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   Table of Contents - Current issue
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October-December 2022
Volume 11 | Issue 4
Page Nos. 343-474

Online since Saturday, December 10, 2022

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REVIEW ARTICLES  

Antibiotic resistance acquisition versus primary transmission in the presentation of extensively drug-resistant tuberculosis p. 343
Ronan Francis O’Toole
DOI:10.4103/ijmy.ijmy_187_22  
Mycobacterium tuberculosis is the leading cause of mortality worldwide due to a single bacterial pathogen. Of concern is the negative impact that the COVID-19 pandemic has had on the control of tuberculosis (TB) including drug-resistant forms of the disease. Antimicrobial resistance increases the likelihood of worsened outcomes in TB patients including treatment failure and death. Multidrug-resistant (MDR) strains, resistant to first-line drugs isoniazid and rifampin, and extensively drug-resistant (XDR) strains with further resistance to second-line drugs (SLD), threaten control programs designed to lower TB incidence and end the disease as a public health challenge by 2030, in accordance with UN Sustainable Development Goals. Tackling TB requires an understanding of the pathways through which drug resistance emerges. Here, the roles of acquired resistance mutation, and primary transmission, are examined with regard to XDR-TB. It is apparent that XDR-TB can emerge from MDR-TB through a small number of additional resistance mutations that occur in patients undergoing drug treatment. Rapid detection of resistance, to first-line drugs and SLD, at the initiation of and during treatment, and prompt adjustment of regimens are required to ensure treatment success in these patients. Primary transmission is predicted to make an increasing contribution to the XDR-TB caseload in the future. Much work is required to improve the implementation of the World Health Organization-recommended infection control practices and block onward transmission of XDR-TB patients to contacts including health-care workers. Finally, limiting background resistance to fluoroquinolones in pre-XDR strains of M. tuberculosis will necessitate better antimicrobial stewardship in the broader use of this drug class.
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Scoping review: QT interval prolongation in regimen containing bedaquiline and delamanid in patients with drug-resistant tuberculosis Highly accessed article p. 349
Oki Nugraha Putra, Yulistiani Yulistiani, Soedarsono Soedarsono
DOI:10.4103/ijmy.ijmy_178_22  
Background: A regimen containing bedaquiline–delamanid is recommended in management of drug-resistant tuberculosis (DR TB) to increase a success rate. However, this regimen was rare in a clinical setting due to a potential risk of QT prolongation. Several studies have reported the incidence of QT prolongation after administration of this regimen, but the results are inconsistent due to different sample size, study design, and covariate. The aim of this review is to summarize and analyze the published articles related to QT prolongation of bedaquiline and delamanid in PubMed and ScienceDirect databases using a scoping review. Methods: This scoping review was conducted under PRISMA for scoping review. The outcomes of this review were incidence of QT prolongation and death. We found 8 articles to be included in this review. Results: The incidence of QT prolongation was higher for DR TB patients who received a regimen containing bedaquiline and delamanid. However, this review found no clinical symptoms, such as cardiac arrhythmias, torsade de pointes, or even death. DR TB patients, especially the elderly, were at risk for QT prolongation. Special consideration in patients with HIV and low level of potassium should be closely monitored for QT interval. Conclusion: The regular measurement of electrocardiography was highly recommended to evaluate QT interval. Generally, the use of individualized regimen containing bedaquiline and delamanid is relatively safe in DR TB patients.
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ORIGINAL ARTICLES Top

Risk factors associated to multidrug-resistant tuberculosis in patients attending the deido district hospital of Douala – Cameroon p. 356
Djuikoue I Cecile, Ndjip Ndjock S. Alex, Nzenya D Joëlle, Nana S Cedric, Chounna T Noemy, Wandji G Irene, Mfongouot P Leila, Ketchaji Alice, Nguedia Assob J. Clement, Pokam Thumamo D. Benjamin
DOI:10.4103/ijmy.ijmy_136_22  
Background: Multidrug-resistant tuberculosis (MDR-TB) is defined as resistance to at least isoniazid and rifampicin. In Cameroon, the prevalence is estimated at 150 cases/100,000 inhabitants or 6000 cases out of an estimated population of 3 million. Objective: The aim of the present study was to determine the risk factors associated with MDR-TB at Deido District Hospital located in the littoral region of Cameroon. Methods: This was a cross-sectional and analytical retrospective study. Our sample included all TB patients undergoing treatment at the Diagnostic and Treatment Center of the hospital from January 2019 to August 2020. Identified risk factors of MDR-TB were analyzed using the SPSS software version 20.0. Results: A total of 304 participants were enrolled with a predominance of 185 (60.8%) men. The average age was 35 years (29–43 years). About 122/304 (40%) of the patients suffered from MDR-TB. The significant factors associated with MDR-TB were occupation (adjusted odd ratio [aOR] = 61.46), monthly income (aOR = 0.11), history of TB (aOR = 5.3), alcohol consumption (aOR = 12.7); self-medication (aOR = 5.4) and consultation of traditional healers for any cure (aOR = 155.84). Conclusion: The emergence of MDR-TB associated with several risk factors in the study area is worrisome and can be prevented by improving the living conditions of patients and putting in place appropriate treatment strategies.
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Tuberculin test versus interferon gamma release assay in pregnant women with household contacts of tuberculosis patients p. 364
Maisuri Tadjuddin Chalid, Dian Puspawaty, Andi Mardiah Tahir, Hidayah Najdah, Muhammad Nasrum Massi
DOI:10.4103/ijmy.ijmy_112_22  
Background: Pregnant women who live in tuberculosis (TB)-affected households are more likely to develop latent TB infection (LTBI), which often escapes treatment. This study aims to determine if Interferon-gamma release (IGRA) is reliable in screening for LTBI in pregnant women, compare to the tuberculin skin test (TST). Methods: It was a cross-sectional study that involved 60 pregnant women with TB contact history as a proxy for LTBI and 30 pregnant women without contact history. Latent TB was detected using the TST 5 tuberculin units and IGRA using the QuantiFERON Gold Plus TB Test kit (QFT-Plus). The sensitivity and specificity of the two diagnostic methods and the agreement between them were estimated using SPSS version 20.0. Results: The sensitivity 95% (95% confidence interval [CI]: 86.08%–98.96%) and specificity 26.7% (95% CI: 12.28%–45.89%) of TST were compared to that of the IGRA with 60% (95% CI: 46.54%–72.44%) and 73.3% (95% CI: 54.11%–87.72%) sensitivity and specificity, respectively in detecting LTBI in pregnancy. Although there was a significant difference (P < 0.05) between TST and IGRA, the agreement was fair (kappa 0.39; 95% CI: 0.24–0.45). Conclusion: TST assay is more sensitive than IGRA; however, the specificity of IGRA was superior to the TST method. In this study, a fair agreement of TST and IGRA was observed for detecting latent TB infection in pregnant women with household contact with TB patients.
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Standardization of a stool concentration method for Mycobacterium tuberculosis detection in the pediatric population p. 371
Priya Rajendran, Baskaran Murugesan, Sarath Balaji, Sivakumar Shanmugam, Sivaraman Palanisamy, Thirumalani Ramamoorthy, Sindhu Hasini, Bella Devaleenal, Basilea Watson
DOI:10.4103/ijmy.ijmy_126_22  
Background: The inability of young children to expectorate sputum and paucibacillary status of Mycobacterium tuberculosis (MTB) increases its diagnostic complexity. In this study, we aimed to standardize a stool concentration method for the detection of MTB and its drug resistance by line probe assay (LPA). Methods: The stool from 10 healthy children spiked with H37Rv in five different dilutions (1:1, 1:10, 1:100, 1:1000, and 1:10,000), and stool from 10 confirmed TB and 54 clinically diagnosed TB children were subjected to an in-house stool concentration protocol. All the processed filtrates were subjected to smear microscopy, solid culture, Xpert ultra testing, and LPA. Results: Of 10 control samples, growth was seen in four samples (neat 1:1). In smear microscopy, bacilli could be seen in eight samples (1:1 and 1:10). Xpert ultra testing could detect MTB in eight samples in all dilutions with different loads. LPA could detect MTB in all samples and dilutions. In microbiologically confirmed children, seven out of 10 stool samples tested were positive. Out of 54 children with clinically diagnosed TB, 4 (7.4%) could be confirmed by microbiological diagnosis. Conclusion: The protocol standardized in this study proves to be better working in the molecular detection of MTB.
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Culture filtrate protein 32 as a potential target to attenuate the heterogeneous antibody response against Mycobacterium tuberculosis Antigens in different endemic settings p. 378
Chaouki Benabdessalem, Rym Ouni, Wafa Ben Hamouda, Jihene Bettaieb, Dahmani Mohamed Fathallah, Mohamed-Ridha Barbouche
DOI:10.4103/ijmy.ijmy_127_22  
Background: We previously reported the development of an enzyme-linked immunosorbent assay for the detection of the immunoglobulin G (IgG) response to Mycobacterium tuberculosis virulence factor – culture filtrate protein 32 (CFP32). The assay achieved high performance in comparing healthy Bacillus Calmette–Guerin-vaccinated controls with active tuberculosis (TB) patients from the Tunisian population. Herein, we aimed to assess the anti-CFP32 IgG response in suspected or confirmed active pulmonary TB individuals in different endemic settings. Methods: Serum samples were obtained from 224 donors from African and Latin American countries with variable levels of TB endemicity and different ethnical origins. Receiver operating characteristic curve was used to evaluate the performance of the serological assay. Results: The area under the curve was 0.70. The use of a cutoff level of 0.65 gave 67% and 68% sensitivity and specificity, respectively, regardless of ethnicity and endemicity. Except for the suspected Latin American group, overall multiple comparisons of medians pointed out the stability of the anti-CFP32 IgG response across the different endemic settings. Therefore, endemicity and ethnicity seem not to affect anti-CFP32 IgG response, mainly for detecting confirmed active TB individuals. Conclusions: These findings suggest that the inclusion of CFP32 epitopes in multi-antigen TB assay could attenuate serological differences related to heterogeneous endemicity and ethnicity. For this purpose, we further identified B-cell epitopes belonging to CFP32 by an in silico analysis.
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Comparative evaluation of interleukin-10, transforming growth factor-β, and interleukin-17 in gastrointestinal tuberculosis and crohn's disease p. 384
Anjali Gupta, Kusum Sharma, Vishal Sharma, Jagdeep Singh, Ritambhra Nada, Biman Saikia, Ranjana W Minz, Shashi Anand, Mahendra Kumar
DOI:10.4103/ijmy.ijmy_131_22  
Background: Gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) are close mimickers and difficult to discriminate. Recent work has focused on the immunological differences between GITB and CD based on cytokines related to T-regulatory cells and Th17 cells. In the present cross-sectional study, suspected cases of GITB or CD underwent extensive clinical, radiological, endoscopic, histological, and microbiological assessment. The diagnosis was based on standard criteria and response to antitubercular therapy endoscopically. Methods: Interleukin (IL)-10, transforming growth factor-β (TGF-β), and IL-17 were measured and compared between GITB and CD along with other parameters. Fisher's exact test and Mann–Whitney U test were used as per the data type. Results: Of the 27 patients, 11 had CD, 9 had GITB, and 7 had other conditions. Chronic diarrhea, involvement of left and long segments of the colon, and aphthous ulcers were significantly more frequent in CD; however, transverse ulcers were in GITB. IL-10 was reduced in both GITB (median-interquartile range [IQR] 9.54 [3.65–24.04]) and CD (median-IQR 13.28 [6.91–22.50]) compared to control (median-IQR 26.72 [10.34–35.43]). TGF-β showed little variation, but IL-17 was below the detection limit in most cases. None of these cytokines were significantly different between CD and GITB. The sensitivity and specificity of multiplex Mycobacterium tuberculosis-polymerase chain reaction were 44.44% and 100%, respectively. Conclusion: Serum cytokine profiling (IL-10, IL-17, and TGF-β) could not significantly differentiate GITB and CD. Moreover, extensive molecular, transcriptomic, chemokines, and cytokine analyses may shed light on these aspects.
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Bibliometric analyses of applications of artificial intelligence on tuberculosis p. 389
Miguel Cabanillas-Lazo, Carlos Quispe-Vicuña, Milagros Pascual-Guevara, John Barja-Ore, Maria Eugenia Guerrero, Arnaldo Munive-Degregori, Frank Mayta-Tovalino
DOI:10.4103/ijmy.ijmy_134_22  
Background: Tuberculosis is one of the leading causes of death worldwide affecting mainly low- and middle-income countries. Therefore, the objective is to analyze the bibliometric characteristics of the application of artificial intelligence (AI) in tuberculosis in Scopus. Methods: A bibliometric study, the Scopus database was used using a search strategy composed of controlled and free terms regarding tuberculosis and AI. The search fields “TITLE,” “ABSTRACT,” and “AUTHKEY” were used to find the terms. The collected data were analyzed with Scival software. Bibliometric data were described through the figures and tables summarized by absolute values and percentages. Results: Thousand and forty-one documents were collected and analyzed. Yudong Zhang was the author with the highest scientific production; however, K. C. Santosh had the greatest impact. Anna University (India) was the institution with the highest number of published papers. Most papers were published in the first quartile. The United States led the scientific production. Articles with international collaboration had the highest impact. Conclusion: Articles related to tuberculosis and AI are mostly published in first quartile journals, which would reflect the need and interest worldwide. Although countries with a high incidence of new cases of tuberculosis are among the most productive, those with the highest reported drug resistance need greater support and collaboration.
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A prospective study of the clinical profile of hemoptysis and its correlation with radiological and microbiological findings p. 394
Harveen Kaur, Naveen Pandhi, NC Kajal
DOI:10.4103/ijmy.ijmy_137_22  
Background: The etiological pattern of hemoptysis has evolved, with pulmonary tuberculosis (PTB) becoming less prevalent as a cause. There is a paucity of literature regarding the spectrum of diseases that present as hemoptysis and the data related to detailed clinical profile are lacking. Hence, this study is taken up to determine the clinical profile of hemoptysis and its correlation with radiological and microbiological findings. Methods: This was a 3-year observational prospective study of a total of 50 patients who presented with active hemoptysis. Data were recorded from these patients for assessing the clinical characteristics, radiological, and microbiological correlation. Results: The most common etiologies of hemoptysis identified in this study were PTB in 60% of the patients, aspergilloma in 14%, followed by bronchiectasis in 8%, pneumonia in 8%, carcinoma lung in 4%, and lung abscess in 1 (2%). Mild hemoptysis was present in 8% of patients, whereas 42% had moderate hemoptysis, 18% of patients had severe, and 32% had massive hemoptysis. Sixty percent of patients had recurrent hemoptysis, and the majority of the patients, i.e., 68% tested negative on sputum smear examination for acid-fast bacillus. In 60% of patients, no growth was obtained in the sputum cultures. The most common organisms isolated from sputum cultures of the rest of the patients were Pseudomonas in 14%, Klebsiella in 10%, Escherichia coli in 4%, Staphylococci in 4%, and Streptococcus pneumoniae in 4% of the cases. The majority of the patients were having consolidation and cavitary disease. A highly significant correlation was noted between the radiological findings of consolidation, mycetoma, cystic shadows, lung mass, and lung abscess and the etiology of hemoptysis (P = 0.000). Conclusion: Hemoptysis of any volume implies a life-threatening process, which mandates immediate evaluation and treatment. It is evident that the etiological spectrum of hemoptysis is continuously changing, and more sophisticated investigations, better imaging techniques, bronchoscopic tools, availability of newer techniques in the developing world, and changing patterns of diseases, all contribute to these changes. Identification of the etiology, and localization of the bleeding site, is essential for the efficient management of hemoptysis.
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Pulmonary tuberculosis and diabetes mellitus: Clinical profile and outcomes p. 400
John Titus George, Angel T Miraclin, Sowmya Sathyendra, Joy Sarojini Michael, Jasmin Prasad, Grace Rebekah
DOI:10.4103/ijmy.ijmy_154_22  
Background: India is endemic for Tuberculosis (TB), contributing to the world's highest number of active cases. Diabetes (DM), with its increasing burden in India, could contribute to adverse outcomes among patients with TB. Methods: Consecutive patients with sputum smear positive pulmonary tuberculosis were included in the study. We defined cases as those patients with diabetes at recruitment. Controls were non diabetics (NDM). Sputum samples for AFB smears, AFB culture and Xpert PCR along with blood samples for glycosylated Haemoglobin and glucose levels were collected at recruitment and at 6 months from patients with sputum positive pulmonary TB. Blood glucose levels and sputum smears were repeated at 2 months and monthly till they tested negative. The primary outcome studied was mortality at 6 month follow-up. The secondary outcomes included the time to conversion of sputum smears and cure rates between cases and controls. Results: We recruited 124 patients of which 68 were cases. Mortality after therapy was 15% in cases and 7% in controls, however, the difference was not statistically significant. Equal proportions in each group (Diabetics: 9% vs. NDM 9%) had persistent smear positivity at 2 months. There was no association between delayed sputum conversion and uncontrolled diabetes. Only about 57% of cases and 50% of controls were documented to have completed treatment or been cured. A significant reduction in HbA1c after 6 months of Antituberculous therapy was noted among the cases. [Mean difference – 1.76, P-value – 0.001, 95% CI of difference – (1.01 – 2.52)]. Conclusions: Diabetes did not have adverse outcomes in the form of increased mortality or delayed sputum conversion rates. The high proportion of loss to follow-up seems to be a trend of concern, which should be addressed emergently.
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Middlebrook 7h11 reduces invalid results and turnaround time of phenotypic drug-susceptibility testing of M. tuberculosis p. 407
Praharshinie Rupasinghe, Jens Vereecken, Pieter Graulus, Tom Decroo, Elisa Ardizzoni, Cathy Hewison, Dimitri Donchuk, Helena Huerga, Anita Mesic, Leen Rigouts, Bouke C de Jong
DOI:10.4103/ijmy.ijmy_159_22  
Background: Phenotypic drug-susceptibility testing (pDST), which relies on growth inhibition in the drug-containing media, remains a challenge for fastidious Mycobacterium tuberculosis complex (MTBc) isolates due to insufficient growth on the growth controls (GC). Middlebrook 7H11 (M7H11) medium contains casein hydrolysate, which may favor the growth of such strains. Method: In this study, we tested whether M7H11 reduces invalid results due to insufficient growth on the GCs and the turnaround time (TAT) of pDST for MTBc compared to Middlebrook 7H10 (M7H10) without affecting the accuracy of the pDST results and how it differs between rifampicin- and isoniazid-susceptible non multi-drug resistant (non-MDR), MDR and MDR with additional resistance to fluoroquinolones (Pre-XDR) MTBc isolates. We compared the proportions of invalid pDST results due to lack of growth on the GCs, TATs of valid parallel drug-susceptibility testings as an indicator of speed of MTBc growth, and colony-forming unit (CFU) count on the most diluted GC of the parallel pDSTs after equal incubation periods as an indicator of growth abundance on M7H11 and M7H10. We also analyzed the agreement between the pDST results of the same drug or drugs in the same drug class, tested in parallel on both media. Results: For MDR and pre-XDR isolates, relative to M7H10, M7H11 significantly reduced the occurrence of invalid pDST results due to insufficient growth on the GCs (odds ratio [OR] = ∞ [95% confidence interval (CI) 1.9–∞], P = 0.004 for MDR, OR = ∞ [95% CI 3.3–∞], P = 0.0001 for pre-XDR) and the TAT of pDSTs (OR = 17 [95% CI 2.6–710.4], P = 0.0001 for MDR, OR = 9.3 [95% CI 4.0–26.5], P < 0.0001 for pre-XDR). The growth abundance of MTBc on M7H11 was significantly higher compared to M7H10 (17 CFU on M7H10 vs. 28 on M7H11), irrespective of drug-resistance profiles. The agreement between the pDST results between the two media was high (Cohen's k > 0.98). Conclusion: Our study findings suggest that M7H11 is preferred over M7H10 for pDSTs of MTBc isolates.
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Evaluation of the resistance of Mycobacterium tuberculosis to rifampicin at the regional hospital center of Maradi, Niger Republic p. 412
Ousmane Abdoulaye, Iklima Daibou Idi, Harouna Amadou Mahaman Laouali, Ibrahim Maman Lawan, Hassane Boureima, Fatima Guiet Mati, Ahamadou Biraima, Boukar Sidi Maman Bacha, Saadou Habou Mamane, Amoussa Gazaliou Issa
DOI:10.4103/ijmy.ijmy_160_22  
Background: According to the World Health Organization (WHO) data, 600,000 cases of rifampicin-resistant tuberculosis (TB) have been reported worldwide, including 490,000 cases of multidrug-resistant TB. Thus, through the present study, we proposed to evaluate the resistance of Mycobacterium tuberculosis to rifampicin in the regional hospital of Maradi. Methods: Our study involved 887 sputum samples that were GeneXpert tested from January 2016 to December 2020. These data were collected from the laboratory records of the Maradi Regional Hospital and analyzed with SPSS and Excel 2013 software. Results: In total, more than half of the patients were male, i.e., a sex ratio of 3.03. The average age was 41 years. The rate of detection of M. tuberculosis by GeneXpert was 42% and the frequency of resistance to rifampicin was 20%. However, treatment failure and relapse were associated with this monoresistance in 53.95% and 30.26% of cases, respectively. Conclusion: The present study shows a fairly high prevalence of rifampicin resistance in the Maradi region, corresponding to twice the WHO threshold. The vast majority of these cases presented either a therapeutic failure or a relapse. Urgent and effective actions must be taken to significantly reduce the rates of treatment failure and relapse to decrease the rate of monoresistance and thus avoid the emergence of multidrug-resistant strains.
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Effect of COVID-19 pandemic on incidence of mycobacterial diseases among suspected tuberculosis pulmonary patients in Tehran, Iran p. 415
Jafar Aghajani, Poopak Farnia, Parissa Farnia, Jalaledin Ghanavi, Shima Saif, Majid Marjani, Payam Tabarsi, Afshin Moniri, Zahra Abtahian, Sven Hoffner, Ali Akbar Velayati
DOI:10.4103/ijmy.ijmy_167_22  
Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018–December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein–Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018–2019 and 5220 specimens (30.8%; from 2175 patients) in 2020–2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.
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Novel and rare species of nontuberculous mycobacteria by Hsp-65 gene sequencing p. 423
Rajashekhar Kadasu, Vijay Dharma Teja, Neelima Angaali, Madhusudhan Appa Rao Patil, GK Paramjyothi, K Bhaskar
DOI:10.4103/ijmy.ijmy_175_22  
Background: Nontuberculosis mycobacterium (NTM) is the emerging group of organisms being recognized as etiological agents for diverse clinical conditions such as lymphadenitis, cutaneous, and pulmonary or disseminated lesions. Diverse background patients can acquire these infections such as immunocompetent, immunocompromised patients, or postoperative settings. Rapid addition of newer strains to this group necessitates heightened suspicion in the clinical settings. Specific requirements for cultures, biochemical testing, and molecular methods are needed to diagnose these organisms. Methods: The prospective study conducted at Nizam's Institute of Medical Sciences from January 2019 to December 2021 using various clinical samples using molecular techniques such as line probe assay and hsp-65 gene sequencing to discover new NTM species. The management is challenging since it requires prolonged treatment, multiple drugs, drug resistance, and individualization of treatment in the combination of surgery if needed. In this article, we describe three different NTM species which were not reported in India and highlight to consider these organisms in adequate clinical situation. Results: Mycobacterium iranicum is a rare strain with quick growth and scotochromogenic colonies that are orange-colored. Eight distinct strains were discovered in clinical samples from six different countries: Two each from Iran, Italy, Greece, the Netherlands, Sweden, and the United States. Two of the strains were recovered from cerebrospinal fluid, which is unusual. Mycobacterium species AW6 is an unidentified and unclassified Mycobacterium according to NCBI taxonomy. Mycobacteria malmoense has been linked to lymphadenitis, notably cervical adenitis in children, and pulmonary infection in the majority of cases. Using Line Probe Assay and hsp-65 gene sequencing, novel and uncommon species of NTM were detected from a clinical samples, including sputum and tissue. Conclusion: We report three unusual species of NTMs: M. iranicum, M. species-AW6, and M. malmoense for the first time in India. Novel and rare emerging species of NTMs need to be considered in diverse clinical situations for appropriate therapy and good clinical outcomes.
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Line probe assay test in new cases of tuberculosis with rifampicin resistance not detected by Xpert MTB/RIF p. 429
Soedarsono Soedarsono, Ni Made Mertaniasih, Helmia Hasan, Tutik Kusmiati, Ariani Permatasari, Deby Kusumaningrum, Whendy Wijaksono
DOI:10.4103/ijmy.ijmy_176_22  
Background: In Indonesia, the National guideline for tuberculosis only recommended taking the DST to check INH resistance only for re-treatment cases of rifampicin-susceptible TB (RS-TB) detected by Xpert MTB/RIF. This study was conducted mainly to evaluate the proportion of isoniazid resistance in new cases of RS-TB according to the Xpert MTB/RIF. Methods: This was an observational descriptive study in RS-TB new patients diagnosed by Xpert MTB/RIF. Sputum samples were examined using first-line LPA and evaluated by culture-based DST. Results of first-line LPA and culture-based DST were compared and presented. Results: Fifty-four new cases of RS-TB (according Xpert MTB/RIF) were enrolled in this study. INH resistance was detected in 4 (7.4%) using FL-LPA and in 5 (9.3%) using culture-based DST. RIF resistance was also found in 1 (1.9%) using FL-LPA and in 2 (3.7%) using culture-based DST. Ethambutol resistance was also detected in 4 (7.4%) using culture-based DST. Conclusion: First-line LPA successfully revealed 4 (7.4%) of Hr-TB in new RS-TB cases detected by the Xpert MTB/RIF. In new cases with RS-TB detected by the Xpert MTB/RIF, FL- LPA can be used as rapid molecular DST to detect RIF and INH resistance followed by culture-based DST to examine other drug resistance.
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Evaluation of xpert Mycobacterium tuberculosis rifampicin for tuberculosis diagnosis in a reference laboratory p. 435
Naiara Cristina Ule Belotti, Naiady Konno Madela, Susilene Maria Tonelli Nardi, Daniele Cristina Mariano, Nilza Gomes de Souza, Rosangela Siqueira Oliveira, Heloisa da Silveira Paro Pedro
DOI:10.4103/ijmy.ijmy_195_22  
Background: The Xpert Mycobacterium tuberculosis Rifampicin (MTB-RIF) is a technological innovation that presents precision and speed in the diagnosis of tuberculosis (TB). The study aimed to evaluate the performance of Xpert MTB/RIF in the TB diagnosis and compare its results with those of culture, species identification, Antimicrobial Susceptibility Testing (AST), and rpoB gene sequencing of discordant results in AST, used for the diagnosis of TB in a reference laboratory. Methods: Cross-sectional descriptive study of pulmonary and extrapulmonary samples requesting Xpert MTB/RIF and culture for TB diagnosis from 2015 to 2019 at Adolfo Lutz Institute-São Paulo/Brazil. The analysis was performed with Epi-Info 7.2.1, presenting the distribution of frequencies and, for comparative analyses, Pearson's Chi-square test and Fisher's exact test were used, considering P ≤ 0.05 as statistically significant. For variables agreement, the Kappa method was used. Results: A total of 1575 pulmonary and extrapulmonary samples were analyzed using Xpert MTB/RIF and culture, of which 293 were positive for the MTB Complex in both methodologies with a sensitivity of 94.55%; specificity of 95.97%; accuracy 95.69%; positive predictive value 85.53%; negative predictive value 98.59%, substantial agreement by Kappa 0.87, and detection sensitivity even at lower levels of bacillary load (P < 0.05). The Xpert MTB/RIF and AST showed concordant results (P < 0.05). Conclusion: The study brings forward that the Xpert MTB/RIF shows substantial agreement with the results of culture and AST, contributing to the diagnosis of TB and the rapid detection of resistance. The sequencing of resistant cultures in Xpert MTB/RIF and sensitivity in AST identified the H526N mutation, characterized by a low level of resistance to RIF.
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Outcomes of latent tuberculosis infection treatment in Istanbul p. 442
Abdullah Emre Güner, Sule Kiziltas, Aylin Babalik, Esra Sahin, Al Sibel, Mine Safak, Zeki Kiliçaslan
DOI:10.4103/ijmy.ijmy_196_22  
Background and Aim: Increasing the extensity of latent tuberculosis infection (LTBI) treatment which is one of the important parameters of tuberculosis (TB) control and completing the treatment in success are important. The purpose of this study is to evaluate LTBI treatment indications and treatment outcomes of patients who received LTBI treatment in İstanbul between 2016 and 2018. Methods: The treatment outcomes of people who started LTBI treatment registered in TB dispensaries in Istanbul between 2016 and 2018 were analyzed retrospectively according to the variables of the age groups, gender, dispensary subgroups, and prevention treatment indications. Data collected from the health institutions were evaluated. Results: 26.920 patients received LTBI treatment in all Istanbul TB dispensaries between 2016 and 2018. The evaluation of LTBI treatment indications; contact 15.696, Tuberculin skin test (TST) positivity 2224, immunosuppression 8746, TST conversion 58, sequelae lesion 15, and other indications are identified as 181. The groups which diagnosed with TB disease, mortality, transfer, other, and still in treatment are excluded from the analysis of LTBI treatment outcomes. A total of 25.253 patients were analyzed. 65 percent of the patients had completed LTBI treatment. Variables effective for treatment outcomes are analyzed with logistic regression. Treatment discontinuation was statistically significantly lower in 2017 (odds ratio [OR]: 0.906 confidence interval [CI] [95%] [0.849–0.968]) and 2018 (OR: 0.635 CI [95%] [0.594–0.679]) compared to 2016. Treatment lost to follow-up was statistically significantly lower in those receiving LTBI treatment with the indication of tuberculin skin test positivity (OR: 0.541 CI [95%] [0.487–0.600]) and the indication of immunosuppression (OR: 0.284 CI [95%] [0.142–0.569]) compared to those who received LTBI treatment due to contact. When the treatment results are evaluated according to the TB incidence of the region where the dispensaries are located, treatment lost to follow-up was higher in 101–200 per 100,000 incidence group (OR: 1.201 CI [95%] [1.123–1.285]) and incidence of 201–370 per 100,000 (OR: 1.461 CI [95%] [1.358–1.572]). Treatment lost to follow-up was higher in dispensaries on the European side (OR: 1.293 CI [95%] [1.203–1389]) and the 0–35 age group (OR: 1.248 CI [95%] [1.168–1.333]). Conclusion: In conclusion, the treatment completion rate should be improved for an effective LTBI treatment which is one of the important parameters of targeted TB elimination. Particularly people under the age of 35 years and regions with high-TB incidence should receive special care and close follow-up.
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CASE SERIES Top

A rare case series of HIV-negative patients with early relapsing cervical tuberculosis lymphadenitis p. 448
Hulya Abali, Mediha Gönenc Ortakoylu
DOI:10.4103/ijmy.ijmy_165_22  
Most patients with early recurrent tuberculous lymphadenitis (RTL) can be overlooked due to the paucibacillary character of Mycobacterium tuberculosis complex (MTBC) causing difficulty in the differential diagnosis. Here, we present three cases with early RTL that occurred after completing pulmonary tuberculosis (TB) therapy with a cure, and that improved by early diagnosis and therapy. A 30-year-old migrant male, HIV-negative patient, who had used immunosuppressive drugs for Crohn's disease presented to the TB outpatient clinic with a new anterior cervical lymph node enlargement. Two months ago, his therapy for pulmonary TB and intra-abdominal tuberculous lymphadenitis (TL) was completed. Real-time polymerase chain reaction (RT-PCR) of purulent fine-needle aspiration (FNA) specimen from the anterior cervical lymphadenopathy (LAP) was detected positive for MTBC. Isoniazid (H) resistance was determined via the Seegene system. The 6 cm anterior cervical LAP regressed to a 1.6 cm LAP at the 4th month of initial therapy with first-line antitubercular drugs. A 25-year-old female, the HIV-negative patient, was admitted to the TB outpatient clinic with a bulge on the submandibular area 3 months after the cessation of pulmonary multidrug-resistance TB therapy lasting 2 years. She had an index case but no comorbidity. The cytomorphology of FNA biopsy from the submandibular LAP reported granuloma with necrosis. RT-PCR of the purulent FNA specimen was positive for MTBC. H and rifampicin (R) resistances were found via the Seegene system. The right submandibular 2.9 cm LAP improved to a 1.7 cm LAP 6 months after the initiation of second-line antitubercular therapy. A 19-year-old male, the HIV-negative patient, presented to the TB outpatient clinic with a new bulge on the left supraclavicular area 9 months after cessation of pulmonary TB. He had no comorbidity and index case. RT-PCR of the purulent FNA specimen was positive for MTBC. H and R sensitivities were determined via the Seegene system. After the initial therapy with first-line antitubercular drugs for 2 months, the 1.5 cm left supraclavicular LAP improved to a 1.2 cm LAP.
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CASE REPORTS Top

Reactivation of tuberculosis in patient treated with the antifibrotic drug nintedanib p. 454
Iliya Iliev Krachunov, Yavor Yordanov Ivanov
DOI:10.4103/ijmy.ijmy_194_22  
The novel antifibrotic drugs for idiopathic pulmonary fibrosis give us an opportunity for change the course of the disease. Their usages are expected to rise with the widening of their indications. We report a case of a patient who complains of fatigue breathlessness on exertion, dry cough, and fever up to 38°C while on the antifibrotic drug nintedanib treatment. We proved the reactivation of latent tuberculosis (TB) by microbiology of bronchial lavage. The outpatient died from massive hemoptysis. To our knowledge, we present the first case in the world for reactivation of TB in a patient on treatment with nintedanib. We suggest closer follow-up for patients with a history of TB or living in countries with higher TB prevalence during treatment with antifibrotic drugs.
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A masquerade: An uncommon presentation of a dual infection of leprosy and human immunodeficiency virus p. 457
Varsha Rajat Bhatt, Abhishek Arvind Zanwar, Aditi Mahesh Patel, Mounika Sai Adapa
DOI:10.4103/ijmy.ijmy_188_22  
Leprosy and human immunodeficiency virus (HIV) often mimic clinical features of connective tissue disease (CTD). They can present such as lupus, rheumatoid arthritis, scleroderma, or overlap syndromes and it sometimes creates confusion about the diagnosis. Serology may not be enough to differentiate the two and effective tissue biopsies are often the answer. We report the case of a 38-year-old female, who presented clinically with features of multisystem involvement suspected to be CTD, but was found to have dual infection: HIV and borderline tuberculoid leprosy.
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Coexistence of human immunodeficiency virus, active pulmonary tuberculosis, and aspergilloma: A rare entity p. 460
Sneha Leo, Ravindrachari Mulkoju, Manju Rajaram, Bheemanathi Hanuman Srinivas
DOI:10.4103/ijmy.ijmy_164_22  
Tuberculosis (TB) constitutes a significant burden of infectious diseases worldwide. TB and human immunodeficiency virus (HIV) coinfection potentiate each other, which has a negative impact on the disease progression. Aspergillus colonizing a preexisting parenchymal tubercular cavity is referred to as aspergilloma. Aspergilloma occurring in a patient with active TB is unusual. We report the case of a 50-year-old male who presented to us with complaints of cough and recurrent hemoptysis for 3 months. Clinical and radiological examination revealed right upper lobe aspergilloma. A right upper lobectomy was done and a histopathological examination showed evidence of active TB. The patient was started on antitubercular therapy (ATT) followed by antiretroviral therapy (ART). The presence of active TB should not be overlooked in a patient with aspergilloma, especially in immune-compromised individuals such as people living with HIV, as definitive treatment with surgical resection, and ATT along with ART has better outcomes.
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A tale of three in symbiosis: TB–COVID-19–Bordetella coinfection p. 463
Ravindra Chari Mulkoju, Venkateshwarlu Rajuri, Sneha Leo, Raghava Reddy Kolan
DOI:10.4103/ijmy.ijmy_166_22  
Coinfections/mixed infections are common in the respiratory tract. Many times existing organisms have similar risk factors and clinical features that make the diagnosis difficult. Coronavirus diagnosed in 2019 (COVID-19) and tuberculosis (TB) are two such diseases. Patients with TB have lower cellular immunity and impaired pulmonary function. In such environment, atypical organisms, can infect and make the outcome unfavorable. A 21-year-old malnourished (body mass index- 15 kg/m2) girl presented with fever and cough for 10 days. Sputum for Cartridge Based Nucleic Acid Amplification Test demonstrated Mycobacterium tuberculosis with no rifampin resistance. Fever persisted (100–101°F) and saturation was dropping even after 10 days of antitubercular treatment. A repeat reverse transcription–polymerase chain reaction was done and was positive. In view of persistent symptoms after 20 days, bronchoscopy was done, and cultures showed Bordetella bronchiseptica. Fever and symptoms resolved completely after initiation of the sensitive drug. Diagnostic delay in coinfections can lead to increased morbidity and mortality.
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Complicated clinical course of zoonotic tuberculosis due to Mycobacterium Caprae: A case report and literature review p. 466
Ata Yigit Çöllü, Nilay Uçarman, Gülsüm Iclal Bayhan
DOI:10.4103/ijmy.ijmy_148_22  
The incidence of human tuberculosis (TB) disease due to Mycobacterium caprae, an etiologic agent of zoonotic TB along with Mycobacterium bovis, is very low. There are no guidelines for human TB caused by M. caprae, and treatment protocols for infections caused by this microorganism are based on the recommendations for M. bovis infections. We report a 15-year-old girl diagnosed with cervical lymphadenitis due to M. caprae. She did not recover completely despite 6 months of anti-TB medication. Therefore, treatment was extended to 12 months. There is a lack of information about the treatment of human M. caprae infections. Further studies evaluating the treatment in detail are needed.
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Tuberculosis treatment-related lichenoid drug eruptions p. 469
Zeynep Yegin Katran, Ismet Bulut, Aylin Babalık
DOI:10.4103/ijmy.ijmy_151_22  
Tuberculosis is one of the leading causes of death from infectious diseases in adults worldwide. Drug hypersensitivity in tuberculosis is an important problem affecting the treatment process. Although treatment is started with isoniazid, rifampicin, ethambutol, and pyrazinamide in drug-sensitive tuberculosis patients, it may not always be continued in this way. When hypersensitivity develops under antituberculosis treatment, type 4 hypersensitivity is the most common, and maculopapular drug eruption develops as a subgroup. Lichenoid drug eruption is very rare. We present our case who was diagnosed with pulmonary tuberculosis, who developed lichenoid drug eruption while receiving treatment, and whose treatment was completed by giving the new regimen with successful desensitization.
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LETTER TO EDITOR Top

Large nonhealing cutaneous tubercular neck ulcer as a presenting feature of undiagnosed pulmonary tuberculosis: An atypical presentation p. 472
Preema Sinha, Parul Kamboj, Deepak Vashisht, Anamika Sinha, Saikat Bhattacharjee, Vineet Vij, Choudhary Sampoorna Raj
DOI:10.4103/ijmy.ijmy_180_22  
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