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REVIEW
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.
  11,260 892 5
REVIEW ARTICLES
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.
  6,210 932 6
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
DOI:10.4103/ijmy.ijmy_70_17  
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.
  6,037 964 1
ORIGINAL RESEARCH ARTICLES
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.
  5,770 682 -
ORIGINAL ARTICLES
Cervical tuberculous lymphadenitis: Clinical profile and diagnostic modalities
Hitender Gautam, Sonu Kumari Agrawal, Santosh Kumar Verma, Urvashi B Singh
July-September 2018, 7(3):212-216
DOI:10.4103/ijmy.ijmy_99_18  PMID:30198498
Background: Tuberculosis is a major global health problem. Tuberculous lymphadenopathy is a most common form of extrapulmonary tuberculosis (EPTB), constitutes 35% of all cases of EPTB. Due to the paucibacillary nature of specimens, smear microscopy and culture offer low sensitivity. Methods: The aim of the present study was to find the clinicodemographic profiles and comparing the performance of Xpert MTB/RIF, conventional polymerase chain reaction (PCR), mycobacteria growth indicator tube (MGIT) 960, histopathological examination, and clinical follow-up of patients in diagnosing of smear-negative tuberculous lymphadenopathy. Results: A total of 140 clinically suspected cervical tuberculous lymphadenitis cases were enrolled in this study. MGIT-960 culture, conventional PCR, and Xpert MTB/RIF were performed. Most of the patients presented with unilateral (87.14%), single (81.42%), matted (87.85%) lymph nodes, 3 cm–6 cm (52.14%), commonly in the right side (68.02%), and associated lung lesion was found in 12.86% of cases. The detection rates of Mycobacterium tuberculosis complex (MTBC) by Xpert MTB/RIF, conventional PCR, and MGIT were 25.71%, 20.71%, and 17.85%, respectively. Both the tests: Xpert MTB/RIF and PCR, PCR and MGIT, Xpert MTB/RIF and MGIT were positive in 15.71%, 15.71%, and 11.42% of cases, respectively. Most of the patients (74.1%) were cured with 6 months of antitubercular drugs. Conclusion: Clinicians often face the diagnostic dilemmas presented in the study. Individual modalities of the diagnosis are available, but all have drawbacks with varied sensitivity and specificity. Combining the available clinical, radiological, and microbiological modality to reach early diagnosis can go a long way to avoid misdiagnosis and unnecessary delay in treatment, especially in cases, without the pulmonary involvement and fulfilling the aim of National Tuberculosis Control Programme for EPTB cases.
  3,723 464 1
REVIEW ARTICLES
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
DOI:10.4103/ijmy.ijmy_85_17  
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.
  3,106 734 7
ORIGINAL RESEARCH ARTICLES
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.
  3,095 679 4
CASE REPORTS
Pulmonary tuberculosis initially presented by hoarseness
Gil Chai Lim, Jaechun Lee
April-June 2012, 1(2):94-95
DOI:10.1016/j.ijmyco.2012.02.003  
  3,583 126 -
ORIGINAL ARTICLES
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
DOI:10.4103/ijmy.ijmy_54_17  
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.
  3,267 416 2
CASE REPORTS
Bilateral inguinal lymphadenopathy presenting as tuberculosis in a case of carcinoma rectum
Sunil Vyas, Narendra Umashankar, Nirupama Kothari, Vinay Vyas
October-December 2017, 6(4):410-411
DOI:10.4103/ijmy.ijmy_134_17  PMID:29171459
Isolated bilateral inguinal tubercular lymphadenitis is a very rare presentation. A 59-year-old male, on treatment for Carcinoma rectum (T3 N1 M0) presented with bilateral inguinal lymphadenopathy. Metastasis and tuberculosis were considered for differentials. FNAC of the lesion showed Necrotizing granulomatous lymphadenitis. There was regression of the lesion on both sides after two months of Anti-tubercular Therapy. Even though Metastasis is the commonest cause of inguinal lymphadenopathy in a case of carcinoma rectum, Tuberculosis needs to be considered in the differential diagnosis in our country. FNAC/Biopsy can be considered in those patients to confirm the diagnosis.
  3,478 127 -
ORIGINAL RESEARCH ARTICLES
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.
  2,930 589 4
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.
  3,043 420 3
ORIGINAL ARTICLES
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.
  2,944 502 2
Rapid laboratory diagnosis of pulmonary tuberculosis
Prasanna Bhirud, Ameeta Joshi, Nilma Hirani, Abhay Chowdhary
July-September 2017, 6(3):296-301
DOI:10.4103/ijmy.ijmy_61_17  
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.
  2,839 569 4
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.
  2,705 538 5
Uric acid levels in patients on antituberculosis drugs in the southwest Region of Cameroon
Benjamin David Thumamo Pokam, Jude E Enoh, Aniekan-Augusta O Eyo, Nse O Umoh, Prisca W Guemdjom
January-March 2018, 7(1):89-91
DOI:10.4103/ijmy.ijmy_161_17  PMID:29516892
Background: Antituberculosis drugs (ATDs) efficiently combat Mycobacterium tuberculosis either through direct molecular interactions or those of its metabolites. However, a variety of adverse effects have been reported, leading to frequent interruptions of treatment. To investigate the possible metabolic disturbances resulting from antituberculosis (TB) treatment, the uric acid (UA) level of patients on ATDs was measured in the southwest region of Cameroon. Methods: This hospital-based cross-sectional study involved 96 TB patients on ATDs and 32 controls who were neither on ATDs nor any other treatment that could increase UA levels. The hospital records of consenting participants were reviewed for medical history and questionnaires were issued. About 2 ml venous blood was collected and analyzed using spectrophotometers to determine UA levels. Results: Hyperuricemia was observed in 56/96 (58.3%) of the studied group as compared with 4/32 (12.5%) in the control group (P < 0.001). Our results indicated that treatment duration was significantly associated with hyperuricemia (P = 0.0016) while gender (P = 0.1275) was not. Conclusion: Hyperuricemia is associated with ATDs, with treatment duration being a significant factor. The disorder should be closely monitored, especially during the intensive phase of treatment.
  2,980 242 -
ORIGINAL RESEARCH ARTICLES
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).
  2,656 491 -
ORIGINAL ARTICLES
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
DOI:10.4103/ijmy.ijmy_68_17  
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.
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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
DOI:10.4103/ijmy.ijmy_91_17  
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.
  2,597 441 3
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.
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Mycobacterium abscessus complex: Natural history and treatment outcomes at a tertiary adult cystic fibrosis center
Emma Tippett, Samantha Ellis, John Wilson, Tom Kotsimbos, Denis Spelman
April-June 2018, 7(2):109-116
DOI:10.4103/ijmy.ijmy_55_18  PMID:29900884
Background: Mycobacterium abscessus complex (MAbsC) is a significant management dilemma when taking care of patients with cystic fibrosis (CF). Methods: We undertook a retrospective cohort analysis of all CF patients in whom MAbsC was isolated from 2005 to 2014. The natural history of MAbsC was determined and clinical factors examined in an attempt to predict transient compared to persistent colonization. Results: No correlation was found between recurrent MAbsC isolation and clinical factors such as body mass index, respiratory function, or age. Over two-thirds of our cohort cleared MAbsC colonization with no intervention and no consistent effect on lung function was identified. Four CF patients were initiated on treatment with only one successful outcome. Conclusion: This analysis demonstrates there are no clear predictors of those CF patients who will become persistently colonized with MAbsC and that a significant proportion will spontaneously clear carriage. As treatment success rate is poor, more work is urgently required in improving patient outcomes.
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CASE REPORTS
Various cutaneous tuberculosis with rare clinical manifestations: A case series
Hendra Gunawan, Pati Aji Achdiat, Reti Hindritiani, Erika Dewi Essary, Lulu Dwiarti Ningtias, Elfrida Putri Siregar, Putri Reno Sori, Dia Febrina
July-September 2018, 7(3):288-291
DOI:10.4103/ijmy.ijmy_65_18  PMID:30198513
Cutaneous tuberculosis (TB) has several clinical manifestations. The most common forms include cervical scrofuloderma and plaque type of lupus vulgaris (LV), otherwise the rare cases including inguinal scrofuloderma, ulcerative LV, and acute miliary TB. The highlight of this case series was to report various rare clinical manifestations of cutaneous TB.
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ORIGINAL ARTICLES
Mycobacterium tuberculosis Strains H37ra and H37rv have equivalent minimum inhibitory concentrations to most antituberculosis drugs
Marc Tobias Heinrichs, Robert Justin May, Fabian Heider, Tobias Reimers, Sherwin Kenneth B. Sy, Charles Arthur Peloquin, Hartmut Derendorf
April-June 2018, 7(2):156-161
DOI:10.4103/ijmy.ijmy_33_18  PMID:29900893
Background: Mycobacterium tuberculosis (Mtb) strains H37Ra and H37Rv are commonly used to study new and re-evaluate old antituberculous agents with respect to their pharmacodynamic effects in vitro. The differences in membrane proteins and, in particular, differences in carrier proteins between Mtb H37Ra and Mtb H37Rv may have an impact on antibiotic potency. The question of whether H37Ra can be used as a reliable surrogate for H37Rv and clinical strains has not been addressed sufficiently. The purpose of this study is to provide a full comparison of susceptibility data of the most common antituberculosis (TB) agents against both Mtb strains. Methods: In addition to a literature review, in vitro checkerboard susceptibility study was conducted comparing the in vitro minimum inhibitory concentration (MIC) of 16 common antituberculous drugs against H37Ra and H37Rv. Heifets–Sanchez TB agar drug susceptibility plates were utilized. Results: Half of the antibiotics demonstrated similar growth inhibition against both strains, while slightly differing MIC values were found for 7 of 16 drugs. With the exception of rifampicin, no marked difference in MIC against H37Ra and H37Rv was observed. Conclusion: While neither the attenuated (H37Ra) nor the virulent strain (H37Rv) is a clinical strain, both strains predicted MICs of clinical isolates equally well, when comparing the current in vitro results to clinical susceptibility data in the literature. H37Ra comes with the benefits of lower experimental costs and less administrative barriers including the requirement of a biosafety Level III environment.
  2,478 459 7
ORIGINAL RESEARCH ARTICLES
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.
  2,473 428 6
ORIGINAL ARTICLES
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
DOI:10.4103/ijmy.ijmy_89_17  
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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