculosis in Dr. Soetomo Hospital, Surabaya, Indonesia
Ni Made Mertaniasih, Deby Kusumaningrum, Eko Budi Koendhori, Soedarsono , Tutik Kusmiati, Desak Nyoman Surya Suameitria Dewi
January-March 2017, 6(1):9-13
DOI:10.4103/2212-5531.201894  PMID:28317798
Objective/Background: The aim of this study was to analyze the detection of nontuberculous mycobacterial (NTM) species derived from sputum specimens of pulmonary tuberculosis (TB) suspects. Increasing prevalence and incidence of pulmonary infection by NTM species have widely been reported in several countries with geographical variation. Materials and Methods: Between January 2014 and September 2015, sputum specimens from chronic pulmonary TB suspect patients were analyzed. Laboratory examination of mycobacteria was conducted in the TB laboratory, Department of Clinical Microbiology, Dr. Soetomo Hospital, Surabaya. Detection and identification of mycobacteria were performed by the standard culture method using the BACTEC MGIT 960 system (BD) and Lowenstein–Jensen medium. Identification of positive Mycobacterium tuberculosis complex (MTBC) was based on positive acid-fast bacilli microscopic smear, positive niacin accumulation, and positive TB Ag MPT 64 test results (SD Bioline). If the growth of positive cultures and acid-fast bacilli microscopic smear was positive, but niacin accumulation and TB Ag MPT 64 (SD Bioline) results were negative, then the isolates were categorized as NTM species. MTBC isolates were also tested for their sensitivity toward first-line anti-TB drugs, using isoniazid, rifampin, ethambutol, and streptomycin. Results: From 2440 sputum specimens of pulmonary TB suspect patients, 459 isolates (18.81%) were detected as MTBC and 141 (5.78%) as NTM species. Conclusion: From the analyzed sputum specimens, 18.81% were detected as MTBC and 5.78% as NTM species. Each pulmonary TB suspect patient needed clinical settings to suspect causative agents of MTBC and/or NTM species; clinicians have to understand the local epidemiological data for the evaluation of causes of lung infection to determine appropriate therapy.
  1,752 410 2
Extrapulmonary tuberculosis in colombian children: Epidemiological and clinical data in a reference hospital
Eileen Viviana Fonseca Sepulveda, Luisa Fernanda Imbachí Yunda, Kelly Christina Márquez Herrera, German Camacho Moreno
April-June 2017, 6(2):132-137
DOI:10.4103/ijmy.ijmy_65_17  PMID:28559513
Background: The pediatric population is at increased risk of disseminated and extrapulmonary tuberculosis (TB). There is little information on children affected by this entity. The demographic, clinical, and outcome characteristics of the treatment of children with extrapulmonary TB, treated at a national reference institution between January 1, 2008, and December 31, 2016, are described and analyzed in this work. Materials and Methods: This was a retrospective observational study. Cases of extrapulmonary TB were identified, and variables were collected based on each criterion used for diagnosis and treatment outcomes. A descriptive analysis of the variables collected was performed. Results: Ninety-three cases were identified, of which 32 (34.4%) met the criteria for extrapulmonary TB. The mean age was 10.2 years (range 0.8–17 years), and the most frequent site of extrapulmonary TB was lymph node 40.6%, meningeal 21.9%, and ocular 18.8%. Bacteriological confirmation was obtained in 8 cases (25%) while the remaining 24 cases (75%) were classified as cases of clinically diagnosed TB. Two patients (6.2%) died during treatment although their decease was not attributable to TB. Conclusion: The clinical criterion was fundamental to establish the diagnosis. The microbiological isolation rate was low. Molecular biology tools increase bacteriological performance although their extended use is limited by cost. Regional multicenter studies are required to identify the target population and the tools necessary for timely management and treatment.
  1,690 399 -
Rapid laboratory diagnosis of pulmonary tuberculosis
Prasanna Bhirud, Ameeta Joshi, Nilma Hirani, Abhay Chowdhary
July-September 2017, 6(3):296-301
Background: Tuberculosis (TB) ranks as the second leading cause of death from an infectious disease worldwide. Early diagnosis of Mycobacterium tuberculosis in clinical samples becomes important in the control of TB both for the treatment of patients and for curbing of disease transmission to the others in the community. The study objective was to perform Ziehl–Neelsen (ZN) staining, fluorochrome staining, line probe assay (LPA), and loop-mediated isothermal amplification (LAMP) assay for rapid detection of pulmonary TB (PTB) and to compare the results of LPA and LAMP in terms of sensitivity, specificity, and turnaround time. Methods: A total of 891 sputum samples from clinically diagnosed/suspected cases of TB were subjected to ZN and fluorochrome staining. Smear positive samples were subjected to LPA, and smear negative were cultured on Lowenstein–Jensen media. A total of 177 samples were subjected to liquid culture and LAMP. Conventional culture was considered as “gold standard” for calculation of parameters. Results: Light-emitting diode fluorescence microscopy had the same sensitivity as ZN with similar high specificity. LPA was performed on 548 sputum samples which includes 520 smear positive and 28 smear negative culture positive samples and multidrug-resistant TB was detected in 32.64%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TB-LAMP on direct sputum samples was found to be 98.96%, 95%, 96%, and 98.70%, respectively, when compared with ZN smear microscopy. By considering culture as “gold standard,” LAMP showed a sensitivity, specificity, PPV, and NPV of 98.94%, 96.34%, 96.90%, and 98.75%, respectively. The sensitivity and PPV of TB-LAMP were 98.97% and 96%, respectively, when compared with LPA. Conclusions: A successful rapid laboratory diagnosis of PTB is possible when one combines the available methodology of microscopy, culture as well as molecular techniques. The LAMP assay was found to be simple, self-contained, and efficacious for early diagnosis of suspected cases of PTB with advantages of having a high throughput, no requirements of sophisticated equipment, and complex biosafety facilities.
  1,646 439 4
Pulmonary tuberculosis in a Pediatric Reference Hospital in Bogotá, Colombia
Luisa Fernanda Imbachí Yunda, Eileen Viviana Fonseca Sepúlveda, Kelly Christina Márquez Herrera, Germán Camacho Moreno
July-September 2017, 6(3):258-263
Background: In Colombia, epidemiological and clinical information related to pediatric tuberculosis (TB) is scarce. Data are needed to define the impact of the disease and to strengthen measures for detection and treatment. It is proposed to analyze the pediatric population diagnosed with pulmonary TB in a national reference institution. Methods: Retrospective observational study including pediatric patients with pulmonary and miliary TB, and pulmonary and extrapulmonary involvement, treated between January 1, 2008 and December 31, 2016. A descriptive analysis of the selected variables was done. Results: A total of 93 cases of diagnosed TB were identified, of which 61 cases were classified as pulmonary (65.6%). The location of TB occurred only in lungs in 51 patients (83.6%), was miliar in 3 (4.9%), pulmonary and extrapulmonary involvement in 7 patients (11.5%). The mean age was 7.5 years (0.5–18 years). Clinical criteria used for diagnosis was related to 98.3% of the cases, whereas radiological criteria in 90.2%. Bacteriological criterion was met in 42.6% of the cases. The most frequent symptoms were coughing (83.6%), fever (63.9%), and weight loss (26.2%); human immunodeficiency virus co-infection occurred in 3 cases (4.9%). During treatment, 5 mortality cases were recorded, although they were not attributable to TB. Conclusions: The epidemiological characterization of pediatric patients with pulmonary TB helps to achieve a better diagnostic approach in this population. Improving monitoring and follow-up activities in children with pulmonary TB, as well as promoting actions for adequate prevention and treatment is highly necessary.
  1,755 278 -
Epidemiology of extrapulmonary and disseminated tuberculosis in a tertiary care center in Oman
Zied Gaifer
April-June 2017, 6(2):162-166
DOI:10.4103/ijmy.ijmy_31_17  PMID:28559518
Background: The incidence of extrapulmonary and disseminated tuberculosis (TB) cases is increasing worldwide, and this growth significantly impacts TB-related morbidity and mortality. Little is known about the host risk factors for extrapulmonary and disseminated TB. In this study, we examined those risk factors. Materials and Methods: We conducted a retrospective review of all TB cases admitted to Sultan Qaboos University Hospital from 2006 to 2015. We compared extrapulmonary TB (EPTB) cases with pulmonary and disseminated TB cases. We evaluated the risk factors associated with the development of extrapulmonary and disseminated TB using logistic regression analysis. Results: We reviewed 260 TB cases, of which EPTB comprised 37%, PTB comprised 53%, and disseminated TB comprised 10%. The most common sites of infection in the EPTB group were the lymph nodes and the abdomen. Disseminated TB and TB meningitis were more common in expatriates than in Omanis. Patients with EPTB were less likely to smoke compared to a patient with PTB. Patients with disseminated TB had a higher mortality when compared to patients with EPTB (adjusted odds ratio [OR], 0.004; 95% confidence intervals [CI]: 0.001–0.054;P = 0.001) and PTB (adjusted OR, 0.022; 95% CI: 0.004–0.115;P = 0.001). Human immunodeficiency virus (HIV) was the main risk factor for patients with disseminated TB when compared to patients with extrapulmonary and PTB. Conclusion: The rates of extrapulmonary and disseminated TB in Oman are higher than what has been recognized. Expatriates, patients with HIV, and smokers are at high risk for disseminated TB. In these patients, suspected extrapulmonary sites should be evaluated and sampled to exclude disseminated TB.
  1,659 340 1
Port-site infections by nontuberculous mycobacterium: A retrospective clinico-microbiological study
Roumi Ghosh, Soumen Das, Asmita De, Harish Kela, Makhan Lal Saha, Prasanta Kumar Maiti
January-March 2017, 6(1):34-37
DOI:10.4103/2212-5531.201901  PMID:28317802
Background: Port-site infection (PSI) is a prevailing, chronic, nagging, treatment refractory complication of laparoscopic surgery (LS). It neutralizes the advantages of minimally invasive surgery and increases morbidity, treatment cost of patient, leading to loss of confidence on operating surgeon. PSIs are preventable with appropriate preoperative, intraoperative, and postoperative measures. Atypical mycobacterium is most commonly associated with nonhealing postlaparoscopic wound infections, causing outbreaks or sporadic cases worldwide. Purpose: We retrospectively studied the occurrence of nontuberculous mycobacterium (NTM) from PSIs following LS that did not respond to antibiotics used for pyogenic infections and having sterile routine aerobic cultures and their antimicrobial susceptibility pattern to guide proper management. Methods: The study was done in a tertiary care hospital of Eastern India over a 1-year period which included PSI cases with delayed onset not responding to antibiotics, following different types of LS. Pus/discharge from 32 patients was collected and examined for isolation and identification of the causative agents. Gram stain and Ziehl–Neelsen staining methods were used for direct examination. Culture media included blood agar, Robertson's cooked meat broth, MacConkey agar, and Lowenstein–Jensen medium. Isolates from the cases were identified using biochemical tests or molecular methods and studied the antimicrobial susceptibility pattern by the standard microbiologic procedures. Results: Mycobacterium abscessus (13) and Mycobacterium fortuitum (2) were isolated from 15 serosanguinous drainage obtained from 32 cases by routine microbiological techniques. All isolates analyzed for antimicrobial susceptibility pattern were highly sensitive to clarithromycin (93.3%), amikacin (93.3%), and imipenem (80%) but were variable to ciprofloxacin, ofloxacin, and linezolid. Conclusions: Our present study shows frequent association of NTM with laparoscopic port-site nonhealing chronic infection or wound dehiscence. Although direct microscopy can give us a clue to diagnosis, culture isolation is required for speciation and antimicrobial susceptibility testing, which helps formulate therapeutic regimen.
  1,687 289 3
Association between pulmonary tuberculosis and Type 2 diabetes in Sudanese patients
Mona Ahmed, Ibtihal Omer, Sannaa M. A Osman, Eltayib H Ahmed-Abakur
January-March 2017, 6(1):97-101
DOI:10.4103/ijmy.ijmy_13_17  PMID:28317813
Introduction: Tuberculosis (TB) and diabetes mellitus (DM) are both important health issues, and the association between DM and TB may be the next challenge for global TB control worldwide, type 2 DM (T2DM) responsible for 90% of DM cases. Persons with diabetes have a significantly increased risk of active TB, which is two to three times higher than in persons without diabetes. The aim of this study was to determine the association between pulmonary tuberculosis (PTB) and T2DM among Sudanese patients and also to determine the association between hemoglobin A1c (HbA1c) percentage in diabetic patients and development of PTB and effect of duration of T2DM in developing PTB. Materials and Methods: A total of 120 sputum samples were collected from patients during 6 months in Ribat University Hospital, Khartoum, Sudan. Sixty of them were known type 2 diabetic patients categorized as study group and sixty were nondiabetic patients categorized as control group. Ziehl–Neelsen smear preparation and DNA were extracted from sputum for detection of Mycobacterium tuberculosis by polymerase chain reaction (PCR). Results: Among the 120 sputum specimens, 72 (60%) were males and 48 (40%) were females. Fourteen (19.4%) males and 6 (12.5%) females had PTB, the difference was not statistically significant according to gender P = 0.229. According to treatment modalities, diabetic patients were treated with injectable insulin (36.7%), PCR positive was 4(33.3%) P value (0.853), oral hypoglycemic drugs (51.7%) PCR positive 7 (58.3%) P value (0.849) and dietary control (11.7%) PCR positive (1 (8.3%) P value (1.000) Were insignificant differences. The frequency of HbA1c of 58 patients with diabetes was 24 (41.4%) who had controlled DM (HbA1c level ≤ 6.5%) and 34 (58.6%) had uncontrolled DM. Of the 60 patients with diabetes, 12 had PTB with uncontrolled DM, with significant difference (P=0.000). The mean duration of diabetes mellitus was (6.92 years ± Std 6.801) and the frequency of diabetes mellitus in first 10 years was 47 (78.3%), in (11-20) years was 10 (16.7%) and in (21-30) years was 3 (5%), the PCR positive PTB showed 10(21.3%) for the first 10 years, (11-20) years was 2 (20%) and zero (0.0%) for (21-30) years, P-value (0.480) insignificant different. Conclusions: In summary, we found consistent evidence for an increased risk of TB among patients with uncontrolled DM (high-level HbA1c).
  1,587 358 -
Contribution of putative efflux pump genes to isoniazid resistance in clinical isolates of Mycobacterium tuberculosis
Anshika Narang, Astha Giri, Shraddha Gupta, Kushal Garima, Mridula Bose, Mandira Varma-Basil
April-June 2017, 6(2):177-183
DOI:10.4103/ijmy.ijmy_26_17  PMID:28559521
Background: Isoniazid (INH) resistance in Mycobacterium tuberculosis has been mainly attributed to mutations in katG (64%) and inhA (19%). However, 20%–30% resistance to INH cannot be explained by mutations alone. Hence, other mechanisms besides mutations may play a significant role in providing drug resistance. Here, we explored the role of 24 putative efflux pump genes conferring INH-resistance in M. tuberculosis. Materials and Methods: Real-time expression profiling of the efflux pump genes was performed in five INH-susceptible and six high-level INH-resistant clinical isolates of M. tuberculosis exposed to the drug. Isolates were also analyzed for mutations in katG and inhA. Results: Four high-level INH-resistant isolates (minimum inhibitory concentration [MIC] ≥2.5 mg/L) with mutations at codon 315 (AGC-ACC) of katG showed upregulation of one of the efflux genes Rv1634, Rv0849, efpA, or p55. Another high-level INH-resistant isolate (MIC 1.5 mg/L), with no mutations at katG or inhA overexpressed 8/24 efflux genes, namely, Rv1273c, Rv0194, Rv1634, Rv1250, Rv3823c, Rv0507, jefA, and p55. Five of these, namely, Rv0194, Rv1634, Rv1250, Rv0507, and p55 were induced only in resistant isolates. Conclusion: The high number of efflux genes overexpressed in an INH-resistant isolate with no known INH resistance associated mutations, suggests a role for efflux pumps in resistance to this antituberculous agent, with the role of Rv0194 and Rv0507 in INH resistance being reported for the first time.
  1,522 393 4
An evaluation of innovative community-based approaches and systematic tuberculosis screening to improve tuberculosis case detection in Ebonyi State, Nigeria
Daniel C Oshi, Joachim C Omeje, Sarah N Oshi, Isaac N Alobu, Ngozi E Chukwu, Chukwuemeka Nwokocha, Obiageli F Emelumadu, Chidubem L Ogbudebe, Anthony O Meka, Kingsley N Ukwaja
July-September 2017, 6(3):246-252
Background: National tuberculosis (TB) programmes globally rely heavily on passive case finding for detecting TB in the community as advocated by the World Health Organization (WHO). TB case detection is low in Nigeria despite improvement in TB services and coverage. Methods: A retrospective evaluation of an active case-finding intervention utilizing community-based approaches and targeted systematic TB screening in Ebonyi State, Nigeria was done. The analysis was performed using Epi Info. Results: Using community-based and health-facility-based systematic screening strategies, 218,751 persons were screened, with 19.7% of them being presumptive TB cases. Among these, 23,729 (55.1%) submitted sputum samples for microscopy, and 764 (3.2%) had smear-positive TB. In addition, 683 individuals were diagnosed with other forms of TB using X-ray and clinical evaluation giving a total of 1447 all forms of TB cases. The overall number needed to screen (NNS) to find one person with all forms of TB through the project was 151. The NNS was 53 for general outpatients, 88 through contact tracing, and 110 among HIV-infected persons. Conclusions: Active case-finding strategies achieved good yields though early loss to follow-up was high. Active case finding is recommended for integration into national TB control policy and practice.
  1,549 295 -
Nontuberculous mycobacteria pathogenesis and biofilm assembly
Sara Sousa, Maria Bandeira, Patricia Almeida Carvalho, Aida Duarte, Luisa Jordao
January-March 2015, 4(1):36-43
Nontuberculous mycobacteria (NTM) are emergent pathogens whose importance in human health has been gaining relevance after being recognized as etiological agents of opportunist infections in HIV patients. Currently, NTM are recognized as etiological agents of several respiratory and extra-respiratory infections of immune-competent individuals. The environmental nature of NTM together with the ability to assemble biofilms on different surfaces plays a key role on their pathogenesis. In the present work the ability of three fast-growing NTM (Mycobacterium smegmatis, Mycobacterium fortuitum and Mycobacterium chelonae) to persist within a model of human alveolar macrophages was evaluated. Most often human infections with NTM occur by contact with the environment. Biofilms can work as environmental reservoirs. For this reason, it was decided to evaluate the ability of NTM to assemble biofilms on different surfaces. Scanning electron microscopy was used to elucidate the biofilm structure. The ability to assemble biofilms was connected with the ability to spread on solid media known as sliding. Biofilm assembly and intracellular persistence seems to be ruled by different mechanisms.
  1,665 156 14
Analysis of a novel multiplex polymerase chain reaction assay as a sensitive tool for the diagnosis of indeterminate and tuberculoid forms of leprosy
V Sundeep Chaitanya, Luz Cuello, Madhusmita Das, A Sudharsan, Pavithrra Ganesan, K Kanmani, Lakshmi Rajan, Mannam Ebenezer
January-March 2017, 6(1):1-8
DOI:10.4103/2212-5531.201885  PMID:28317797
Objective/Background: Clinical diagnosis of indeterminate and tuberculoid leprosy is often difficult due to limited and confounding signs and symptoms. In the current study, we evaluated the utility of new multiplex polymerase chain reaction (PCR) using Mycobacterium leprae-specific DNA sequences in the pseudogene regions of ML1545, ML2180, and ML2179 for PCR-based diagnosis of indeterminate leprosy (IND) and leprosy cases across the immunological spectrum. The sensitivity was compared with that of RLEP PCR. Methods: DNA was extracted from paraffin-embedded skin biopsy specimens of 220 leprosy cases, which were divided into IND (41), tuberculoid form (3), borderline tuberculoid (42), midborderline (3), borderline lepromatous (n=59), and lepromatous leprosy (72) cases. PCR positivity of both multiplex and RLEP PCR were compared in all the samples. A decision tree was constructed using the classification and regression trees algorithm to predict the probability of PCR positivity with the new multiplex PCR scheme in various clinical groups of leprosy. Sensitivity of each pseudogene target was determined using real-time PCR assays, and specificity was confirmed by PCR amplification of DNA extracted from three other mycobacterial species and skin biopsies of 44 non-leprosy cases. Results: A multiplex PCR positivity of 75.61% was noted in IND cases when compared to that of 58.54% using RLEP PCR (P < 0.05). Enhanced multiplex PCR positivity was noted across various clinical groups in comparison to RLEP PCR. The decision tree classifier has predicted statistically significant probability for multiplex PCR positivity among RLEP-PCR negative group and clinical groups with a low bacillary load. Conclusion: This new multiplex PCR scheme can support the diagnosis of indeterminate and tuberculoid forms of leprosy with limited clinical manifestations and can be implemented in basic clinical/diagnostic setting that possess conventional PCR facilities.
  1,488 333 -
Epidemiological and laboratorial profile of patients with isolation of nontuberculous mycobacteria
Heloisa Silveira Paro Pedro, Andréa Gobetti Vieira Coelho, Isabela Mazuco Mansur, Ana Carolina Chiou, Maria Izabel Ferreira Pereira, Naiara Cristina Ule Belotti, Manuela Galloy Sanches Ismael, Maria Rita de Cássia Oliveira Cury, Susilene Maria Tonelli Nardi, Érica Chimara
July-September 2017, 6(3):239-245
Background: An increase in NTM diseases in the international scenario has been observed in recent years. Aims: To analyze the epidemiological and laboratory profiles of patients with isolation of nontuberculous mycobacteria (NTM) over one decade. A retrospective analysis of records of a mycobacterial reference laboratory found 135 cases with isolation of NTM. Methods: Clinical and epidemiological data were collected from the records of government health clinics and from the State notification system (TBWEB). The cases were geocoded by location based on the street address in the Mercator Transverse Universal projection, Datum SAD/69 and MapInfo software. Results: Most patients were male (66.7%), older than 50 years (40%) and had only completed elementary schooling (38.5%). Associated health problems were found in 71.8% of the subjects, with 43.7% being HIV positive and 25.9% having had tuberculosis in the past. Hospitals were the most able institutions to diagnose cases (45.2%). Sputum was the most common material tested (63.0%) with the bacilloscopy being positive in 33.3% of cases. The most common mycobacteria species in the region were Mycobacterium avium and M. abscessus/M. massiliense/M. bolletii. When the regional reference municipality was analyzed, M. avium and M. fortuitum were the most common species isolated in the urban area. Conclusions: In the study region, mycobacteriosis most affected adult males with low schooling. Most patients presented comorbidities in particular co-infection with the HIV virus. M. avium is the most prevalent species in the region with the M. abscessus/M. massiliense/M. bolletii species being the main cause of nosocomial infections.
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Are WHO approved nucleic acid amplification tests causing large-scale “false identification” of rifampicin-resistant tuberculosis?: Programmatic experience from south india
Praveen Sanker, Anusree P Ambika, Vishnu T Santhosh, Ramya Puthukkudi Kottuthodi, Ravikrishnan Balakrishnan, Sunil Kumar Mrithunjayan, Hisham Moosan
January-March 2017, 6(1):21-26
DOI:10.4103/2212-5531.201900  PMID:28317800
Introduction: The nucleic acid amplification tests (NAATs): Line probe assay and GeneXpert (Xpert) have evolved as the primary tool for identification of rifampicin (RIF)-resistant (RR) tuberculosis (TB) worldwide, primarily because of the ease and speed. We rechecked RR isolates identified by NAATs from presumptive RR TB cases belonging to South India by the Revised National TB Control Program, India using multiple RIF concentrations on Bactec MGIT system and compared the mutation patterns with the resistance levels. Methodology: Standard protocol for Bactec MGIT system as given by the manufacturer modified for the multiple RIF concentrations was used. All the retests were done in a certified BSL3 laboratory. Results: We found that there is a mismatch of up to 20% (RIF breakpoint 0.5 mg/L); the NAATs probably overidentifying RR TB. Half of the cases with mismatch showed a sub-breakpoint rise in resistance level (0.125 mg/L to 0.5 mg/L RIF). Discussion and Conclusion: The probable reasons for the mismatch are “sub-breakpoint low-level resistance mutants,” hetero-resistant bacterial populations, and other inherent test limitations along with the low RR TB prevalence in South India (<5%) among “presumptive multidrug-resistants.” This could be due to the incomplete selection pressure by an inadequate RIF exposure caused by various factors including a low-RIF dosage being used widely and poor Directly observed treatment. To prevent the false diagnosis of RR TB in a massive scale when using NAATs, we may need to enforce a carefully targeted testing approach and a phenotypic susceptibility testing with multiple RIF concentrations for confirmatory purposes.
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Knowledge on tuberculosis among the members of a rural community in Myanmar
Kyaw San Lin, Chit Sandy Kyaw, Ye Pyae Sone, Su Yi Win
July-September 2017, 6(3):274-280
Background: Myanmar, one of the high tuberculosis (TB) burden countries, is in serious need of research work to develop strategies aiming to tackle the problem. Conducting a study on the knowledge of the population will help understand the flaws in the National TB Control Program (NTP), and how to correct them, and further strategic planning to reach the goals of Sustainable Development Goals. Aims: The aim of the study was to access sociodemographic characteristics, knowledge, and behavioral practice of TB among the community members in Ngar Syu Taung Village, Hlegu Township. This is a cross-sectional descriptive study. The number of defined person was 200. Methods: Nonprobability convenience sampling method was used. Data collection method used was face-to-face interviewing method using questionnaires. They were collected by house officers as a part of the community medicine training program. Results: Less than half of the respondents were not aware of TB meningitis (41%) and TB osteomyelitis (49%) and they are not aware that diabetic patients are one of the commonly infected people (41.5%). Furthermore, less than one-third of the patients know that TB can infect the gut (23%) and cause bowel obstruction (30.5%). Conclusions: Wrong ideas should be tackled, and lacking knowledge should be enlightened. Nationwide studies using stronger study designs are also urgently needed. Implementing these evidence into NTP is necessary for Myanmar, to escape from being a TB high-burden country.
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Utility of QuantiFERON tuberculosis gold-in-tube test for detecting latent tuberculosis infection among close household contacts of confirmed tuberculosis patients in Accra, Ghana
Gloria Ivy Mensah, Sandra Akoley Sowah, Nana Yaw Asare Yeboah, Kennedy Kwasi Addo, Dolly Jackson-Sillah
January-March 2017, 6(1):27-33
DOI:10.4103/2212-5531.201891  PMID:28317801
Objective/Background: Introduction of the interferon gamma (IFN-γ) release assays with their higher sensitivity and specificity over the traditional tuberculin skin test has improved testing for latent tuberculosis infection (LTBI). None of the IFN-γ release assays has ever been used to screen for LTBI in Ghana. This study set out to determine the utility of the QuantiFERON TB Gold-in-Tube (QFT-GIT) test for the diagnosis of LTBI among close household contacts of newly diagnosed sputum smear-positive tuberculosis (TB) patents in Accra, Ghana, and the associated risk factors for a positive QFT-GIT test. Materials and Methods: Close household contacts of newly diagnosed sputum smear-positive patients receiving anti-TB therapy from three hospitals in Accra were recruited, after providing written informed consent, between April 2012 and December 2014. In addition to demographic details, 2 mL of blood was collected from all participants for the QFT-GIT test for LTBI diagnosis. Results: Out of 112 eligible consenting participants, the QFT-GIT test was performed for 100 participants. The prevalence of LTBI (QFT-GIT positive) was 65%, with 32% being QFT-GIT negative and 3% indeterminate results. Contacts aged >15 years were more likely to be QFT-GIT positive than those aged >15 years, regardless of their Bacillus Calmette–Guerin status. There was significantly higher QFT-GIT test positivity in adult contacts who were parents, siblings, or spouses to index cases than in child contacts (P = 0.0016, P = 0.04, and P = 0.0003, respectively). Conclusion: The QFT-GIT test will be a useful tool for screening of TB contacts for LTBI in Ghana.
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Molecular typing of Mycobacterium Abscessus isolated from cystic fibrosis patients
Alberto Trovato, Rossella Baldan, Danila Costa, Tullia M Simonetti, Daniela M Cirillo, Enrico Tortoli
April-June 2017, 6(2):138-141
DOI:10.4103/ijmy.ijmy_33_17  PMID:28559514
Background: The possibility of inter-human transmission of Mycobacterium abscessus in cystic fibrosis centres has been recently hypothesized suggesting the need for the molecular characterization of strains isolated from such patients. Materials and Methods: One hundred and forty one isolates of M. abscessus grown from sputum samples of 29 patients with cystic fibrosis were genotyped resorting to variable number of tandem repeats (VNTR) determination and whole genome sequencing (WGS). Results: Out of 29 VNTR profiles, 15 were unique to the same number of patients while seven were shared by multiple patients. WGS showed that only two of the patients sharing common VNTR patterns were indeed infected by the same strain. The shared VNTR patterns were mostly present among the isolates of M. abscessus subsp. abscessus. Conclusion: As expected WGS showed a clearly higher discriminatory power in comparison with VNTR and appeared the only molecular epidemiology tool suitable to effectively discriminate the isolates of M. abscessus subsp. abscessus.
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Etiology and outcome of moderate-to-massive hemoptysis: Experience from a tertiary care center of North India
Ashish Bhalla, Ashok Kumar Pannu, Vikas Suri
July-September 2017, 6(3):307-310
Background: The aim of this study was to evaluate the etiology of hemoptysis in patients presenting to emergency department of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Method: Prospectively 110 patients presenting to the emergency department with history of hemoptysis were screened for a period of one and half years. Out of these, 64 patients having true hemoptysis were enrolled in the study. The patients were clinically evaluated with detailed history. Radiological evaluation included chest x rays and computerized tomogram. Sputum examination and bronchoscopy was done to establish the etiology. All the patients were conservatively managed using intravenous fluids, antibiotics, anti-tussive and anti-fibrinolytic drugs. Bronchial/pulmonary artery embolization was performed for controlling ongoing bleeding/re-bleeding. All the patients were followed up till discharge or death. Results: The mean age was 41.8 ± 15.16 years with male preponderance. Pulmonary tuberculosis (active/ sequel) was the most common etiology (65%), followed by community acquired pneumonia (10.93%), bronchiectasis (9.3%), carcinoma lung (7.18%) and miscellaneous causes (8.6%). Almost all patients (98%) had severe hemoptysis (>100 ml in 24 hours). Abnormalities in bronchial circulation were present in 59.4% and 14% of patients had pulmonary circulation abnormalities. 65% patients responded to conservative treatment. 23.4% patients under went intervention out of which 73.3% underwent bronchial artery embolization (BAE) and remaining 26.6% underwent pulmonary artery embolization (PAE). One patient died during hospital stay due to necrotizing pneumonia and another left hospital against medical advice (outcome unknown). Conclusions: TB (active/sequel) remains the most common cause of hemoptysis in patients admitted in emergency department. Non-TB causes like primary bronchiectasis, carcinoma lung and pneumonia are other important causes. Conservative management suffices in majority patients for controlling active bleed.
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Disseminated Mycobacterium avium complex in an immunocompetent host
Joseph M Yabes, Aaron Farmer, Todd Vento
April-June 2017, 6(2):202-206
DOI:10.4103/ijmy.ijmy_28_17  PMID:28559528
Disseminated Mycobacterium avium complex (DMAC) has historically been described in the immunocompromised. The current epidemiologic research suggests that the incidence of nontuberculous mycobacterial infections is increasing. We present a case of DMAC infection manifesting as hepatic granulomas in a 35-year-old immunocompetent female. This case suggests DMAC infection in a patient without traditional epidemiological risk factors.
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Screening of health-care workers for latent tuberculosis infection in a Tertiary Care Hospital
Anand Bimari Janagond, Vithiya Ganesan, GS Vijay Kumar, Arunagiri Ramesh, Prem Anand, M Mariappan
July-September 2017, 6(3):253-257
Background: Health-care workers (HCWs) are at increased risk of acquiring tuberculosis (TB) than the general population. While national-level data on the burden of TB in general population is available from reliable sources, nationally representative data on latent tuberculosis infection (LTBI) burden in HCWs in the high burden countries is lacking. Methods: A prospective study was carried out to assess the risk of TB infection among HCWs who directly engage in medical duties. HCWs were recruited between January 2014 and December 2015. A structured questionnaire was used for risk assessment of TB infection among HCWs, including sociodemographic characteristics (e.g., age, gender, period of professional work, and employed position), knowledge of TB prevention and control, and history of professional work. A single-step tuberculin skin test (TST) using 5 international units (IU; 0.1 ml) of tuberculin (purified protein derivative from Mycobacterium bovis Bacillus Calmette–Guérin [BCG]). TB infection was determined using a TST induration ≥10 mm as a cutoff point for TST positivity. TST-positive participants were further subjected to detailed clinical evaluation and chest radiography to rule out active TB. The associations between TB infection and the sociodemographic characteristics, duration of possible exposure to TB while on medical duties, BCG vaccination, and knowledge about TB were estimated using Chi-square test. A two-sided P < 0.05 indicated statistical significance. Results: A total of 206 eligible HCWs signed the informed consent and completed the questionnaires between January 2014 and December 2015. The age of the participants ranged from 18 to 71 years, with a mean age of 27.13 years. TST induration size (mean 6.37 mm) the TST results suggested that 36.8% (76/206) were infected with TB using a TST induration ≥10 mm as a cut-off point. All 76 TST-positive HCWs showed no evidence of active TB in clinical evaluation and chest radiography. However, during the study, two HCWs developed pulmonary TB (both TST baseline test negative). Statistical analysis suggested that age, duration of employment as a health-care professional, literacy status, and working in medical wards/OP/Intensive Care Unit were significantly associated with TB infection. Conclusions: Many studies propose serial tests of LTBI as effective occupational protection strategies. However, practically, it is not feasible because it has to be done at frequent intervals, but how frequently to be done is not clear. Another concern is even if found to have LTBI, there are no clear consensus guidelines about the treatment in high prevalence settings. The prevalence of LTBI is so high in countries like India that affected HCWs could not be exempted from working in high-risk areas. The depth of knowledge of TB prevention and control among HCWs should be improved by regular infection control training.
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