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   Table of Contents - Current issue
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July-September 2022
Volume 11 | Issue 3
Page Nos. 229-342

Online since Monday, September 12, 2022

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REVIEW ARTICLE  

Role of IL 6 as a biomarker in the diagnosis of tuberculous meningitis – A systematic review Highly accessed article p. 229
P Kruthika
DOI:10.4103/ijmy.ijmy_101_22  
Background: Tuberculous meningitis (TBM) is the most common and serious form of central nervous system tuberculosis (TB) with high morbidity and mortality. Following the encounter of tubercle bacilli by microglial cells, inflammatory process sets in and series of cytokines are secreted such as tumor necrosis factor, interleukin-6 (IL6), and interferon γ. The following study was undertaken with the aim of systemically reviewing the diagnostic and prognostic evidence of IL6 in TBM. Methods: After a thorough search of databases for the articles with IL6 association in TBM published from 2001 onwards to September 2021. Articles were identified and assessed according to the inclusion and exclusion criteria. Excel spreadsheets were used for the extraction of data and analysis. Results: A total of 10 studies were included for review which focused on IL6 in the role of TBM diagnosis. All the age group persons of both sexes were included in the study. The experiment was conducted mostly in the developing countries. The range of measured IL6 values was very wide and difficult to interpret. Conclusion: TBM patients' IL 6 was higher than healthy controls in all the studies mentioned, but the results of cerebrospinal fluid IL6 and serum IL6 were less consistent. Due to a small number of prospective studies, it was not possible to analyze the IL6 cut-off value to diagnose TB. Further studies are required to provide information on IL6 as biomarker in the diagnosis of TBM.
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ORIGINAL ARTICLES Top

The diagnostic yield and characteristics of bronchoalveolar lavage in suspected nontuberculous mycobacterial pulmonary disease p. 236
Shigehisa Kajikawa, Eisuke Fujishiro, Toshio Kato, Hiroyuki Tanaka, Etsuro Yamaguchi, Akihito Kubo, Satoru Ito
DOI:10.4103/ijmy.ijmy_77_22  
Background: Bronchoalveolar lavage (BAL) has widely been used to manage respiratory diseases including respiratory infections. The aim of this study was to evaluate the diagnostic yield of BAL for detecting nontuberculous Mycobacterium (NTM). Methods: We retrospectively reviewed the records of 54 patients who underwent bronchoscopy due to suspected NTM pulmonary disease. Positive culture results of respiratory specimens were defined as NTM pulmonary disease. For BAL, two or three aliquots of 50 mL (total 100 or 150 mL) of sterile normal saline were instilled through bronchoscope. Results: NTM was detected in 31 of 54 (57.4%) patients. The detection rates were not different between the patients who underwent bronchoscopy with BAL (24 of 39, 61.5%) and those without (7 of 15, 46.7%) (P = 0.437). BAL fluid was mostly neutrophil dominant in both positive and negative NTM culture groups. In the subgroup analysis of 33 patients who underwent both the BAL and anti- glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody measurements, 12 of 19 (63.2%) positive Mycobacterium avium complex (MAC) culture patients and 8 of 14 (57.1%) negative MAC culture patients were positive for anti-GPL-core IgA antibody (seropositive) (P = 0.991). There was no severe complication related to BAL. Conclusions: The diagnostic yield of BAL with ≥100 mL sterile saline was not superior to that of bronchial wash or sputum aspiration in patients with suspected NTM pulmonary disease. Patients with seropositive but negative culture results for MAC suggest pseudonegative for pulmonary MAC disease.
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Multiple pathogens contribute to human immunodeficiency virus-related sepsis in addition to Mycobacterium tuberculosis: A prospective cohort in Tanzania p. 241
Donatus Bonphace Tsere, Gabriel Mkilema Shirima, Brian S Grundy, Scott K Heysell, Stellah G Mpagama, Shabani Ramadhani Mziray, Peter M Mbelele
DOI:10.4103/ijmy.ijmy_80_22  
Background: Mortality from tuberculosis (TB) sepsis is common among patients living with human immunodeficiency virus (PLHIV). We aimed to detect M. tuberculosis (MTB) and additional sepsis etiologies, and mortality determinants in PLHIV. Methods: This prospective cohort study consented and followed-up PLHIV for 28 days in northern Tanzania. From May through December 2021, patients provided urine and sputum for TB testing in lateral-flow lipoarabinomannan (LF-LAM) and Xpert® MTB/RIF. Bacterial blood culture, cryptococcal antigen, malaria rapid diagnostic, C-reactive-protein (CRP), and international normalized ratio (INR) tests were also performed. Sepsis severity was clinically measured by Karnofsky and modified early warning signs (MEWS) scores. Anti-TB, broad-spectrum antibiotics, and antimalarial and antifungal agents were prescribed in accordance with Tanzania treatment guideline. An independent t-test and Chi-square or Fisher's exact tests compared means and proportions, respectively. P < 0.05 was statistically significant. Results: Among 98 patients, 59 (60.2%) were female. Their mean (standard deviation) age was 44 (12.9) years. TB detection increased from 24 (24.5%) by Xpert® MTB/RIF to 36 (36.7%) when LF-LAM was added. In total, 23 (23.5%) patients had other than TB etiologies of sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Cryptococcus spp., and Plasmodium spp. Twenty-four (94.4%) of 36 patients with TB had higher CRP (≥10 mg/l) compared to 25 (40.3%) non-TB patients (P < 0.001). Nine (9.2%) patients died and almost all had INR ≥1.8 (n = 8), Karnofsky score <50% (n = 9), MEWS score >6 (n = 8), and malnutrition (n = 9). Conclusions: MTB and other microbes contributed to sepsis in PLHIV. Adding non-TB tests informed clinical decisions. Mortality was predicted by conventional sepsis and severity scoring, malnutrition, and elevated INR.
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Scientometric analysis of the world scientific production on tuberculosis associated with COVID-19 p. 249
Jorge Nieto-Chumbipuma, Luis Silva-Reategui, Alicia Fernandez-Giusti, John Barja-Ore, Yesenia Retamozo-Siancas, Frank Mayta-Tovalino
DOI:10.4103/ijmy.ijmy_81_22  
Background: Nowadays, tuberculosis and COVID-19 are the principal infections around the world. This study aimed to determine the global scientific production on COVID-19 associated to tuberculosis during the period 2019–2020. Methods: For the collection of metadata on COVID-19 associated to tuberculosis, the Scopus database was used, considering the period 2019–2020, with the last day of update being September 13, 2021. The main authors, countries, institutions, journal metrics, and documents were extracted. The Scival tool was used for the scientometric analysis of the data. Results: A total of 464 papers were retrieved where it was found that universities in South Africa, the United States, and England led the world's scientific production. The International Journal of Tuberculosis and Lung Disease was the journal with the highest production and The Lancet Global Health was the journal with the most citations per publication. On the other hand, most papers were published in Q1 journals, with infectious diseases within the area of medicine being the most addressed. Conclusion: South African universities lead the world in scientific output. Most of the research on this topic has been published in Q1 journals, with collaboration being largely national. Further analysis is needed in the aftermath of the pandemic.
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Effect of Ultraviolet-c (UVc) light and ozone on the survival of Mycobacterium abscessus complex organisms associated with cystic fibrosis p. 256
John Edmund Moore, Beverley Cherie Millar
DOI:10.4103/ijmy.ijmy_87_22  
Background: Members of the Mycobacterium abscessus complex have now emerged as clinically significant respiratory pathogens in people with cystic fibrosis (CF), potentially leading to increased disease severity, antibiotic treatment, and persistence dilemmas. Many of these species are resistant to disinfectants and biocides commonly used to clean and disinfect the hospital environment, thus necessitating the need to examine innovative ways to eliminate these organisms from such environments. It was, therefore, the aim of this study to examine the individual effect of ultraviolet-c (UVc) light (λ = 254 nm) and ozone (O3) on the growth of the M. abscessus complex organisms, as well as on seven other clinically significant CF pathogens, including Achromobacter spp., Burkholderia gladioli, Burkholderia cenocepacia, Burkholderia multivorans, Pseudomonas aeruginosa, Staphylococcus aureus, and Stenotrophomonas maltophilia. Methods: Bacterial isolates (n = 46), including M. abscessus complex (n = 6) (M. abscessus subsp abscessus [n = 2], M. abscessus subsp. bolletii [n = 2], M. abscessus subsp. massiliense [n = 2]), and other CF pathogens (n = 40) including Achromobacter spp., B. gladioli, B. cenocepacia, B. multivorans, P. aeruginosa, S. aureus, and S. maltophilia, were exposed for 1 h to UVc light (254 nm), as well as to ozone (O3; 26 ppm). Results: UVc light inactivated all M. abscessus complex organisms (n = 6), as well as the 40 isolates from the other genera and species. No bacterial species tested was able to survive the UVc treatment. O3 was unable to inactivate all isolates of M. abscessus subsp. abscessus (n = 2), M. abscessus subsp. bolletii (n = 2), and one isolate of M. abscessus subsp. massiliense, but killed one strain of M. abscessus subsp. massiliense. Overall, O3 inactivated only 20% of total isolates, allowing the posttreatment growth of the remaining 80% of isolates. There was no difference in the growth dynamic of P. aeruginosa from the environmental waters which had received O3 treatment and the control (untreated with O3). Bacterial growth, while occurring post-O3 treatment, was not as prolific in all remaining organisms, as in the untreated controls, demonstrating some but limited antibacterial effect. Conclusions: From the data presented by this study, UVc light at 254 nm was effective at eliminating all organisms examined, including members of the M. abscessus complex. Given the refractory nature of these organisms against conventional wet chemical disinfection, UVc potentially offers a physical method to control and eliminate the survival of these organisms on health-care surfaces and fomites. For many CF species examined in this study, these data represent the first reports of the organisms susceptibility to UVc light. Further work is now required to establish time/distance parameters incorporated into newly designed innovative devices, to allow disinfection protocols to be optimized, and delivered to exploit this vulnerability with these nontuberculous mycobacterial organisms, as well as with the other bacterial species examined.
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Treatment Outcomes of Multidrug-Resistant Tuberculosis Patients in East Java, Indonesia: A Retrospective Cohort Analysis p. 261
Hardini Tri Indarti, Erna Kristin, Soedarsono Soedarsono, Dwi Endarti
DOI:10.4103/ijmy.ijmy_86_22  
Background: The drug regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) has lower potency, is more costly, and has a greater risk of adverse effects than first-line anti-TB drugs. We aimed to compare the treatment outcomes of patients using standard shorter regimen (STR regimen) versus bedaquiline (BDQ)-containing individual regimen in a high TB-burden setting. Methods: This was a retrospective cohort study using secondary data from the medical records in the hospital. The study population were patients with MDR-TB who started treatment in 2016–2018. Treatment outcomes were classified as successful (cured/completed treatment) or unsuccessful (failure/death/loss to follow-up/not evaluated). Categorical data were presented as frequencies and percentage, whereas continuous data were presented as mean± standard deviations. Risk ratio (RR) was obtained by using the Chi-square statistical test with 95% confidence interval (CI) and P < 0.05 set as a significant result. Results: We included 99 patients out of 444 registered patients in 2016–2018. The overall success proportion was 41.4%. Success was more likely in patients who received BDQ regimen than those receiving STR regimen (52.9% vs. 35.4%, RR: 1.496, 95% CI: 0.948–2.362). Factors that influenced the treatment outcomes were smear status and sputum culture status. Conclusions: The success rate of the STR regimen and the BDQ regimen in this study is still below the national and global figures due to the high rate of lost to follow-up. The success was higher in the BDQ regimen, although not statistically significant. Further research is needed on adverse effects, quality of life, and costs during treatment.
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The Utility of a real-time polymerase chain reaction kit for differentiating between Mycobacterium tuberculosis and the Beijing familythe p. 268
Taeuk Kang, Da-Gyum Lee, Jihee Jung, Sungweon Ryoo
DOI:10.4103/ijmy.ijmy_99_22  
Background: Tuberculosis (TB) is a severe public health challenge in Korea. Of all Mycobacterium tuberculosis (M. tb) strains, the Beijing genotype strain reportedly correlates with hypervirulence and drug resistance. Hence, an early identification of the Beijing genotype strain of M. tb plays a significant role in initial TB treatment. Kogenebiotech® (KoRT-polymerase chain reaction [PCR]) has developed a real-time PCR 17 18 kit to determine the Beijing genotype strain classified as M. tb. To determine the feasibility of the commercially produced KoRT-PCR kit in identifying the M. tb strain. Methods: We used 100 clinical isolates of M. tb and 100 non-M. tb samples for the assessment. We evaluated the overall concordance between the KoRT-PCR kit and the mycobacterial interspersed repetitive unite variable number tandem repeat typing kit (GenoScreen, Lille, France). Moreover, we measured the detection limits based on the chromosomal DNA copies for the KoRT-PCR kit. In addition, we determined the reproducibility among individual technicians using the KoRT-PCR. Results: The KoRT-PCR kit successfully discriminated all M. tb (confidence interval [CI]: 96.38%–100.00% for both sensitivity and specificity) and Beijing genotype strain (CI: 95.70%–100.00% for sensitivity and 96.87%–100.00% for specificity). We confirmed no significant deviation in the reproducibility between the technicians. Conclusions: The KoRT-PCR kit displayed sufficient capability of discriminating the Beijing genotype strain, which enabled the rapid identification of the Beijing genotype strain from the M. tb clinical isolates.
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Growth and division mechanisms by which genetic resisters emerge from the rifampicin-surviving population of differentially antibiotic-susceptible mycobacterial subpopulations p. 273
Kishor Jakkala, Avraneel Paul, Rashmi Ravindran Nair, Sharmada Swaminath, Atul Pradhan, Parthasarathi Ajitkumar
DOI:10.4103/ijmy.ijmy_88_22  
Background: We recently reported the de novo emergence of unusually high numbers of antibiotic resisters from the in vitro cultures of Mycobacterium tuberculosis and Mycobacterium smegmatis surviving in the presence of minimum bactericidal concentration (MBC) of antituberculosis antibiotics. The resisters emerged due to multiple asymmetric divisions of elongated mother cells containing multiple nucleoids and multiple septae. We had earlier found a minor subpopulation of short-sized cells (SCs) and a major subpopulation of normal-sized cells (NCs) (10% and 90%, respectively, of the whole population), with significant difference in antibiotic susceptibility and resister generation frequency, in the in vitro cultures of M. tuberculosis, M. smegmatis, and Mycobacterium xenopi, as well as in pulmonary tuberculosis patients' sputum. However, the mechanisms of growth and division promoting the emergence of antibiotic resisters from these subpopulations remained unknown. Therefore, here, we took up the first-time study to find out the mechanism of growth and division by which antibiotic resisters emerge from the antibiotic-surviving population of the two subpopulations of M. smegmatis. Methods: M. smegmatis SCs and NCs were fractionated from mid-log phase cultures using Percoll gradient centrifugation; their purity was checked and exposed to 10×, 2×, and 0.4× MBC of rifampicin for 120 h. The colony-forming units (CFUs) were determined on rifampicin-free plates for the total population and on rifampicin-containing plates for scoring rifampicin resisters. The phenotype and the morphology of the cells at various stages of the exposure were determined using transmission electron microscopy. The dynamic growth and division mechanisms of the cells to emerge as rifampicin resisters were monitored using live-cell time-lapse imaging. The rifampicin resisters were sequenced for mutations in the rifampicin resistance determining region of rpoB gene. Statistical significance was calculated using two-tailed paired t-test, with *P ≤ 0.05 and **P ≤ 0.01. Results: Multinucleated and multiseptated elongated cells emerged from their respective antibiotic-surviving populations. They produced a large number of sibling-daughter cells through multiple asymmetric divisions in short durations, showing abnormally high spurts in CFUs of antibiotic resisters. The CFUs were several-fold higher than that expected from the mass-doubling time of the subpopulations. Despite this commonality, the subpopulations showed specific differences in their response to different multiples of their respective MBC of rifampicin. Conclusions: Mycobacterial subpopulations come out of rifampicin stress by undergoing multiple nucleoid replications, multiple septation for nucleoid segregation, and acquisition of antibiotic target-specific mutations, followed by multiple asymmetric divisions to generate unusually a large number of rifampicin resisters. Because we had earlier shown that SCs and NCs are present in the pulmonary tuberculosis patients' sputum, the present findings have clinical relevance on the mechanism of emergence of antibiotic-resistant strains from mycobacterial subpopulations.
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Analysis of a tuberculosis outbreak in an office: Hokkaido, Japan, 2019–2020 p. 287
Satomi Nitta, Kensaku Terada, Akemi Kurokawa, Ryo Yamaguchi, Munetaka Tateishi, Masaki Ota, Yutaka Hoshino, Tomoko Zama, Susumu Hirao
DOI:10.4103/ijmy.ijmy_111_22  
Background: In August 2018, a male worker (Pt1) in an office was diagnosed with smear-positive pulmonary tuberculosis (TB). This study aims to characterize the cases found in the TB outbreak in the office. Methods: The risks of TB disease or infection were compared among the staff members by seating locations. Results: A total of 116 current and ex-staff members were investigated, among whom 13 patients with active TB, including Pt1, and 20 with latent TB infection were found by the end of 2020. One-third of the seating groups located at one end of the office that Pt1 belonged to had the highest risk of TB disease (30.8%, 95% confidence interval [CI]: 14.3%–51.8%) and infection (61.5%, 95% CI: 40.6%–79.8%) with a high relative risk of TB infection (6.2, 95% CI: 2.0–18.8) compared to another one-third of the seating groups at the other end of the office that had the lowest risk of active TB (0%, 95% CI: 0%–11.6%) and TB infection (10.0%, 95% CI: 2.1%–26.5%). Conclusion: The seating groups that Pt1 belonged to had the highest risk of TB disease and infection because the staff members in the groups were exposed to the air containing TB bacilli from Pt1. Local health offices should initiate active case finding using chest X-rays as soon as they are notified of a sputum smear-positive TB case if the delay of the diagnosis is longer than three months.
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Messenger RNA expression of toll-like receptors (TLR2, TLR4, and TLR9) in HIV-1 infected patients with and without tuberculosis co-infection p. 293
Gaurav Kaushik, Richa Vashishtha
DOI:10.4103/ijmy.ijmy_108_22  
Background: Gene expression levels of TLRs (TLR2, TLR4 and TLR9) are directly involved in the virus recognition and initiation of innate immune responses, therefore, the effect of HIV infection on TLRs gene expression was investigated in functional context through mRNA levels estimations of selected TLRs. Methods: In the present study mRNA gene expression of TLR2, TLR4 and TLR9 has been investigated in HIV+ and HIV+TB patients and compared with healthy subjects. Result: The increase expression of TLR2, TLR4 and TLR9 (mRNA level) relative to the internal gene GAPDH was observed in HIV+ and HIV+TB patients as compared to healthy subjects. Similarly, increase in TLRs mRNA expression was observed in HIV+TB patients as compared to HIV+ patients. Conclusion: A modest increase in expression of TLRs in HIV+ patients with and without TB co-infection suggest a potential role for these TLRs in HIV-1 immunopathogenesis.
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Cytokines dynamics in a wistar rat model infected with Mycobacterium Tuberculosis strain H37Rv p. 299
Bobby Singh, Brian Wasita, Reviono Reviono
DOI:10.4103/ijmy.ijmy_84_22  
Background: The immunology characteristics of the rat model of tuberculosis (TB) infection are still unclear. This study aimed to evaluate the dynamics of pathology and cytokines in a rat model infected with Mycobacterium TB (MTB). Methods: Sixty male Wistar rats were divided into four groups, namely the control group (without MTB infection) and the MTB -induced group (observations at week-3, week-6, and week-12 postinfection). Granuloma formation was analyzed by histology procedure. Analysis of the levels of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), IL-17, IL-2, IL-4, and IL-12 was performed using an enzyme-linked immunosorbent assay technique. Results: The number and size of the ganulomas increased proportionally between weeks 6 and 12 postinfection. Several cytokines, namely IL-6, IL-17, IL-2, IL-4, and IL-12 significantly increased in the 6th week compared to the 3rd week after infection (P < 0.05). These cytokines decreased significantly at the 12th week compared to the 6th week (P < 0.05). TNF-α was found to be stable at the third and 6th weeks and then decreased at the twelfth postinfection week. For IL-12, the longer the infection time, the higher the level. Conclusions: It was concluded that there was a typical pattern of TB infection in Wistar rats, namely certain cytokines that peaked at week 6 of infection. Thus, TB infection in rats can be a model for early-phase TB study.
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Helping map the taxonomical position of the Nontuberculous Mycobacteria (NTM) in cystic fibrosis p. 303
John Edmund Moore, Beverley Cherie Millar
DOI:10.4103/ijmy.ijmy_120_22  
Background: Nontuberculous mycobacteria (NTMs) have now emerged as important opportunistic bacterial pathogens, particularly among patients with cystic fibrosis (CF). The development of improved molecular technologies and bioinformatics and the adoption of whole-genome sequencing to more isolates have allowed for a reanalysis of the existing taxa within the genus Mycobacterium, resulting in the renaming of some existing NTM Mycobacterium species to three novel genera, viz., Mycolicibacterium gen. nov., Mycolicibacter gen. nov. and Mycobacteroides gen. nov. This has resulted in controversy, particularly within the clinical community, accompanied by a reluctance to adopt and employ these new bacterial names. Therefore, the aims of this study were (i) to identify NTM organisms associated with CF lung disease that have been reported previously in the published literature, (ii) to examine the realignment of NTM organisms previously described in CF within the revised new mycobacterial taxonomy and renaming, and (iii) to identify and explore online taxonomical tools to help educate clinical medicine about recent changes in NTM taxonomy. Methods: Three tasks were performed, namely (i) to identify NTM organisms previously associated with people with CF, (ii) to examine the extent and scope of the reclassification of CF-related NTM species affected by changes in recent taxonomy and nomenclature, and (iii) to identify and examine the educational utility of online taxonomical educational tools/software (LifeMap [http://lifemap.univ-lyon1.fr/]; National Center for Biotechnology Information [NCBI] Taxonomy browser [https://www.ncbi.nlm.nih. gov/guide/taxonomy/]; and List of Prokaryotic names with Standing in Nomenclature [LPSN] [https://lpsn.dsmz.de/]). Mycobacterium (Mycobacteroides) abscessus was selected as the species to evaluate the application of these tools. Results: Twenty-one NTM species have been reported that have been associated with CF lung disease. Of these, two have been reclassified into the Mycobacteroides genus, two into the Mycolicibacter genus, and seven into the Mycolicibacterium genus. LifeMap, NCBI Taxonomy browser, and LPSN offered interactive visual support to better understand the taxonomy and nomenclature of NTM organisms. Conclusion: We, therefore, advocate that clinical and scientific parties employ these online tools to gain a better insight into the familiarization and understanding of such evolving NTM classification, thereby aiding a better lexicon and communication among all stakeholders.
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Treatment and management of hypersensitivity reactions developed against anti-tuberculosis drug p. 309
Zeynep Yegin Katran, Ismet Bulut, Aylin Babalik, Metin Keren
DOI:10.4103/ijmy.ijmy_78_22  
Background: The World Health Organization Global Tuberculosis Report 2021 defines tuberculosis as the second infectious disease that causes sickness and death after COVID 19 and ranks it as the 13th among the global causes of death. However, the prevalence of the patients developing a hypersensitivity reaction against antituberculosis treatment is yet unknown. This study aimed to investigate the prevalence of drug allergy against antituberculosis treatment and the management of such a problem. Methods: This is a case–-control study. All patients hospitalized in the tuberculosis inpatient service between February 01, 2015 and May 01, 2021 due to hypersensitivity reaction or who developed hypersensitivity during hospitalization were included in the case group. Patients who received inpatient treatment between the same dates and did not develop any drug allergy were included in the control group. The demographic characteristics of the patients, the tuberculosis diagnostic indicator, the type of hypersensitivity reaction that developed, the duration of the manifestation of the reaction and its treatment were evaluated for the purpose of the study. Results: A total of 2677 patients were hospitalized in the tuberculosis inpatient service between the specified dates. Two hundred and ten patients were consulted for drug hypersensitivity reactions in the Allergy Clinic. The prevalence of drug allergy in inpatients was calculated as 7.8%. One hundred and forty-eight patients examined by the authors were included in the study. Seventy-nine of the 148 patients (53.4%) who developed a hypersensitivity reaction were male, the mean age of these patients was 47.20 ± 18.95 years, 89.2% (n = 132) were citizens of the Republic of Turkey, 7.4% (n = 11) of the patients had received tuberculosis treatment before, 16.9% (25) had developed antituberculosis drug resistance and the bacteriological diagnosis was present in 79.7% (118) of the patients. Chi-square test results applied in the allergy group revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P < 0.001), Turkish citizen patients (P = 0.004), in new cases (P = 0.017), in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The results of the logistic regression analysis performed also revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P = 0.006), Turkish citizen patients (P = 0.023), in new cases (P = 0.017) and in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The success of the treatment was higher in the group that developed a hypersensitivity reaction compared to the control group. About 63.5% (94) of the patients examined developed Type I hypersensitivity reactions, whereas 36.7% (53) of the patients examined developed Type IV hypersensitivity reactions. Type I and Type IV reactions were observed simultaneously in a single patient. Considering the prevalence of developing a hypersensitivity reaction, pyrazinamide was determined as the drug inducing the hypersensitivity reaction in 25 (48.1%) patients. This figure was 15 patients (28.2%) for rifampicin, nine patients (17.3%) for isoniazid, and five patients (9.6%) for ethambutol. As a result, even patients who developed Type I or Type IV reactions were able to complete their antituberculous drug regimens with successful desensitization. Conclusion: The risk of developing an allergic reaction in patients who are administered on antituberculosis treatment is common, particularly in the first 2 months of treatment. However, we believe that the compliance of the patients to the antituberculosis treatment has been improved at the end of appropriate management of hypersensitivity reactions and the treatment results in success.
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Correlation of single-nucleotide polymorphism at interferon-gamma R1 (at Position − 56) in positive purified protein derivative health workers with COVID-19 infection p. 318
Mohammad Varahram, Saeid Besharati, Poopak Farnia, Jalaledin Ghanavi, Shima Saif, Jalal Heshmat Nia, Mohammad Reza Madani, Parissa Farnia, Ali Akbar Velayati
DOI:10.4103/ijmy.ijmy_133_22  
Background: The aim of the present study was to investigate the susceptibility of purified protein derivative (PPD) plus health-care workers to SARS-CoV-2 (COVID-19). For this reason, single-nucleotide polymorphism (SNP) of interferon-gamma (IFN-γ) gene at position +2109 and IFN-γ receptor 1 (R1) at position −56 was assessed in PPD plus group before and after COVID-19 infection (2017–2018; 2020–2021). Methods: The selected study cases (n = 100) that were working in tuberculosis (TB) unite (5–10 years) with PPD positivity >15 mm (16–20 mm) were included in this investigation. Sampling was done twice, once before and after the COVID-19 pandemic. Group A contains 50 samples collected from the GenBank TB laboratory that belong to TB staff before the pandemic (2017–2018). The other sample (Group B; 2021) was collected from the same unite during the COVID-19 pandemic. The SNP in the IFN-γ gene (+2109; 670 bp) and IFN-γ R 1 (−56; 366 bp) was performed using a specific primer and the polymerase chain reaction products were digested using restriction enzyme Fau I and Bts I, respectively. Statistical analyses were used to obtain the frequency of alleles among all studied cases. The confidence intervals (CIs) and t-test were calculated using the SPSS and GraphPad Prism software. Results: In overall, the most frequent genotype in Group A was AA (41/50; 82%) and Group B was 76% (38/50) in position + 2109 (odds ratio [OR] = 0.69, 95% CI, 0.26–1.83, and P = 0.46). Although in position −56, the most frequent genotype in Group A was TT (35/50; 70%) which significantly was than Group B TT (15/50; 30%) (OR = 0.184, 95% CI, 0.78–0.43, and P = 0.00). The frequency of allele A was more in both groups at position + 2109 (OR = 0.815, 95% CI, 0.23–2.86, and P = 0.75), whereas the dominate allele at position −56 was T in Group A (OR = 1.37, 95% CI, 0.62–3.02, and P = 0.42). Conclusion: No significant differences were observed in + 2109 in genotype among Group A and B. The main differences were seen in IFN-γ R1 at position (−56) between Group A and B. Hence, the IFN-γ R1 may play important role in COVID-19 infection. However, more study is needed to clear the IFN-γ correlation to COVID-19 infection.
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CASE REPORTS Top

Image-guided fine-needle aspiration cytology or core biopsy – A key to definitive diagnosis of tuberculous mastitis p. 323
Shirish Sahebrao Chandanwale, Rajeshwari Ravishankar, Anshita Atul Garg, Mayur Ravindrarao Ambekar
DOI:10.4103/ijmy.ijmy_98_22  
Despite advances in the treatment, tuberculosis (TB) is still a global health problem. The diagnosis of extrapulmonary TB in their primary form is very challenging. Breast TB is very uncommon and accounts for < 0.1% of all breast lesions. Due to rarity of the disease and difficulty in diagnosis, we report a case of a 40-year-old female who had a hard lump in the right breast. Full-field digital mammography suggested the lesion as American College of Radiology Breast Imaging Reporting and Data System-5 (ACR BIRADS-5) (highly suggestive of carcinoma). Histopathological examination of multiple cores of the breast tissue showed lymphocytic inflammatory infiltrates confined to breast lobules. Fungal stains and Ziehl–Neelsen (ZN) stain were negative. A diagnosis of chronic mastitis with the possibility of autoimmune lobular mastitis was suggested. Subsequent image-guided fine needle aspiration smears showed epithelioid granulomas mixed with lymphocytes. Areas of amorphous-to-granular eosinophilic material (caseous necrosis) were seen at places. ZN stain showed acid-fast bacilli. A diagnosis of tuberculous mastitis was given.
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Erythema induratum of bazin – Skin lesions with pyrexia of unknown origin undiagnosed for 4 years p. 326
Mansoor C Abdulla
DOI:10.4103/ijmy.ijmy_67_22  
Erythema induratum of Bazin is characterized by chronic, tender, erythematous, indurated subcutaneous nodules on the lower extremities caused by tuberculin hypersensitivity. A 21-year-old woman presented with recurrent episodes of multiple erythematous scaly lesions over both lower limbs below the knee and low-grade fever for 4 years. She was treated from various outside hospitals with multiple courses of antibiotics and nonsteroidal anti-inflammatory drugs without improvement. The histopathology of the skin lesion was suggestive of erythema induratum. She had complete resolution of her skin lesions and fever following 6 months of treatment with antitubercular drugs. A delay in the diagnosis of rare presentations of tuberculosis can result in the administration of ineffective and potentially damaging treatments.
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Multifocal cutaneous tuberculosis coexisting with pulmonary tuberculosis p. 329
Anjali Srikanth Mannava, Chris Alex Wesley Garapati, Satyaki Ganguly, Kranti Chandan Jaykar
DOI:10.4103/ijmy.ijmy_73_22  
Tuberculosis (TB) is caused by Mycobacterium tuberculosis and it can affect multiple organ systems. Cutaneous TB, a less common type of extrapulmonary TB can coexist with TB of other organs. Here, we describe a case of multifocal cutaneous TB suggestive of two different morphological types with concomitant miliary pulmonary TB.
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Dermoscopy and clinicopathology features in diagnosing paucibacillary leprosy: Case series p. 332
R Rusmawardiana, Nyimas Nursyarifah, Fifa Argentina, Raden Pamudji
DOI:10.4103/ijmy.ijmy_113_22  
A wide variety of leprosy clinical manifestations poses an early diagnostic challenge. Currently, various diagnostic modalities have been developed to optimize the definite diagnostic of leprae. Leprosy diagnosis was established based on the presence of either hypopigmented or reddish skin lesions accompanied with loss of sensation, peripheral nerve involvement, and a positive skin-slit smear (SSS) test result for acid-fast bacilli. Resemblance of leprosy skin lesions to excessively many other differential diagnoses, unclear nerve involvement, and negative results of SSS in paucibacillary (PB) leprosy become a diagnostic veil to clinicians. Furthermore, an additional modality for PB leprosy is needed as an important way to prevent misdiagnoses and complications of leprosy. Commonly, a biopsy or polymerase chain reaction examination is performed to exclude other similarly presenting diseases. Dermoscopy examination, the noninvasive technique that allows a better examination to visualize skin lesions, along with clinicopathology features of skin lesions can help to establish the diagnosis of PB leprosy.
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“Tree-in-Bud” appearance in the liver in disseminated tuberculosis p. 337
Harsimran Bhatia, Pankaj Gupta
DOI:10.4103/ijmy.ijmy_82_22  
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COVID-19 coinfection with Mycobacterium abscessus: A note p. 339
Pathum Sookaromdee, Beuy Joob, Viroj Wiwanitkit
DOI:10.4103/ijmy.ijmy_90_22  
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Tumor necrotic factor pathway, monkeypox, and tuberculosis: Correspondence p. 341
Rujittika Mungmunpuntipantip, Viroj Wiwanitkit
DOI:10.4103/ijmy.ijmy_129_22  
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