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   Table of Contents - Current issue
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January-March 2019
Volume 8 | Issue 1
Page Nos. 1-112

Online since Tuesday, March 12, 2019

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REVIEW ARTICLES  

The unexplained increase of nontuberculous mycobacteriosis Highly accessed article p. 1
Octavio Miguel Rivero-Lezcano, Carolina González-Cortés, Mehdi Mirsaeidi
DOI:10.4103/ijmy.ijmy_18_19  PMID:30860172
Epidemiological data show a worldwide increase in nontuberculous mycobacteriosis. Although it has been partially attributed to the improvement of microbiological methodologies that has allowed a better recovery and identification of nontuberculous mycobacteria (NTM), it is generally accepted that there is a genuine incidence augmentation. The reasons of the increase are likely multifactorial, depending on the nature of the pathogen, the host, and their interaction. Mycobacteria from the Mycobacterium tuberculosis complex has been regarded as pathogenic and NTM as opportunistic and nontransmissible. Nevertheless, few differences have been found in either their phenotypic or genotypic characteristics. The phenomenon of M. tuberculosis adaptation to the human host may be taking place again in NTM as a consequence of human environmental alterations that facilitate the interaction with the pathogen. The current worsening of the immunological status of increasing numbers of individuals, a result of factors such as malnutrition (obesity and diabetes), population aging or the widespread use of immunosuppressive medication, may be allowing the rapid evolution and person-to-person transmission of NTM. It is likely that mycobacteriosis incidence will keep escalating. New measures should be taken to deal with these diseases, including their reportability and the implementation of strain genotyping that would shed light on the NTM dissemination routes from the environment or human hosts.
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Antimycobacterial strategies to evade antimicrobial resistance in the nontuberculous mycobacteria Highly accessed article p. 7
Beverley Cherie Millar, John Edmund Moore
DOI:10.4103/ijmy.ijmy_153_18  PMID:30860173
The nontuberculous mycobacteria (NTM) have recently emerged as important bacterial pathogens of both animals and humans. Of particular, concern is the high level of antimicrobial resistance (AMR) displayed by these organisms, which complicates treatment and potential successful outcomes. This review, therefore, wishes to examine novel compounds and approaches to combatting AMR in the NTMs, specifically examining antimycobacterial (NTM) compounds from plants and venoms, as well as examining synergistic and combination effects with other antimicrobials. Novel and modified drugs including new inhaled drugs are examined, as well as the repurposing of existing drugs for antimycobacterial activity. Many of these novel interventions are at various stages of development, from initial concept through to licensed intervention. The challenge remains to translate these interventions from in vitro laboratory models to effective in vivo interactions. When these are realized, then we will have the opportunity of overcoming NTM AMR, to the benefit of medicine, society, and humanity.
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ORIGINAL ARTICLES Top

Drug resistance profile of Mycobacterium tuberculosis isolates from patients referred to tuberculosis reference laboratory in Kosovo p. 22
Rrezarta Bajrami, Gjyle Mulliqi, Arsim Kurti, Greta Lila, Lul Raka
DOI:10.4103/ijmy.ijmy_16_19  PMID:30860174
Background: Drug-resistant tuberculosis (TB) continues to threaten TB control and remains a major global public health concern. The poor patient adherence in TB treatment is the cornerstone of emerging multidrug-resistant TB (MDR-TB). The aim of this study was to evaluate the resistance of Mycobacterium tuberculosis to the first-line TB drugs among isolates from clinical specimens. Methods: A laboratory-based study was conducted in the Department of Microbiology, within the National Institute of Public Health of Kosovo, from January 2017 to September 2018. Sputum and other clinical specimens were obtained from patients with pulmonary and extrapulmonary TB. The specimens were stained with Ziehl–Neelsen, inoculated on Löwenstein–Jensen media for 6–8 weeks, and tested for sensitivity against the first-line TB drugs (isoniazid [INH], rifampicin [RIF], ethambutol [EMB], and streptomycin [SM]). Results: Of the 316 M. tuberculosis isolates collected, 31.6% showed resistance to first-line TB drugs. Among these resistant isolates, 31% showed resistance to at least one of the first-line TB drugs and 0.3% showed MDR. Resistance to EMB, INH, RIF, and SM was seen in 17%, 8%, 3%, and 72% of isolates, respectively. Polyresistance was seen in 3% of the isolates. Conclusion: Our study confirms that resistance to streptomycin was the most common phenomenon. The resistance pattern identified in this study could assist clinicians in providing appropriate treatment regimen to TB patients and improve their clinical outcome.
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Detection of multidrug resistant Mycobacterium tuberculosis in Tabuk, Saudi Arabia, using Genotype MTBDRplus p. 25
Eltayib Hassan Ahmed-Abakur, Tarig Mohammed Saad Alnour
DOI:10.4103/ijmy.ijmy_29_19  PMID:30860175
Background: The global increase in the rates of multidrug-resistant (MDR) tuberculosis (TB) has made the timely identification of resistant Mycobacterium tuberculosis complex strains an important emergence to achieve effective disease management and to prevent their spread in the community. The present study aimed to determine the MDR-TB in Tabuk province, north of the Kingdom of Saudi Arabia. Methods: The GenoType MTBDRplus assay was used to determine the mutations associated with isoniazid (INH) and rifampicin (RIF) resistances. A total number of 61 confirmed M. tuberculosis positive-sputum samples were scanned for the mutation in the rpoB, inhA, and katG genes. Results: The present study revealed that 67.2% of the samples were susceptible, 29.5% were monoresistant, and 3.3% were MDR. Conclusions: The monoresistant showed 26.2% for INH and 3.3% for RIF. The early detection of MDR could guide the starting of appropriate regimen of treatment.
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A retrospective study of the severe and uncommon variants of erythema nodosum leprosum at a tertiary health center in central India p. 29
Vaishali H Wankhade, Pritica Debnath, Rajesh Pratap Singh, Gitesh Sawatkar, Dharitri Mukund Bhat
DOI:10.4103/ijmy.ijmy_174_18  PMID:30860176
Background: Erythema nodosum leprosum (ENL) classically presents with tender, coppery, evanescent nodules along with constitutional features and visceral involvement. However, uncommon morphological variants of ENL-like erythema nodosum necroticans, erythema multiforme (EM)-like ENL, Sweet's syndrome (SS)-like ENL, Lucio phenomenon, and reactive perforating type of ENL have also been described in the literature. The primary objective of this study was to describe the clinical features of the severe and uncommon morphological variants of ENL. Methods: This was an observational case series with retrospective review of records of all ENL patients with ulceronecrotic lesions admitted in the Department of Dermato-venereo-leprology of a tertiary health center of central India over a period of 2 years. Results: Eighteen patients were included, all of whom had ulceronecrotic lesions. Four out of them had EM like ENL, two had SS-like presentation, and one of them had annular bullous lesions over old infiltrated plaques of leprosy. Conclusions: Uncommon variants of ENL can be very commonly misdiagnosed in patients, especially in those who have not been previously diagnosed with leprosy. Hence, a high index of suspicion is required in such cases to avoid delay in the diagnosis and resulting morbidity.
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Treatment outcomes and associated factors in tuberculosis patients at Jimma University Medical Center: A 5-year retrospective study p. 35
Gemeda Abebe, Zegeye Bonsa, Wakjira Kebede
DOI:10.4103/ijmy.ijmy_177_18  PMID:30860177
Background: Monitoring the outcome of tuberculosis (TB) treatment and investigating factors associated with unsuccessful outcome are essential, as unsuccessful treatment fuels resistance to antibiotics. This study aimed to investigate the treatment outcome and associated factors with an unsuccessful outcome at Jimma University Medical Center (JUMC), Southwest Ethiopia. Methods: A 5-year retrospective analytical study, including all types of TB cases who sought care at JUMC between September 1, 2012, and August 31, 2017, was conducted. Treatment outcomes and TB types were categorized according to the National TB Control guideline. Bivariate analysis was used to analyze the association between treatment outcome and potential variables. Results: Overall data from 1249 patients' records were included in the study. The proportion of male patients was higher (815, 65.3%) than that of females. The mean age (± standard deviation, range) of the cases was 26 (±11. 6, 1–71) years. Of the total, 292 (23.3%) were smear-positive pulmonary TB (PTB), 489 (39.2%) smear-negative PTB, and 468 (37.5%) extra-PTB (EPTB) cases. Available treatment outcomes indicate that 253 (20.2%) were cured, 850 (68.0%) completed therapy, 58 (4.8%) died, 83 (6.6%) defaulted, and 5 (0.4%) failed the therapy. About 76 (5.6%) cases were transferred out and 44 (3.2%) cases were lost to follow-up. In total, 146 (11.7%) patients had an unsuccessful outcome. Unsuccessful treatment outcome was associated with smear-negative PTB (odds ratio [OR] =2.0, 95% confidence intervals [CI] =1.1, 3.7), EPTB (OR = 2.1, 95% CI = 1.2, 3.4), and unknown human immunodeficiency virus (HIV) status (OR = 7.9, 95% CI = 2.5, 25.0). Conclusion: The treatment success rate of overall TB patients is lower than end TB Strategy target of ≥90% success rate. Smear-negative PTB, EPTB cases, and those with unknown HIV status tend to have unsuccessful outcome.
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Common alternative diagnoses among a pediatric hospital-based cohort evaluated for tuberculosis in Karachi, Pakistan: The need for facilitated referral in tuberculosis clinics p. 42
Sadia Shakoor, Fatima Mir, Rumina Hasan
DOI:10.4103/ijmy.ijmy_8_19  PMID:30860178
Background: Children evaluated for tuberculosis (TB) are often diagnosed with miscellaneous conditions that mimic TB. Knowledge of differentials informs policy on service provision through liaison with referral centers offering definitive diagnosis and treatment for common alternative disorders. Methods: We reviewed medical records of children who were offered diagnostic testing for TB (culture or Xpert MTB/RIF) at a tertiary care hospital in Karachi, Pakistan to identify common alternative diagnoses among children who are evaluated for TB. Results: From January 2014 to December 2015, of 126 culture or Xpert MTB/RIF negative children presenting with chronic symptoms, 31 were diagnosed and treated for TB based on clinical criteria (5 of 48 children with pulmonary and 26 of 78 with extrapulmonary presentations; 10.4% and 33.3%, respectively). Among remaining 95 patients, common alternative diagnoses to pulmonary TB (n = 43) were bacterial pneumonia or empyema (60.5%, n = 25) and underlying bronchiectasis (20.9%, n = 9). Among 52 extrapulmonary presentations, the most common alternative diagnoses were lymphoproliferative disorders (n = 11, 21.1%), bacterial infections (n = 11, 21.1%), and autoimmune disorders (n = 9, 17.3%). Of note, five children were diagnosed with underlying primary immunodeficiencies (9.6%). Children with alternative disorders were treated for TB in 25 of 95 cases (26.3%). Although 77.8% (n = 98) children were followed up at the facility, 15.9% (n = 20) were lost to follow-up. Conclusions: Pediatric TB mimics many disorders that primary level centers are not equipped to diagnose or manage, leading to suboptimal outcomes. Knowledge of common alternative diagnoses is essential to inform facilitated referral for common mimicking disorders in children.
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Survey of local fauna from endemic areas of Northern Queensland, Australia for the presence of Mycobacterium ulcerans p. 48
Avishek Singh, John Hannan William McBride, Brenda Govan, Mark Pearson
DOI:10.4103/ijmy.ijmy_168_18  PMID:30860179
Background: Buruli ulcer (BU), regionally known as the Daintree ulcer or Bairnsdale ulcer is caused by the environmental pathogen Mycobacterium ulcerans (MU). This disease is characterized by extensive and painless necrosis of skin and soft tissue with the formation of large ulcers and has been reported in >33 countries worldwide. This organism is geographically restricted and in Australia, the disease has been reported primarily in coastal Victoria and the Mossman–Daintree areas of northern Queensland. Australia is the only country where nonhuman cases of BU have been confirmed. The common ringtail possums and mountain brushtail possums have been suggested as potential animal reservoirs of MU in coastal Victoria, Australia. The exact mode of transmission of this disease remains unknown. Methods: In this study, we surveyed local fauna from endemic areas of northern Queensland, Australia, for the presence of MU in scat samples. We collected 140 bandicoot, four white-tailed rats, and two possum scat samples from 56 overnight trapping sessions. Samples were examined for the presence of MU DNA by the polymerase chain reaction. Results: Two out of five samples did not contain a sufficient amount of DNA to detect IS2606 and the ketoreductase B (KR) domain of the mycolactone polyketide synthase gene, which is represented by higher cycle threshold (Ct) values for IS2404 shown in table below. Despite of having desired Ct values for IS2404, one IS2404 positive sample possibly contained DNA of closely related M. ulcerans subspecies with lower copy number of IS2606 that do not commonly cause disease in human. All three targets: IS2404, IS2606 and KR were detected from the remaining two scat samples. Conclusion: We confirm the presence of M. ulcerans DNA in the scat samples collected from a Buruli ulcer endemic region of Northern Queensland, Australia.
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Blood cytokine responses to early secreted protein antigen-6/culture filtrate protein-10 tuberculosis antigens 2 months after antituberculosis treatment among patients with drug-susceptible pulmonary tuberculosis p. 53
Happiness Cornel Mvungi, Peter Masunga Mbelele, Joram Josephat Buza, Stellah George Mpagama, Elingarami Sauli
DOI:10.4103/ijmy.ijmy_30_19  PMID:30860180
Background: Human tuberculosis is a chronic inflammatory disease caused by mycobacterium tuberculosis. Pulmonary tuberculosis is the result of the failure of host immune system to control mycobacterium tuberculosis. The aim of the study was to asses the changes of the cytokines in active pulmonary tuberculosis patients before and after the use of anti-TB therapy. Methods: Multiple cytokine responses in active tuberculosis (TB) patients were investigated in this study following anti-TB drug therapy after 2 months. Ninety-six participants with pulmonary TB were engaged in the study between May 2018 and October 2018. Samples of blood were taken early before treatment at 0 and 2 months after using anti-TB therapy. The levels of interferon-gamma (IFN)-γ, interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor (TNF)-α in whole blood plasma collected from the QuantiFERON-TB Gold Plus were measured. Results: Compared with baseline levels, TNF-α, IL6 and IL10 were significantly lower following treatment whereas the IFN-γ and IL-4 increased significantly after treatment. The responses of five cytokines varied significantly after treatment (P < 0.0001) where IFN-γ was highest compared to other cytokines with 123.6%, AUC=0.757 and P < 0001, TNF-α AUC: 0.529 and P = 0.743, IL-4 AUC:0.557 and P = 0.514, IL-6 AUC:0.629 and P = 0.047, IL-10 AUC:0.549 and P = 0.581. Conclusion: It is concluded that changes of cytokines that observed during the treatment of TB patients play a very important role in monitoring pulmonary TB and can be suitable biomarkers to assess the effectiveness of anti-TB therapy in patients with TB.
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Tuberculosis transmission in the population of patients from the Krakow Region (Poland) based on the epidemiological and molecular methods p. 60
Katarzyna Kruczak, Ewa Augustynowicz-Kopeć, Monika Kozińska, Grażyna Passak-Stańda, Ewa Niżankowska-Mogilnicka, Krzysztof Sładek
DOI:10.4103/ijmy.ijmy_11_19  PMID:30860181
Background: The transmission of tuberculosis may affect the incidence rate of the disease in Poland. Genetic methods are of assistance in tracing the infection transmission, identifying its sources, determining the risk groups, and focusing on the preventive actions. Objectives: The objectives of this study lie in an assessment of tuberculosis transmission by genetic methods with the assistance of the standard epidemiologic interview. Methods: The genome DNA of 275 Mycobacterium tuberculosis (Mtb) strains from tuberculosis patients, inhabitants of the city of Krakow, was subjected to a genetic analysis via the spoligotyping method and the IS6110-Mtb1–Mtb2 polymerase chain reaction (PCR) method. If the DNA profiles were identical in both of the PCRs, they were considered identical and classified within one molecular family. Results: Among 275 strains, 104 genetic patterns (spoligotypes) were identified. Two hundred and three strains were divided into 66 molecular families (clusters) and analyzed with the IS6110- Mtb1–Mtb2 PCR method. Eighteen clusters were separated. In the Mtb1–Mtb2 clusters, 21 patients were in the risk groups (the homeless, prisoners, and nursing home residents). We did not confirm any direct or temporary contacts between the patients constituting the Mtb1–Mtb2 clusters (apart from the risk groups). However, the patients in these clusters often lived in the same parts of Krakow. Conclusions: The standard epidemiologic interview in tuberculosis patients should be combined with genetic methods. Active transmission of tuberculosis occurs largely among the individuals maintaining probably periodic contacts. The patients who are in the risk groups may play an important role in the transmission of tuberculosis.
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Upregulated bovine tuberculosis microRNAs Trigger oncogenic pathways: An In silico perception p. 70
Elvis Ndukong Ndzi, Ambily Nath Indu Viswanath, Nsadzetsen Gilbert Adzemye, Ousman Tamgue, Munji Victorine Nsongka, Achuthsankar S Nair, Céline Nguefeu Nkenfou
DOI:10.4103/ijmy.ijmy_9_19  PMID:30860182
Background/Objective: Although microRNA (miRNA)-directed regulation of bovine tuberculosis (bTB) has already been reported, very little is known about the incited pathways and genes. We profiled bTB-upregulated miRNAs through an in silico methodology. Methods: The data of upregulated miRNAs in bTB versus healthy controls were collected and clustered into three groups by their tissue specificity as follows: G1 (mammary gland-specific): bta-miR-146a; G2 (peripheral blood mononuclear cell-specific): bta-miR-155; and G3 (alveolar macrophage-specific): bta-miR-146a, bta-miR-155, bta-miR-142-5p, bta-miR-423-3p, bta-miR-21-5p, bta-miR-27a-3p, bta-miR-99b, bta-miR-147, bta-miR-223, and bta-let-7i. The miRNA–mRNA interaction network was defined by TargetScan. The gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of these transcripts were examined. Results: The results illustrate the induction of pathways in cancer, highly enriched, and unanimous to all three gene sets (G1, G2, and G3). Mitogen-activated protein kinase and PI3K-Akt signaling were specific to G2 and G3 with fibroblast growth factors formed the key factors. Conclusion: The inferred cancer cascades denote a probable modulation of innate immune response in an infectious state. These baseline pictures could lay the ground for further substantive studies.
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Evaluation of microbiological variants of sputum processing and concentration of mycobacteria to optimize the microscopic and imaging diagnosis of tuberculosis p. 75
Jorge E Coronel, Christian C Del Carpio, Erwin J Dianderas, Edgar A Florentini, Guillermo L Kemper, Patricia Sheen, Mirko J Zimic
DOI:10.4103/ijmy.ijmy_172_18  PMID:30860183
Background: Direct sputum smear is still the first-choice tool for screening of tuberculosis worldwide. Variants of this technique, to improve the sensitivity are desired. Methods: Two microbiological variants of the standard sputum smear (”pellet” and “diluted-pellet”) for both Ziehl-Neelsen (ZN) and auramine fluorescence (AF) staining were evaluated. In addition, two methods for concentration of mycobacteria in sputum, using positive and negative pressure filtration, were tested and compared. The evaluation of the microbiological variants was performed on 98 culture positive sputum samples from different TB patients. The diagnostics sensitivity and the level of detritus in the processed sputum were determined. Bacilli load in the smear variants was determined by microscopic observation and by manual inspection of microscopic digital images. The comparison of the mycobacteria filtration methods was performed on 76 smear positive sputum samples. Filters retaining the concentrated mycobacteria were stained with AF and compared with the direct smear. Bacilli load, detritus level, filtered volume, filtration time and background noise level, were determined. Results: The sensitivity of microscopy with the microbiological variants was 7.1% and 2% higher in ZN and AF respectively, compared to direct smear. The sensitivity of AF in diluted pellet was significantly higher than all ZN variants (P < 0.05). Detritus level observed in slides was significantly lower in the diluted pellet than the pellet and direct smear in ZN and AF (P < 0.001). A significant increase in the bacilli load in microscopic observation and digital images analysis was observed in pellet and diluted pellet than the direct method (P <0.0001). The concentration of mycobacteria using positive-pressure filtration showed a trend to produce a higher bacilli load compared to the negative-pressure filtration and direct smear, although it was not significant. Detritus levels were significantly higher in both variants of filtration (P < 0.0001). Filtered volumes were higher in positive-pressure compared to negative-pressure filtration. Filtration times were significantly higher in negative-pressure compared to positive-pressure filtration (P < 0.0001). Conclusion: The proposed variants improved the performance of the standard sputum smear, making it an important test for settings with high rates of smear-negative TB cases.
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Validation of the GenoType® MTBDRplus Ver 2.0 assay for detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis complex isolates at UZCHS-CTRC TB research laboratory p. 83
Stephen Stephen, Donhodzo Muzhizhizhi, Nicholas Dhibi, Tinashe Chidemo, Wadzanai Samaneka, Taguma Allen Matubu, James Gita Hakim, Zvavahera Mike Chirenje
DOI:10.4103/ijmy.ijmy_170_18  PMID:30860184
Background: Multidrug-resistant tuberculosis (MDR-TB) is a public health concern globally. MDR-TB is defined as resistance to rifampicin (RIF) and isoniazid (INH), the two-major anti-TB first-line TB treatment drugs. Rapid identification of MDR-TB can contribute significantly to the control of TB. The GenoType® MTBDRplus Ver 2.0 assay is a molecular assay used to detect genetic mutations that result in RIF and INH resistance. The aim of this study was to validate the performance of the GenoType® MTBDRplus Ver 2.0 assay for the detection of INH and RIF resistance. Methods: Fifty-five stored Mycobacterium tuberculosis isolates were tested using both the mycobacterial growth indicator tube (MGIT), antimicrobial susceptibility testing (AST), and the GenoType® MTBDRplus Ver 2.0 assay. The MGIT AST was done according to the BBL MGIT AST SIRE system with RIF and INH final critical concentrations of 1.0 μg/ml and 0.1 μg/ml, respectively. The GenoType® MTBDRplus assay (Hain Lifescience, Germany) was performed following the manufacturer's instructions. Results: The GenoType® MTBDRplus Ver 2.0 assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 100% for INH and RIF resistance. The intra-assay precision for the assay was 100%. Conclusion: The GenoType® MTBDRplus Ver 2.0 assay's sensitivity and specificity show that the assay is highly accurate for the detection of RIF and INH resistance and thus can be used as an alternate platform due to its shorter results turnaround time.
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Ursodeoxycholic acid attenuates hepatotoxicity of multidrug treatment of mycobacterial infections: A prospective pilot study p. 89
Susanne M Lang, Johannes Ortmann, Sven Rostig, Helmut Schiffl
DOI:10.4103/ijmy.ijmy_159_18  PMID:30860185
Background: Tuberculosis (TB) remains a global health problem. The application of rifampicin-based regimens for antimycobacterial therapy is hampered by its marked hepatotoxicity which results in poor adherence and may contribute to prolonged therapy or treatment failure. The purpose of this prospective investigation was to evaluate the hepatoprotective effectiveness of oral ursodeoxycholic acid (UDCA) (250–500 mg TID) administered to TB- or non-TB mycobacterial (NTM)-infected patients with drug-induced hepatotoxicity and ongoing therapy. Methods: Study population: During 2009–2017, 27 patients (11 women, 16 men, aged 19–90 years; median age 44 years, 16 Caucasians, 10 Africans, 1 Asian) out of 285 patients with active TB (24/261) or NTM infections (3/24) treated at our TB Center developed clinically relevant hepatotoxicity. Oral UDCA was administered to treat hepatotoxicity. Results: Twenty-one out of 27 patients (77.8%) showed normalization of elevated enzymes (alanine transferase and aspartate aminotransferase), alkaline phosphatase, and bilirubin while continuing TB treatment and 5 patients demonstrated a significant reduction of liver enzymes (18.5%). No change was observed in 1 patient (3.7%). Drug dose was not reduced in all patients; they all showed radiological and clinical improvement. There were no significant side effects. Conclusion: Oral administration of UDCA to TB patients developing anti-TB drug-induced liver injury may reverse hepatotoxicity in adults.
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Antimicrobial properties of basidiomycota macrofungi to Mycobacterium abscessus isolated from patients with cystic fibrosis p. 93
Beverley Cherie Millar, David Nelson, Rachel E Moore, Juluri R Rao, John E Moore
DOI:10.4103/ijmy.ijmy_167_18  PMID:30860186
Background: Antimicrobial resistance (AMR) has now emerged as a global public health crisis. Of particular concern is AMR associated with the genus Mycobacterium, including Mycobacterium tuberculosis and the nontuberculous mycobacteria (NTM). Emergence of the NTM, in particular Mycobacterium abscessus, in patients with cystic fibrosis (CF) represents both a diagnostic and a treatment dilemma. Such resistance drives the need to investigate novel sources of antimicrobials. Medicinal fungi have a well-documented history of use in traditional oriental therapies. Not only is this an ancient practice, but also still today, medical practice in Japan, China, Korea, and other Asian countries continue to rely on fungal-derived antibiotics. A study was, therefore, undertaken to examine the antimicrobial activity of 23 native macrofungal (mushrooms/toadstools) taxa, collected from woodlands in Northern Ireland against six clinical (CF) isolates of M. abscessus, as well as M. abscessus National Collection of Type Cultures (NCTC) Reference strain (NCTC 13031). Methods: Free-growing saprophytic and mycorrhizal macrofungi (n = 23) belonging to the phylum Basidiomycota were collected and were definitively identified employing Polymerase Chain reaction/ITS DNA sequencing. Macrofungal tissues were freeze-dried and reconstituted before employment in antibiotic susceptibility studies. Results: All macrofungi examined showed varying inhibition of the M. abscessus isolates examined with the exception Russula nigricans. The macrofungi displaying maximum antimycobacterial activity against the clinical isolates were (in descending order) M. giganteus (33.6 mg/ml), Hygrocybe nigrescens (38.5 mg/ml) and Hypholoma fasciculare (25.3 mg/ml). Conclusion: Macrofungi may represent a source of novel antimicrobials against M. abscessus, which have not yet been fully explored nor exploited clinically. This is the first report describing the antimycobacterial properties of extracts of M. giganteus against M. abscessus. Further work is now required to identify the constituents and mode of the inhibitory action of these macrofungi against the M. abscessus. Given the gravity of AMR in the NTMs, particularly M. abscessus and the clinical treatment dilemmas that such AMR present, antibiotic drug discovery efforts should now focus on investigating and developing antibacterial compounds from macrofungi, particularly M. giganteus, where there are no or limited current treatment options.
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CASE REPORTS Top

Disseminated Mycobacterium intracellulare from a Deep Cutaneous Infection p. 98
Adam Stewart
DOI:10.4103/ijmy.ijmy_17_19  PMID:30860187
Primary cutaneous Mycobacterium avium complex (MAC) infection is a rare diagnosis in both immunocompetent and immunocompromised hosts. Disseminated MAC almost always occurs in the setting of advanced HIV infection and typically results from initial pulmonary or gastrointestinal disease. We describe a case of a 70-year-old female with systemic sclerosis and severe tumoral calcinosis that developed disseminated MAC infection secondary to deep cutaneous disease. Treatment was complicated by multiple significant drug interactions, patient comorbidities, as well as an inability to safely and completely surgically resect her infected soft tissue for source control.
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Tuberculosis of pancreas, the first case reported from Qatar p. 101
Maisa Ali, Adila Shaukat, Zubaida Al-Suwaidi, Muna Al-Maslamani
DOI:10.4103/ijmy.ijmy_147_18  PMID:30860188
Despite the high prevalence of tuberculosis (TB) in developing countries, primary pancreatic TB is a rare entity. We present a case of pancreatic TB in an immunocompetent patient who was found to have pancreatic mass resembling malignancy. A 40-year-old Indian male presented to the medical emergency room with complaints of abdominal pain and fever for 2 weeks' duration. He had a history of unintentional weight loss of about 20 pounds in the past 2 months. There was no significant history of exposure to TB patient. Family history was unremarkable for any malignancy. On examination, the significant finding was epigastric tenderness. He was thoroughly investigated, his purified protein derivative and QuantiFERON were negative. Chest X-ray was unremarkable. Computed tomography scan abdomen was performed that revealed large heterogenous necrotic mass in the lesser sac likely arising from pancreatic body with possible infiltration of the stomach, left lobe of the liver and encasing celiac vessels and portal vein with multiple peripancreatic and retroperitoneal necrotic lymph nodes. Endoscopic ultrasound with fine-needle aspiration of pancreatic mass was done, biopsy specimen revealed the presence of inflammation with no evidence of malignancy. TB polymerase chain reaction and culture came positive for Mycobacterium tuberculosis. He was started on antituberculosis treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol with a plan to continue for total 6 months. However, follow-up of the patient could not be done as he traveled back to his home country.
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Central nervous system tuberculosis reactivation following intravenous iron supplementation p. 104
Stamatis Karakonstantis, Evgenia Emmanouilidou, Kiriaki Petraki, Charalampos Lydakis
DOI:10.4103/ijmy.ijmy_10_19  PMID:30860189
Patients with inflammatory bowel disease (IBD) are often treated with tumor necrosis factor (TNF)-alpha inhibitors and are therefore at higher risk for tuberculosis (TB) reactivation. IBD patients also frequently have iron deficiency which is often treated with intravenous iron supplementation. Iron plays an important role in mycobacterial infections, and reactivation of TB has been rarely reported after iron repletion. We present a case of a 63-year-old male with a history of Crohn's disease, on treatment with adalimumab for 2 years. The patient presented with malaise, mild lethargy, low-grade fever, and hyponatremia within a week after the first dose of intravenous iron. He was diagnosed with central nervous system TB (positive cerebrospinal fluid polymerase chain reaction and culture) and responded to treatment with a four-drug regimen. The timing of TB reactivation (within a week after intravenous iron administration) suggests that iron repletion contributed to the clinical reactivation of TB. Biological plausibility and prior similar clinical observations further support the causality of this association. Considering the frequency of iron deficiency in IBD, we believe that it is worthy to further explore the potential association between intravenous iron administration and the timing of TB reactivation in patients being treated with TNF-alpha inhibitors.
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Immune thrombocytopenic purpura in a patient with disseminated tuberculosis: An unusual presentation p. 107
Prashant Nasa, Deven Juneja, Sudhish Sehra, HK Singh, Deen Bandhu Prasad
DOI:10.4103/ijmy.ijmy_169_18  PMID:30860190
Pulmonary tuberculosis can have a wide variety of presentations including hematological manifestations. We report a case of a young male patient who presented with complaints of generalized petechiae, gum bleeding, systemic lymphadenopathy, and severe thrombocytopenia. His bone marrow revealed normal megakaryocytes, and in the absence of hepatosplenomegaly, a diagnosis of immune thrombocytopenic purpura (ITP) was made. The thrombocytopenia responded to course of intravenous immune globulin. The smear made from fine-needle aspiration of cervical lymph nodes showed acid-fast bacilli. This case highlights the rare association of extrapulmonary tuberculosis with ITP.
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Tubercular aortitis presenting as primary aortoenteric fistula: Report of an uncommon case p. 110
Ajay Savlania, Vibhav Sharma, Pulkit Rastogi, Harjeet Singh, Vishal Sharma, Harshal S Mandavdhare
DOI:10.4103/ijmy.ijmy_32_19  PMID:30860191
Tubercular aortitis presenting as primary aortoenteric fistula (AEF) is a rare entity. We present a 78-year-old male who presented with upper gastrointestinal bleed and also had abdominal pain and pulsating abdominal mass and on evaluation was found to have tubercular AEF which was successfully repaired with surgery and the patient recovered with antitubercular therapy along with the surgery. This case highlights the importance of high index of suspicion with early institution of surgical repair along with antitubercular therapy for tubercular AEF with good results.
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