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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.
  33,519 1,737 20
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.
  20,252 1,688 12
SHORT COMMUNICATION
First detection of Mycobacterium triplex in Latin America
Carlos Eduardo Dias Campos, Cláudia Fontoura Dias, Gisela Unis, Paulo Cesar de Souza Caldas, Paulo Redner, Lucianade Distásio de Carvalho, Ana Paula Chaves Sobral Gomes, Marta Osório Ribeiro, Fátima Cristina Onofre Fandinho Montes, Enrico Tortoli, Jesus Pais Ramos
January-March 2016, 5(1):89-91
DOI:10.1016/j.ijmyco.2015.09.004  
In this study we describe the first isolation of Mycobacterium triplex in Latin America. This species causes infections in humans, with very few reports from around the world. We isolated two sputum specimens of a patient with a 6-year history of human immunodeficiency and tuberculosis treatment failure. All tests used confirmed M. triplex and the patient responded well to drug therapy for 18 months.
  15,864 120 5
REVIEW ARTICLES
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.
  13,472 2,104 12
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.
  10,569 1,023 4
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.
  9,252 1,322 22
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.
  8,926 1,109 9
CASE REPORTS
Mediastinal ganglionar tuberculosis postcardiac transplantation
Joćo Bruno Ribeiro Machado Lisboa, Guilherme de Abreu Rodrigues, Diego Corsetti Mondadori, Joćo Paulo Cassiano de Macedo, Orival De Freitas Filho, Paulo Manuel Pêgo-Fernades
January-March 2018, 7(1):101-103
DOI:10.4103/ijmy.ijmy_184_17  PMID:29516896
The diagnosis and treatment of tuberculosis (TB) in transplanted receivers presents several challenges. TB is an opportunistic infection with high morbidity and mortality in solid organs of transplanted patients, therefore, the diagnosis difficulties. A case of a 30-year-old male, heart transplanted patient, who after being submitted to mediastinoscopy, obtained a result of lymph node TB.
  9,626 222 -
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.
  8,861 820 5
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.
  8,985 285 -
ORIGINAL ARTICLES
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.
  8,044 532 1
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  
  8,237 260 1
“Fleeting pulmonary infiltrates in allergic bronchopulmonary aspergillosis” Misdiagnosed as tuberculosis
Shital Patil, Rajesh Patil
April-June 2018, 7(2):186-190
DOI:10.4103/ijmy.ijmy_57_18  PMID:29900899
Allergic bronchopulmonary aspergillosis (ABPA) is underdiagnosed and underevaluated routinely because of clinical and radiological overlap with tuberculosis (TB), especially in tropical setting with high TB burden countries like India. ABPA is the best-recognized manifestation of Aspergillus-associated hypersensitivity to Aspergillus antigens in patients with long-standing atopic asthma. ABPA with varied clinical presentation has been reported to occur in 20% of asthmatic patients admitted to hospitals and in 5% of all rhinitis cases. In this case report, we documented middle age male with known asthma case for many years with constitutional symptoms such as cough, fever, and shortness of breath diagnosed as TB and received anti-TB treatment for 4 weeks. Finally, we confirmed as a case of ABPA and documented complete clinical and radiological response to medical treatment with antifungals and systemic corticosteroids.
  7,372 345 1
ORIGINAL RESEARCH ARTICLES
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.
  6,973 723 6
ARTICLES
Evaluation of the Indian TrueNAT micro RT-PCR device with GeneXpert for case detection of pulmonary tuberculosis
Chaitali Nikam, Mubin Kazi, Chandrasekhar Nair, Majula Jaggannath, M Manoj, R Vinaya, Anjali Shetty, Camilla Rodrigues
July-September 2014, 3(3):205-210
DOI:10.1016/j.ijmyco.2014.04.003  
To evaluate the performance of TrueNAT (RT Micro PCR device) assay in comparison with GeneXpert on sputum samples from pulmonary cases of tuberculosis. 274 samples were processed to detect MTB by ZN smear examination, MGIT culture and molecular methods that included RT-PCR (ABI 7500 & TrueNAT) and GeneXpert for case detection of TB. The overall performance of the test with MGIT(Mycobacterium Growth Indicator Tube) culture as gold standard, sensitivity of smear, RT PCR/TrueNAT and Genexpert was 61.5% (CI:53.3–69.3%), 94.7% (CI:89.8–97.6%) & 96.0% (CI: 91.5–98.5%), respectively. Amongst the S+ (108) samples, RT-PCR/TrueNAT and GeneXpert showed a sensitivity of 99% (CI:94.9%–99.8%) and 100% (98.6%–100.0%), respectively. High concordance was observed between GeneXpert and TrueNAT for case detection of TB. The GeneXpert MTB/RIF test was independent on the user's skills. It has a short turn-around time and simultaneously detects RIF resistance with M. tuberculosis in less than 3 h. The TrueNAT MTB has good sensitivity and specificity in case detection with hands on time of less than 3 h as well as fits the requirements in resourcelimited health care settings. Larger, multi-site studies are required to obtain better estimates of the performance of TrueNAT MTB.
  7,206 431 33
ORIGINAL ARTICLES
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
DOI:10.4103/ijmy.ijmy_87_17  
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.
  6,765 644 3
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.
  6,510 845 6
ORIGINAL ARTICLES
Detection of multidrug-resistant tuberculosis from stored DNA Samples: A multicenter study
Marie Sylvianne Rabodoarivelo, A Brandao, MC Cergole Novella, AG C. Bombonatte, B Imperiale, N Rakotosamimanana, N Morcillo, V Rasolofo, JC Palomino, A Martin
January-March 2018, 7(1):40-44
DOI:10.4103/ijmy.ijmy_193_17  PMID:29516884
Background: In low-income countries, rapid detection of tuberculosis (TB) drug resistance is often restricted by the difficulties of transporting and storing sputum samples from remote health centers to the reference laboratories where molecular tests are available. The aim of this study was to evaluate the performance of four transport and storage systems for molecular detection of rifampicin (RIF) and isoniazid (INH) resistance. Methods: This was a multicenter study. Molecular detection of RIF and INH resistance was performed directly from smear-positive TB sputa spotted on a slide, FTA card, GenoCard, and ethanol using the Genotype MTBDRplus assay. The performance of the DNA extraction method from each storage support to detect drug resistance was assessed by calculating their sensitivity and specificity compared to the phenotypic method. Results: From all sites, the overall sensitivity and specificity for RIF-resistance detection was 88% and 85%, respectively, for slides, 86% and 92%, respectively, for GenoCard, 87% and 89%, respectively, for FTA card, and 88% and 92%, respectively, for ethanol. For INH-resistance detection, the overall sensitivity and specificity was 82% and 90%, respectively, for slides, 85% and 96%, respectively, for GenoCard, 86% and 92%, respectively, for FTA card, and 86% and 94%, respectively, for ethanol. Conclusion: Smear slides and filter cards showed to be very useful tools to facilitate DNA extraction from sputum samples with the potential to accelerate the detection of drug resistance in remote areas.
  6,747 318 4
Pulmonary functions' assessment in post-tuberculosis cases by spirometry: Obstructive pattern is predominant and needs cautious evaluation in all treated cases irrespective of symptoms
Shital Patil, Rajesh Patil, Anil Jadhav
April-June 2018, 7(2):128-133
DOI:10.4103/ijmy.ijmy_56_18  PMID:29900887
Background: Approximately 30%–40% patients suffer with lung function issues in spite of successful treatment outcome; and these problems are less documented routinely. Methods: Prospective multicentric study conducted during July 2013–June 2017, to find pulmonary function assessment in posttuberculosis (TB) cases irrespective of their symptoms, included 500 cases in symptomatic and asymptomatic group and subjected to inclusion and exclusion criteria. All cases were subjected to spirometry analysis. Statistical analysis was done using Chi-square test. Results: In spirometry assessment of symptomatic post-TB cases, obstructive pattern was predominant type documented in 42% cases. In spirometry assessment of asymptomatic post-TB cases, obstructive pattern is documented in 32%, mixed pattern in 14%, and normal spirometry is documented in 46% cases. In spirometry assessment in symptomatic and asymptomatic cases, obstructive pattern is documented in 210 cases and 160 cases, respectively (P < 0.00001). Abnormal lung function is documented in 70% and 54% in symptomatic and asymptomatic post-TB cases, respectively (P < 0.00001). Conclusions: Lung function impairment is known to occur after pulmonary TB irrespective of duration of treatment and outcome of disease. Obstructive lung disease is the predominant lung function impairment in symptomatic cases. Significant number of asymptomatic cases are also having obstructive pattern of lung function in spirometry analysis.
  6,212 846 2
CASE SERIES
Tuberculous myocarditis is not always fatal: Report of three confirmed cases with uneventful outcome
Fares Al-Jahdali, Abdullah Al-Harbi, Salim Baharoon, Majed Al-Gamdi, Hamdan AL-Jahdali
January-March 2017, 6(1):111-115
DOI:10.4103/ijmy.ijmy_9_17  PMID:28317817
Tuberculosis (TB) is a leading cause of death worldwide. It can affect any organ. However, cardiac involvement is extremely rare. Anti-TB therapy has been proved to be effective and curative in majority of TB cases except TB myocarditis, where it is found to be fatal. We describe three cases with confirmed TB with impaired left ventricular systolic function and low ejection fraction. All three cases improved clinically and left ventricular function returned to normal within a few weeks after the commencement of TB therapy.
  6,541 508 5
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.
  5,809 1,170 18
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.
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ORIGINAL ARTICLES
A comparison of intradermal test with recombinant tuberculosis allergen (diaskintest) with other immunologic tests in the diagnosis of tuberculosis infection
Anna Starshinova, Viacheslav Zhuravlev, Irina Dovgaluk, Alexandr Panteleev, Vera Manina, Ulia Zinchenko, Evgenia Istomina, Maria Pavlova, Piotr Yablonskiy
January-March 2018, 7(1):32-39
DOI:10.4103/ijmy.ijmy_17_18  PMID:29516883
Background: The WHO strategy for eradication of tuberculosis (TB) by 2035 (The End TB Strategy) is aimed at an early and precise diagnosis and subsequent effective treatment of TB patients. Currently, there is no gold standard for the diagnosis of latent TB infection. This study evaluated the diagnostic capabilities of a new intradermal test using recombinant TB allergen (Diaskintest) compared with tuberculin skin test (TST) and commercial TB interferon-gamma release assays (IGRAs). Methods: A post-hoc data analysis that involved examining 860 HIV-negative, bacillus Calmette–Guérin (BCG)-vaccinated persons aged 1–65 years who visited the TB health-care institutions of Saint Petersburg to rule out or confirm an active TB was conducted from 2011 to 2016. Results: A high degree of consistency of the Diaskintest results with the enzyme-linked immunospot and QuantiFERON-TB Gold In-Tube test (ELISPOT and QFT) results was observed in the examined pediatric population (n = 696), with a Diaskintest cutoff ≥5 mm: the kappa consistency indices were 1.000 and 0.937, for ELISPOT and QFT, respectively. A high sensitivity of Diaskintest, comparable with the IGRA tests, was observed in patients with a confirmed TB diagnosis in all age groups. The sensitivity of Diaskintest in patients of the TB/MTB + group aged 18 years and older was 88.7%; of ELISPOT, 90.6%; of QFT, 87.0%. The conducted analysis has shown a high concordance of results of the commercial TB tests in adult HIV-negative patients (n = 164) with a Diaskintest cutoff ≥5 mm: the kappa indices were 0.805 and 0.636 (Diaskintest vs. ELISPOT and QFT, respectively) among BCG-vaccinated people. Conclusion: According to the WHO recommendations, replacing the TST by IGRAs is not recommended as a public health intervention in resource-constrained settings because the IGRA tests are more costly and technically complex to conduct than the TST. Diaskintest has comparable complexity to the TST and its performance is close to that of IGRA in a BCG-vaccinated population. Thus, our study demonstrates that replacing the TST by Diaskintest can be recommended as a public health intervention in resource-constrained and universal BCG vaccination settings.
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Risk factors associated with unsuppressed viral load in HIV-1 infected patients at the first antiretroviral therapy in Morocco
Titou Hicham, Elkassimi Ilyas, Hanafi Tarik, Baba Noureddine, Boudi Omar, Frikh Rachid, Hjira Naoufal, Boui Mohammed
April-June 2019, 8(2):113-117
DOI:10.4103/ijmy.ijmy_41_19  PMID:31210151
Background: Nonsuppression of viral load (VL) in HIV-infected patients on antiretroviral therapy (ART) is associated with increased HIV transmission and poor survival. The objective of this work was to evaluate the factors associated with the unsuppressed VL (VL >400 copies/ml) in HIV-1-infected patients after 6 months of the first-line ART. Methods: This was a retrospective cohort study of 181 patients living with HIV-1 on ART in Dermatology and Venereology Department of Mohamed V Military Teaching Hospital of Rabat, during the period between January 1, 2007, and January 1, 2017. Associated factors were identified through a logistic regression model. Results: Of the 181 patients, 76% were men. At inclusion, the median age was 35 years. Five variables (male sex, initial fasting glucose >1.1 g/l, alcoholism, smoking, and initial VL >10,000 copies/ml) were significantly associated (P < 0.05) with unsuppressed VL. In multivariate analysis, smoking (relative risk [RR]: 4.27, 95% confidence interval [CI]: 1.67–10.89) and initial VL >10,000 (RR: 9.78, 95% CI: 2.40–39.73) were associated independently with unsuppressed VL. Conclusion: Approximately 83% of the patients in the cohort had been able to suppress VL after 6 months of the first-line ART. Smoking and high initial VL were independent risk factors of unsuppressed VL. This work highlights the importance of developing and evaluating targeted interventions for patients at risk of unsuppressed VL on ART.
  5,795 656 -
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.
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