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   Table of Contents - Current issue
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April-June 2020
Volume 9 | Issue 2
Page Nos. 107-230

Online since Friday, May 29, 2020

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REVIEW ARTICLE  

An evidence-based clinical pathway for the diagnosis of tuberculous lymphadenitis: A systematic review Highly accessed article p. 107
Lavanyah Sivaratnam, Azmawati Mohammed Nawi, Mohd Rizal Abdul Manaf
DOI:10.4103/ijmy.ijmy_207_19  PMID:32474531
To achieve the World Health Organization end TB Strategy, early detection, and prompt treatment of not only pulmonary but also extrapulmonary tuberculosis (EPTB) should be achieved. The most common EPTB is tuberculous lymphadenitis, and the diagnosis is typically time-consuming. This review aimed to identify the best diagnostic pathway for preventing treatment delay and thus further complications. A systematic keyword search was done using four databases and other relevant publications and using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart to search for relevant articles that met the inclusion criteria. The quality of the articles was assessed using Newcastle–Ottawa Scale, and the articles were summarized based on the test for diagnosing tuberculous lymphadenitis. A total of ten articles were included for the synthesis of results, which compared the sensitivity and specificity of each diagnostic test for tuberculous lymphadenitis. The most promising test is the Xpert Mycobacterium tuberculosis/RIF, which has high sensitivity and specificity, but costs much more in comparison to the other tests. An ideal diagnostic method should include the combination of relevant patient history, clinical examination, and laboratory and radiological testing to avoid delays in treatment, misdiagnosis, and further complications.
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ORIGINAL ARTICLES Top

Co-infection by dimorphic fungi in tuberculosis patients in Kenya p. 116
Joseph K Ngei. Kuria, Donald Mogoi, Samuel Guchu Gachuhi
DOI:10.4103/ijmy.ijmy_44_20  PMID:32474532
Background: Dimorphic fungi may cause infections and symptoms similar to tuberculosis (TB), in humans and animals. Such infections, individually or concurrently with TB, have been identified in cattle in Kenya, raising the possibility of infections in other animals, including humans. The study aimed to identify and quantify dimorphic fungi co-infection in persons with TB. Methods: Smear-positive sputum samples, 400, were obtained from TB clinics between October 2016 and November 2017. The samples were examined microscopically for yeast fungi, cultured for isolation of yeast, conversion to molds, and conversion from molds to yeasts. The isolates were characterized morphologically. Results: Blastopores, with morphological characteristics of Paracoccidiodes and Blastomyces, were observed in 37 smears of the sputum samples. Similar yeast cells were observed in smears of the sputum cultures. The yeast cultures were converted to molds on incubation at room temperature and back to yeasts on incubation at 37°C. Conclusion: Dimorphic fungi, morphologically identified as Paracoccidiodes and Blastomyces, concomitantly infect a proportion of TB patients in the study area. It is recommended that routine diagnosis for TB should consider infection or co-infection by dimorphic fungi for institution of appropriate treatment.
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Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru Highly accessed article p. 121
Ana Paula Vargas, Angela A Rios, Louis Grandjean, Daniela E Kirwan, Robert H Gilman, Patricia Sheen, Mirko J Zimic
DOI:10.4103/ijmy.ijmy_27_20  PMID:32474533
Background: Rifampicin (RIF) resistance in Mycobacterium tuberculosis is frequently caused by mutations in the rpoB gene. These mutations are associated with a fitness cost, which can be overcome by compensatory mutations in other genes, among which rpoC may be the most important. We analyzed 469 Peruvian M. tuberculosis clinical isolates to identify compensatory mutations in rpoC/rpoA associated with RIF resistance. Methods: The M. tuberculosis isolates were collected and tested for RIF susceptibility and spoligotyping. Samples were sequenced and aligned to the reference genome to identify mutations. By analyzing the sequences and the metadata, we identified a list of rpoC mutations exclusively associated with RIF resistance and mutations in rpoB. We then evaluated the distribution of these mutations along the protein sequence and tridimensional structure. Results: One hundred and twenty-five strains were RIF susceptible and 346 were resistant. We identified 35 potential new compensatory mutations, some of which were distributed on the interface surface between rpoB and rpoC, arising in clusters and suggesting the presence of hotspots for compensatory mutations. Conclusion: This study identifies 35 putative novel compensatory mutations in the β' subunit of M. tuberculosis RNApol. Six of these (S428T, L507V, A734V, I997V, and V1252LM) are considered most likely to have a compensatory role, as they fall in the interaction zone of the two subunits and the mutation did not lead to any change in the protein's physical–chemical properties.
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Mycolicibacterium smegmatis possesses operational agmatinase but contains no detectable polyamines p. 138
Mikhail Zamakhaev, Ivan Tsyganov, Larisa Nesterova, Anna Akhova, Artem Grigorov, Julia Bespyatykh, Tatyana Azhikina, Alexander Tkachenko, Mikhail Shumkov
DOI:10.4103/ijmy.ijmy_48_20  PMID:32474534
Background: Polyamines are widespread intracellular molecules able to influence antibiotic susceptibility, but almost nothing is known on their occurrence and physiological role in mycobacteria. Methods: here, we analyzed transcriptomic, proteomic and biochemical data and obtained the first evidence for the post-transcriptional expression of some genes attributed to polyamine metabolism and polyamine transport in Mycolicibacterium smegmatis (basionym Mycobacterium smegmatis). Results: in our experiments, exponentially growing cells demonstrated transcription of 21 polyamine-associated genes and possessed 7 enzymes of polyamine metabolism and 2 polyamine transport proteins. Conclusion: Mycolicibacterium smegmatis putrescine synthesizing enzyme agmatinase SpeB was originally shown to catalyze agmatine conversion to putrescine in vitro. Nevertheless, we have not found any polyamines in mycobacterial cells.
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Spectrum of pulmonary fungal pathogens, associated risk factors, and anti-fungal susceptibility pattern among persons with presumptive tuberculosis at Gombe, Nigeria p. 144
Fatima Muhammad Sani, Auwalu Uba, Fatima Tahir, Idris Nasir Abdullahi, Hafeez Adeinsayo Adekola, Jelili Mustapha, Justin Nwofe, Yahaya Usman, Isah Muhammad Daneji
DOI:10.4103/ijmy.ijmy_46_20  PMID:32474535
Background: Pulmonary mycosis (PM) poses a great diagnostic challenge due to the lack of pathognomonic and radiological features, especially in the absence of mycology laboratory tests. This study was aimed to isolate, phenotypically identify, determine the prevalence of pulmonary fungal pathogens and antifungal susceptibility pattern of isolates of presumptive tuberculosis (PTB) patients attending Federal Teaching Hospital (FTH) Gombe, Nigeria. Methods: After ethical approval, three consecutive early morning sputa were collected from 216 participants with presumptive of PTB attending FTH Gombe, between May 2, 2017 and May 30, 2018. Samples were processed using standard mycological staining, microscopy, sugar biochemistry, and antifungal susceptibility test protocols. Sociodemographic variables and risk factors of pulmonary fungal infection were assessed through structured questionnaires. Pulmonary fungal infection was defined by the positive culture in at least two sputa. PTB was defined by Genexpert® nested polymerase chain reaction. Results: Of the 216 participants, 19.9% had PTB and 73.6% had pulmonary fungal pathogens. Among the isolated pulmonary fungal pathogens, Aspergillus fumigatus made the highest occurrence, while 6.5% had PTB-fungal co-infection. No significant association existed between the prevalence of PM with age and sex of participants (P < 0.05). Cigarette smoking (adjusted odds ratio [aOR] = 15.9 [95% confidence interval (CI): 0.9–268.8]), prolong antibiotic use (aOR = 77.9 [95% CI: 4.7–1283]) and possession of domestic pet (aOR = 77.9 [95% CI: 4.7–1283]) were significant risk factors of PM (P < 0.05). Penicillium citrinum, Mucor spp. and Aspergillus flavus are more susceptible to voriconazole, and Candida albicans was found to be more susceptible to Nystatin. Of the 159 fungal isolates, 92.5% were resistant to fluconazole. Conclusion: Findings from this study revealed high level pulmonary fungal pathogens, especially among PTB patients. A majority of fungal isolates were resistant to fluconazole. It's recommended that persons should do away with or minimize risk factors for pulmonary fungal pathogens identified in this study.
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Antimycobacterial screening of selected medicinal plants against Mycobacterium tuberculosis H37Rv using agar dilution method and the microplate resazurin assay p. 150
Khushboo Dhirajlal Jethva, Dhara Rajendrakumar Bhatt, Maitreyi N Zaveri
DOI:10.4103/ijmy.ijmy_60_20  PMID:32474536
Background: Tuberculosis (TB), has been serious disease to the global human population causing millions of deaths worldwide. The recent increase in the number of multi-drug resistant clinical isolates of Mycobacterium tuberculosis has created an urgent need for the discovery and development of new anti-TB drugs. Medicinal plants have had a great influence on the daily lives of people living in developing countries, particularly in India. Medicinal plants were selected, and they were evaluated for its anti-TB activity against the pathogenic strain of M. tuberculosis H37Rv. Methods: Eleven medicinal plants were selected on the basis of its literature survey, and three different extracts were prepared. Antimycobacterial activities were screened using two in vitro assays, namely agar dilution assay and microplate resazurin assay against M. tuberculosis H37Rv at different concentrations of prepared extracts. We analyzed minimal inhibition concentrations and percentage of inhibition of the used strain of Mycobacteria. Isoniazid was used as a standard anti-TB drug. Results: The results of this study showed that aqueous extracts four selected medicinal plants Ocimum sanctum, Adhatoda vasica, Leptadenia reticulata, and Cocculus hirsutus having minimum inhibitory concentration at 500 μg/ml, 500 μg/ml, 250 μg/ml, and 250 μg/ml, respectively, and O. sanctum (60.24%), A. vasica (62.89%), L. reticulata (74.26%), and C. hirsutus (81.67%) showed significant anti-TB activity against M. tuberculosis. Conclusion: This study helps society to found new anti-TB agents having better anti-TB activity with lesser or no side effects.
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VapBC and MazEF toxin/antitoxin systems in the regulation of biofilm formation and antibiotic tolerance in nontuberculous mycobacteria p. 156
Daria V Eroshenko, Tatyana V Polyudova, Anna A Pyankova
DOI:10.4103/ijmy.ijmy_61_20  PMID:32474537
Background: Mycobacterium smegmatis and other nontuberculous mycobacteria (NTM) are widely distributed in the environment, but a significant increase of NTM infections has taken place in the last few decades. The objective of this study was to determine the role of toxin–antitoxin (TA) vapBC and mazEF systems that act as effectors of persistence in the stress response of NTM. Methods: The growth ability and the biofilm formation of NTM were evaluated by conventional methods. Bacterial cell viability was determined using MTT staining, agar plating, or the method of limiting dilutions. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of antibiotics were estimated using broth and agar dilution methods. Results: Despite a comparable growth dynamics and biofilm formation on solid/liquid interface with the wild type, a M. smegmatis vapBC, mazEF, and vapBC × mazEF deletion mutant produced more abundant pellicle and were more susceptible to heat shock. Significant differences were also found in the resistance wild type of NTM to isoniazid and ciprofloxacin reflected by higher MBC/MIC ratios. The proposed method of cultivation of agar blocks without visible growth after MIC determination into a liquid medium allows us to detect transition of all wild type of NTM strains to a dormant state in the presence of subMICs of isoniazid and ciprofloxacin while all deletion mutants failed to form dormant cells. Conclusion: Our data suggest that both vapBC and mazEF TA systems putatively involved in the heat and antibiotic stress response of NTM via their key role in transition to the dormant state.
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Hospitalizations for tuberculous peritonitis in the United States: Results from the national inpatient sample database from 2002 to 2014 p. 167
Eric Martin Sieloff, Adam Timothy Ladzinski, Neiberg de Alcantara Lima, Duncan Vos, Harry Boamah, Thomas Andrew Melgar
DOI:10.4103/ijmy.ijmy_68_20  PMID:32474538
Background: Tuberculosis (TB) is an uncommon disease in the Western hemisphere that can present with peritoneal involvement, as tuberculous peritonitis(TBP) causing abdominal pain and fever. The healthcare and economic burden of TBP in the United States remains unknown. Methods: The National Inpatient Sample database was utilized to investigate TBP hospitalizations from 2002 to 2014. Economic expenditures, patient and hospital demographics, and associations of certain comorbidities with TBP were analyzed. Results: A total of 5878 hospitalizations for TBP occurred over the 12-year duration, with $420 million in-hospital charges. The median patient age was 45 years (interquartile range: 31.1–61.7), with the majority being Hispanic (27.15%). Hospitalizations occurred primarily in the Western (31.3%) and Southern (31.7%) United States. Patient comorbidities and the respective odds ratio associated with TBP included HIV (33.56), continuous peritoneal dialysis (10.49), malnutrition (7.38), liver cirrhosis (6.87), and liver cirrhosis sequelae (6.91). Nearly 6.37% of TBP hospitalizations also had active pulmonary TB. Conclusion: Although TBP is uncommon in the United States, it should be considered in patients presenting with abdominal pain and fever and a history of HIV, continuous peritoneal dialysis, malnutrition, liver cirrhosis, or liver cirrhosis sequelae.
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Susceptibility of the Mycobacterium abscessus complex to drying: Implications for nebulizer hygiene in patients with cystic fibrosis p. 173
John Edmund Moore, Beverley Cherie Millar
DOI:10.4103/ijmy.ijmy_62_20  PMID:32474539
Background: Nebulizer hygiene and care is important in cystic fibrosis (CF) to minimize device contamination from bacteria, including nontuberculous mycobacteria (NTMs). Most nebulizer manufacturers recommend nebulizer drying, however there is little evidence to understand how nebulizer drying affects NTM survival. Methods: Mycobacterium abscessus subsp. massiliense (n = 2), M. abscessus subsp. bolletii (n = 2), and M. abscessus subsp. abscessus (n = 2) were evaluated for their ability to survive simulated drying conditions associated with routine nebulizer care. Bacterial inocula (circa. 107 colony-forming units) were added to plastic and allowed to dry to completeness for 24 h, employing passive and active drying. Results: NTM isolates of all subspecies could be recovered from all passive and active drying experiments, both in diluent and in sterile sputum, following drying (24 h). There was no combination of drying or physiology that supported NTM cell death, and there was no difference in observed survival with the three species of M. abscessus examined. Conclusion: This study indicates that drying, either passively or actively, for 24 h at room temperature, is unable to eradicate all M. abscessus organisms from dry plastic surfaces, even in the presence of residual sputum contamination. Whilst drying may be advantageous for nebulizer performance, it should not be regarded as an absolute control for the elimination of NTM organisms. With nebulizer hygiene, NTM organisms would be able to survive on a nebulizer following drying for 24 h, which has not undergone any formal disinfection protocol. Therefore, for NTM eradication from washed nebulizers, CF patients should therefore seek an effective alternative control to drying for NTM eradication, i.e., heat disinfection in baby bottle disinfectors. CF patients and health-care professionals should not rely solely on nebulizer drying to achieve NTM eradication.
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Analysis of Mycobacterium tuberculosis Uptake by Alveolar Macrophages after Ex vivo Expansion Indicates Processing Host Cells with Pathogen Actually from Lung Tissue of Patients with Pulmonary Tuberculosis p. 176
Elena Ufimtseva, Natalya Eremeeva, Sergey Bayborodin, Tatiana Umpeleva, Diana Vakhrusheva, Sergey Skornyakov
DOI:10.4103/ijmy.ijmy_39_20  PMID:32474540
Background: Previously, the ex vivo cultures of alveolar macrophages were developed from the surgical samples of the lungs in patients with pulmonary tuberculosis (TB) to establish the unique features of Mycobacterium tuberculosis (Mtb) lifestyle in host cells, but the question has remained whether Mtb-infected cells are isolated from the human lungs or they may be the result of Mtb phagocytosis in ex vivo culture. The study was aimed to investigate Mtb uptake by TB patients' cells after ex vivo expansion. Methods: Alveolar macrophages were infected with the Mtb clinical isolates in ex vivo culture, and the acid-fast Mtb loads in the cells were analyzed. Immunofluorescent staining and the examination of cytological and histological preparations by confocal microscopy were applied to detect Mtb ligands and macrophage surface markers. Results: The studies shown the lack of Mtb uptake by patients' alveolar macrophages during experimental infection with highly virulent Mtb clinical isolates containing pathogen-associated molecular patterns lipoarabinomannan and Ag38 at all used multiplicity of infection including a very high dose of infection. This fact was probably determined by the absence of pattern recognition receptors CD14, TLR2, and CD11b on the plasma membrane of human cells, likely, as a result of cellular processing from the resected lung tissues of patients. Conclusion: The findings indicate that alveolar macrophages with single Mtb or Mtb in colonies, including those with cord-morphology, found in the ex vivo cell cultures of all TB patients examined, were isolated from the lungs, and they characterize the Mtb infection in patients at the time of surgery.
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Plasma levels of tumor necrosis factor-alpha, interferon-gamma, inducible nitric oxide synthase, and 3-nitrotyrosine in drug-resistant and drug-sensitive pulmonary tuberculosis patients, Ibadan, Nigeria p. 185
Elizabeth Bosede Bolajoko, Olatunbosun Ganiyu Arinola, Georgina Njideka Odaibo, Mamoudou Maiga
DOI:10.4103/ijmy.ijmy_63_20  PMID:32474541
Background: Nigeria is one of the countries with a high burden of tuberculosis (TB) in the world. TB associated inflammation is reported to be central to progression from latent TB to active TB or drug sensitive TB (DSTB) to drug resistant TB (DRTB). Inflammatory cytokines, especially interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), act synergistically in the control of TB infection. They activate macrophages to produce effector molecules such as inducible nitric oxide synthase (iNOS), nitric oxide, and ultimately 3-nitrotyrosines(3-NTs), which are involved in the control of TB. This study investigated the potential involvement of TNF-α, IFN-γ, iNOS, and 3-NT in differentiating DRTB and DSTB in Ibadan, Nigeria. Methods: One hundred participants above 18 years were recruited into this study and were grouped as follows: 32 DRTB, 34 DSTB, and 34 apparently healthy controls. Plasma from the patients was used for the analyses of inflammatory (TNF α and IFN-γ) and oxidative stress (iNOS and 3-NT) biomarkers using the ELISA. Mann–Whitney test was applied for the statistical test. Results: Mean levels of plasma TNF-α, IFN-γ, iNOS, and 3-NT were higher in DRTB (19.74 ± 3.62 pg/mL, 4.41 ± 0.96 pg/mL, 1791.07 ± 419.42 pg/mL, and 20.27 ± 1.80 ng/mL, respectively) and DSTB (17.02 ± 1.84 pg/mL, 5.59 ± 1.40 pg/mL, 2823.42 ± 685.32 pg/mL, and 25.06 ± 2.15 ng/mL, respectively) compared with controls (12.18 ± 0.92 pg/mL, 1.58 ± 0.21 pg/mL, 1275.86 ± 166.12 pg/mL, and 19.98 ± 1.23 ng/mL, respectively). In addition, higher plasma levels of IFN-γ (P > 0.05), iNOS (P > 0.05), and 3-NT (P < 0.05) were observed in DSTB compared with DRTB patients. Conclusion: The 3-NT may be used as differentiating markers of DSTB from DRTB.
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Fungal isolates findings of sputum samples in new and previously treated cases of pulmonary tuberculosis in dr. soetomo hospital surabaya, Indonesia p. 190
Soedarsono Soedarsono, Yuyus Dwi Prasetiyo, Ni Made Mertaniasih
DOI:10.4103/ijmy.ijmy_1_20  PMID:32474542
Background: Fungal infections generally occur in immunosuppressive patients. Long-term tuberculosis (TB) treatment facilitates the occurrence of fungal infections, such as long-term antibiotics administration which is immunosuppressive agents and increases the opportunity of infections. Other factors may be correlated with fungal infection such as age, sex, malnutrition, smoking, diabetes mellitus, lung lesion severity, and the presence of multidrug-resistant TB. This study aims to identify and analyze the proportion of fungal isolates findings in the sputum of new and previously treated cases of pulmonary TB patients. Methods: This was an observational analytic study with a cross-sectional design of all pulmonary TB patients who were hospitalized in Dr. Soetomo Hospital Surabaya. Sputum samples were inoculated on Sabouraud's dextrose agar medium. The growth of visible colonies was identified by Lactophenol Cotton Blue staining using direct microscopy. Results: Fungal isolates were found in 148/193 (77%) pulmonary TB patients. Candida species was found 99% among 148 fungal positive culture. Candida albicans was the most common found fungal species (54.05%), followed by Candida sp (26.35%), Candida glabrata (10.13%), Candida krusei (5.4%), and Candida tropicalis (1.35%). Previously treated cases, sex, malnutrition, and smoking were variables correlated with fungal isolates finding with P value of 0.015, 0.006, 0.010, and <0.001, respectively. Conclusion: The proportion of fungal positive cultures in previously treated cases was higher than in new cases. C. albicans was the most common fungal species both in previously treated cases and new cases of pulmonary TB.
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Antitubercular compounds isolated and characterized in Tithonia diversifolia and Couroupita guianensis p. 195
Nivedita Priyadarshini, Aranganathan Veeramani
DOI:10.4103/ijmy.ijmy_24_20  PMID:32474543
Background: Tuberculosis (TB) has become a public health challenge in the current scenario with a single causative agent, Mycobacterium tuberculosis (MTB) causing the highest morbidity and mortality affecting almost 1.7 million of the population. Furthermore, there has been no novel drug discovery for the past five decades, and the emergence of latent, multiple drug-resistant, and extensively drug-resistant species has given rise to an alarming necessity for a novel compound/s for treating this highly untamable microbe. In developing countries, plant-based drugs have shown promising results in combating TB or its symptoms; naturally occurring secondary metabolites can act as lead-drug molecules or can be co-administered with conventional drugs. Therefore, the present study was focused to identify and characterize potential antimycobacterial compounds found in the screened ethnobotanical plants, Tithonia diversifolia (TD) and Couroupita guianensis (CG). These plants are used for treating respiratory disorders and allergies in the traditional medicinal systems. Methods: These plant leaf extracts were detected and purified using chromatographic techniques for potent antitubercular phytochemicals, and the purified eluents were tested on Mycobacterium smegmatis (MSM) as a surrogate for MTB; further, the fractions inhibiting growth of MSM were characterized through gas chromatography–mass spectrometry. A toxicity test of the purified samples was also assessed by an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and hemolytic assays. Results: The analyzed plant extracts showed the presence of a C-15 sesquiterpene, zingiberene in TD, and a phthalate ester, bis (2-ethylhexyl) phthalate, in CG leaf extracts. The toxicity assessment proved the purified fractions to be moderately toxic at higher concentrations (≥100 μg/mL). Conclusion: Therefore, the identified compounds can be promising antitubercular agents; however, further in vivo investigations will add substantial value to the compounds being pharmacologically useful.
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Tuberculin reactivity in schoolchildren, Kassala State, Sudan p. 200
Fatima Abbas Khalid, Muataz Mohammed Eldirdery, Mamoun El-Obeid El-Gasim, Maowia Mohammed Mukhtar
DOI:10.4103/ijmy.ijmy_16_20  PMID:32474544
Background: Tuberculin skin test (TST) is widely used for the assessment of Bacillus Calmette–Guérin (BCG) vaccine efficacy and screening of latent TB infection (LTBI). Poor or no data are available on the reactivity of tuberculin in Kassala State. The aim of the present study was to assess the response to the BCG vaccine and to estimate the prevalence of LTBI and the annual rate annual risk of tuberculous infection (ARTI) among vaccinated school children using TST. Methods: School-based cross-sectional study was conducted in three localities of Kassala State during 2016–2018. A cluster random sampling method was used for the enrolment. Five tuberculin units of 0.1 mL were injected intradermally in the left forearm of 2568 school children aged 5–15 years. The test was performed after the assessment of child health, nutrition status, and BCG scar status. Tuberculin reaction size was interpreted after 48–72 h. The collected data were analyzed using SPSS (v 20). The classical method was used to estimate ARTI. Results: Overall, there was no reaction in 81.5% of children. Only 0.66% of children had induration 10 mm–28 mm, indicating the prevalence of latent TB with an annual risk of 0.1%. Tuberculin reactivity was statistically significant affected by child age, gender, geographical location, and nutrition status (P < 0.05), whereas BCG scar status had no effect (P > 0.05). Conclusion: The study documented a high proportion of tuberculin nonreactivity irrespective of BCG vaccination status and provides data on the prevalence of latent infection among studied groups. Further studies are needed to address the reasons of low and nonreactivity of tuberculin, and evaluation of the BCG vaccine is recommended.
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Occurrence of Venous Thromboembolism in Hospitalized Patients with Tuberculosis in Saudi Arabia: A Retrospective Cohort Study p. 205
Talal A Altuwaijri, Ghada K Alhindi, Noha M Al-Qattan, Sara K Alkharashi, Ali M Somily, Abdulmajeed H Altoijry
DOI:10.4103/ijmy.ijmy_28_20  PMID:32474545
Background: The purpose of this study was to assess the risk of venous thromboembolism (VTE) and the potential need for thromboprophylaxis in patients with tuberculosis (TB). Methods: A total of 103 patients who underwent treatment for TB at the King Khalid University Hospital in Riyadh between February 2015 to May 2018, the percentage of patients diagnosed with TB who developed VTE was assessed. This was a retrospective cohort study conducted at King Khalid University Hospital in Riyadh. Fisher's exact test was used to analyze the categorical variables.P < 0.05 was considered statistically significant. Results: Our data showed the prevalence of VTE in TB patients to be 2.93% (3/103). VTE occurred irrespective of the type of TB (pulmonary and/or extrapulmonary). All TB patients with VTE showed no significant association with factors such as human immunodeficiency virus coinfection, malignancy, and multidrug-resistant TB. Conclusion: Our study showed that TB patients in Saudi Arabia may be at a higher risk for developing VTE and should be carefully monitored as potential candidates for additional thromboprophylaxis; further studies are recommended to establish more reliable assessment and recommendations.
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Clinicobacteriological evaluation of leprosy patients with 1–5 skin lesions p. 209
Amir Shahid Ansari, Kshitij Saxena, Kaushal Kumar Singh, Anshul Choudhary, Anukriti Singh, Aditya Kumar Tripathi, Vichitra Sharma
DOI:10.4103/ijmy.ijmy_7_20  PMID:32474546
Background: Mycobacterium leprae is a noncultivable mycobacteria, and diagnosis of the disease is based on its clinical and histopathological characteristics and finding the bacteria in skin scrapings and in biopsies taken from the patients. The aim of this study was to shed light on the clinical classification (based on the number of skin lesions) used extensively in the field where patients classified as paucibacillary (PB) were positive on skin smears and histopathology leading to treatment failure and drug resistance. Methods: In this study, we enrolled untreated 62 leprosy patients with 1–5 skin lesions and did a detailed bacterio-histopathological analysis by slit-skin smears (SSSs) and histopathology. Results: Of 62 patients analyzed, 15 patients came out to be multibacillary (MB) and 47 were PB by SSS and histopathology. Conclusion: The findings of the present study showed that the WHO classification of leprosy based on the number of lesions seems to be inappropriate as it considers a number of MB lesions as PB only, thus misleading the treatment strategies. Hence, it is essential that a comprehensive clinicobacteriological assessment of leprosy cases should be done to ensure the appropriate bacillary status and guiding the appropriate treatment strategy.
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Mutation in atpE and Rv0678 genes associated with bedaquline resistance among drug-resistant tuberculosis patients: A pilot study from a high-burden setting in Northern India p. 212
Binit Kumar Singh, Manish Soneja, Rohini Sharma, Jigyasa Chaubey, Parul Kodan, Pankaj Jorwal, Neeraj Nischal, Shivani Chandra, Ranjani Ramachandran, Naveet Wig
DOI:10.4103/ijmy.ijmy_30_20  PMID:32474547
Background: Mutations in atpE gene or transcriptional repressor Rv0678 gene associated with inhibition of adenosine 5′-triphosphate synthase and upregulation of efflux pumps, respectively, may potentially lead to in vitro resistance to bedaquiline. This is the first study from India, which looks at mutations associated with this novel drug. Methods: In 2019 (January to June), a total of 68 laboratory-confirmed pre-extensively drug-resistant tuberculosis (XDR-TB) (fluoroquinolone resistant [n = 52] and second-line injectables resistant [n = 12]) and 4 × DR-TB culture specimens were included. All specimens were evaluated for genetic analysis using predesigned primers of atpE and Rv0678 genes. Results: Among the pre-XDR-TB isolates (n = 64), there were no mutations found in either atpE or Rv0678. However, among the XDR-TB isolates (n = 4), one specimen (25%) was found to be associated with a mutation in atpE gene at position 49, resulting in the amino acid leucine replaced by proline (L-49-P). No mutations were observed with the Rv0678 gene. Conclusion: In this study, genetic analysis showed that only one-fourth XDR-TB isolates had a mutation in the atpE gene; there were no other mutations found in the Rv0678 gene. To the best of our knowledge, this novel mutation (L-49-P) in atpE gene is being reported for the first time in northern India.
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CASE REPORTS Top

Myelofibrosis: An unusual presentation of disseminated tuberculosis p. 216
Neha Sharma, Siddharda Venkat Bikkina, Monica Gupta, Anita Tahlan
DOI:10.4103/ijmy.ijmy_4_20  PMID:32474548
Disseminated tuberculosis (DTB) often presents with protean clinical manifestations that often leads to potential diagnostic dilemmas. The nonspecific features may include pyrexia of unknown origin, hepatosplenomegaly, lymphadenopathy, meningitis, and a variety of hematological abnormalities, namely anemia, pancytopenia, and leukemoid reaction. Tuberculosis is one of the nonhematopoietic diseases that has been reported in conjunction with myelofibrosis. We, hereby, report a case of DTB with massive splenomegaly, severe pancytopenia, and marrow fibrosis.
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Tuberculous verrucosa cutis with a sporotrichoid distribution p. 220
Khushboo Arora, Aditi Dhanta, Naveen Kumar Kansal, Prashant Joshi
DOI:10.4103/ijmy.ijmy_19_20  PMID:32474549
Tuberculosis verrucosa cutis (TBVC) is a common paucibacillary form of cutaneous tuberculosis caused by exogenous reinfection in previously sensitized individuals. The typical morphology is usually observed as a single verrucous plaque with inflammatory borders mostly on the hands, knees, ankle, and buttocks; however, several atypical morphologies of the lesions have also been described. TBVC occurring in sporotrichoid pattern is relatively rare. We report a case of a rare sporotrichoid presentation of TBVC in a 38-year-old male patient in the absence of any primary tuberculous focus.
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Long-term ulcerations caused by Mycobacterium lepromatosis p. 223
Ilaria Trave, Gianfranco Barabino, Alberto Cavalchini, Aurora Parodi
DOI:10.4103/ijmy.ijmy_40_20  PMID:32474550
Patients with leprosy rarely present ulcerated lesions that can appear during reactional states like Lucio's phenomenon (LP), as in our case. LP is a rare complication of multibacillary leprosy due to massive bacilli invasion of endothelial cells causing a thrombotic syndrome. The initial macular lesion is purpuric followed by multiple infiltrated papules and nodules, some of them ulcerated, associated to loss of sensation on lower limbs. The importance of recognizing ulcers as a specific cutaneous manifestation of leprosy allows early diagnosis and treatment, and therefore avoiding the development of disabilities and persistence of illness. Infection by Mycobacterium lepromatosis is associated with LP and it should be especially sought in patients from endemic areas.
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Late leprosy reaction presenting as erythema multiforme-like erythema nodosum leprosum with underlying rifampicin resistance and its potential implications p. 226
Kabir Sardana, Anita Kulhari, Sinu Rose Mathachan, Ananta Khurana, Prekshi Bansal, Arvind Ahuja, Mallika Lavania, Madhvi Ahuja
DOI:10.4103/ijmy.ijmy_26_20  PMID:32474551
Erythema multiforme (EM)-like erythema nodosum leprosum (ENL) is a rare atypical presentation, and its late appearance after the completion of multidrug therapy (MDT) is unusual. We describe the case of a lepromatous leprosy patient who after the completion of MDT presented to us with late EM-like ENL and was found to be resistant to rifampicin. We discuss the implications of this finding and the potential role of resistant bacilli in causing reactions with atypical presentations.
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LETTER TO EDITOR Top

Kudoh swab method for Mycobacterium tuberculosis culture: Looking back to the 70s to fight tuberculosis p. 229
Miguel Angel Garcia-Bereguiain
DOI:10.4103/ijmy.ijmy_66_20  PMID:32474552
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