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   Table of Contents - Current issue
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January-March 2022
Volume 11 | Issue 1
Page Nos. 1-131

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ORIGINAL ARTICLES  

Digital health interventions in the clinical care and treatment of tuberculosis and hiv in central Ethiopia: An initial provider perceptions and acceptability study using the unified theory of acceptance and use of technology model Highly accessed article p. 1
Emnet Getachew, Yimtubezinash Woldeamanuel, Tsegahun Manyazewal
DOI:10.4103/ijmy.ijmy_235_21  PMID:35295017
Background: Digital health technologies are emerging as promising technologies to advance clinical care. This study aimed to assess providers' perceptions and acceptability of digital health interventions (DHIs) in the clinical care and treatment of tuberculosis (TB) and HIV in Addis Ababa, Ethiopia. Methods: This was a multi-center, facility-based, mixed-method, cross-sectional study that included 14 government health-care facilities. The participants were health-care providers (HCPs) who provide TB and HIV clinical care. Using a tool framed by the unified theory of acceptance and use of technology model, data were collected. A linear regression model was used to assess the relationship between dependent and independent variables. Results: There were 76 HCPs actively engaged in HIV/TB clinical care services in the selected 14 study sites, of whom 60 met the inclusion criteria and participated in this study. The major factors that influence HCPs' willingness to use different technologies were educational level (β = 0.097, t = 3.784, P = 0.006), age (β = −0.227, t = −1.757, P = 0.027), work experience (β = −0.366, t = −2.855, P = 0.016). The strongest facilitator of their acceptance and the use of the digital adherence technology were perceptions of positive performance expectancy. Conclusion: Many public healthcare facilities in Addis Ababa have already begun the process of implementing various DHIs and the level of acceptability of these technologies by HCPs was found to be high.
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Early secreted antigenic target of 6 kda-like proteins of mycobacterium tuberculosis: Diagnostic and vaccine relevance p. 10
Abu Salim Mustafa
DOI:10.4103/ijmy.ijmy_232_20  PMID:35295018
Background: Early secreted antigenic target of 6 kDa (ESAT6) is low-molecular-weight and immunodominant protein of Mycobacterium tuberculosis with relevance to diagnosis and vaccine development. Analysis of the M. tuberculosis genome has shown the existence of 23 ESAT6-like genes. This study was aimed to determine M. tuberculosis-specificity vis-à-vis crossreactivity of ESAT6-like genes and encoded proteins and their potential in the diagnosis and vaccine development. Methods: All ESAT6-like proteins were characterized using the webserver Tuberculist. The sequence identities were determined using basic local alignment search tool. Results: The genes for six ESAT6-like proteins were located in M. tuberculosis-specific genomic regions of differences (RDs), i.e., EsxA and EsxB in RD1, EsxO and EsxP in RD7, and EsxV and EsxW in RD9. The genes for other ESAT6-like proteins were located in the genomic regions shared with other mycobacteria. Based on sequence identities, the ESA6-like proteins were divided into four subfamilies of 15 proteins and no subfamily of 8 proteins. The members of subfamilies 1-4 shared extensive sequence identities among the members of each subfamily. Each member of subfamily 1 (EsxI, EsxL, EsxN, EsxO, EsxV) and subfamily 2 (EsxJ, EsxK, EsxM, EsxP, EsxW) were homologs. Hence, the gene sequences identical to EsxO and EsxP located in RD7, and EsxV and EsxW located in RD9 were also present in the regions of M. tuberculosis genome shared with other mycobacteria. Conclusion: Because of their specificity to M. tuberculosis, only EsxA (ESAT6) and EsxB (CFP10) will be useful in the specific diagnosis. However, other ESAT6-like proteins may be useful for vaccine development against tuberculosis.
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Multimorbidity among persons living with human immunodeficiency virus in a moroccan referral hospital p. 16
Hicham Titou, Hasna Kerrouch, Mohammed Boui, Naoufal Hjira
DOI:10.4103/2212-5531.307070  PMID:35295019
Background: Multimorbidity is the co-existing of two or more chronic health conditions in addition to human immunodeficiency virus (HIV). In Morocco, the prevalence of and factors associated with multimorbidity in HIV-infected patients have not been well-documented. Methods: This cross-sectional analysis was conducted in 2018 and included 269 HIV-infected patients. Medical records were reviewed to identify chronic health conditions and to rate multimorbidity using the Cumulative Illness Rating Scale (CIRS). Associations between a higher CIRS score and risk factors were assessed using linear regression. Results: The mean age was 48.9 ± 10.7 years with a male predominance (75.5%). One in 5 (20,8%) had ever been diagnosed with acquired immunodeficiency syndrome. More than a 3rd (34.8%) of the patients had two or more chronic health conditions in addition to HIV. The most frequently documented comorbidities were metabolic complications followed by vascular disease. In multivariate analysis, older age, male gender, duration of receiving antiretroviral therapy, taking indinavir-containing antiretroviral regimen, having ever been stage Centers for Disease Control and Prevention B or C, and current viral load ≥50 copies mL–1 were associated with a higher CIRS score. Conclusion: The prevalence of comorbidities is substantially high. Care models for people living with HIV should include assessing and managing multimorbidity, particularly in patients who present with these associated factors.
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Validation and comparative analysis of kogene mycobacterial interspersed repetitive unit-variable number of tandem repeat typing kit and its application on clinically isolated mycobacterium tuberculosis samples from national tuberculosis hospital, Republic of Korea p. 23
Jihee Jung, Taeuk Kang, Yoohyun Hwang, Sungweon Ryoo
DOI:10.4103/ijmy.ijmy_8_22  PMID:35295020
Background: Tuberculosis (TB) remains a serious public health burden in Korea. Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) is preferred for epidemiological TB investigation. Until recently, the difficulty lies in epidemiological TB investigation due to the absence of commercialized MIRU-VNTR in Korea. Here, we have evaluated the newly designed MIRU-VNTR kit by Kogenebiotech, Korea. Materials and Methods: A total of 200 samples, where 100 are Mycobacrerium tuberculosis (M. tuberculosis), and the other 100 are non-M. tuberculosis, were used. Initially, the Kogenebiotech MIRU-VNTR typing kit (KoMIRU) was compared with Multilocus Variable Number Tandem Repeat Genotyping of M. tuberculosis typing kit (MVNTR) by Philip Supply for validation purpose. Then, Limit of Detection for DNA copies was optimized. Finally, KoMIRU and Genoscreen MIRU-VNTR typing kit (GeMIRU) were tested and comparatively analyzed for its specificity and sensitivity. Results: The study showed that the KoMIRU has slightly higher discriminatory power over MVNTR, 100% versus 97.5%. In comparative analysis, the KoMIRU has shown comparable capability as GeMIRU, showing 100% for sensitivity and specificity with a 95% CI value of 96.38 to 100.00%. Also, no discrepancies were observed on discriminated lineage strains between KoMIRU and GeMIRU. Out of 100, 84 were identified as Beijing strains, and remains were identified as NEW-1 (n = 8), Uganda (n = 6), East African Indian (EAI) (n = 6), Turkey (n = 2), and Haarlem (n = 1). Conclusion: In this study, KoMIRU has shown a comparable capability to GeMIRU. Furthermore, previous researches had suggested an association between lineage strains and drug resistance; hence, the implementation of KoMIRU can help in TB control and prevention.
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Uncommon manifestations in tuberculosis: An expanding clinical spectrum from North India p. 30
Jitendra Singh, Anju Dinkar, Poonam Gupta
DOI:10.4103/ijmy.ijmy_242_21  PMID:35295021
Background: Despite being given the best by the health department to eradicate the disease, an alarming rise of tuberculosis (TB) remains a significant public health concern in India. Recently, highly variable clinical manifestations of TB have been reported. This study highlights the unusual presentations of TB with a comprehensive overview of epidemiology, demography and risk factors in the expended clinical spectrum of TB patients and their outcomes. Methods: It is a retrospective study using the records of 503 TB patients of all age groups of either sex from July 2017 to January 2021 at two tertiary care hospitals in North India. Results: Out of 503 cases, pulmonary, extrapulmonary, and disseminated TB were 77.7%, 19.5%, and 2.8%, respectively. Among all TB cases, 36 (7.2%) had uncommon manifestations, including the most common was pyrexia of unknown origin in 12 (33.3%) cases and liver abscess in 5 (13.9%) cases, followed by pancytopenia in 4 (11.1%) cases and chyluria in 3 (8.3%) cases. Atypical skin nodules and multiple swellings were also noted in three (8.3%) cases. Male sex (58%) and rural area (66.7%) were dominant in TB with uncommon manifestation (TBU) cases. The mean age in TBU cases was 46.92 years, whereas 34.26 years in all TB cases. It was extremely significant. The statistically significant risk factors in the TBU case were low socioeconomic status (24, 66.7%), inadequate nutrition (11, 30.6%), and smoking (19, 52.8%). Conclusions: Early recognition of uncommon presentations is imperative to respond better.
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Predictors of treatment outcomes in drug resistant tuberculosis-observational retrospective study p. 38
July Mary Johnson, Aswini Kumar Mohapatra, Saleena Ummer Velladath, Kavitha S Shettigar
DOI:10.4103/ijmy.ijmy_244_21  PMID:35295022
Background: In this study, we evaluate the predictors of treatment outcomes in drug resistant tuberculosis. Methods: An observational retrospective study was conducted by using the medical records of patients confirmed for TB at Kasturba Medical College from January 2015 to December 2018. Results: Four hundred and sixty-two TB patients were included in this study. Of the total TB-confirmed patients, about 85.1% are diagnosed with pulmonary TB (PTB) (n = 393), 11.7% were extrapulmonary tuberculosis (EPTB) (n = 54), and 3.2% (n = 15) cases had both PTB and EPTB. Among the 462 cases, the frequency of multidrug-resistant TB (MDR-TB) was 25% (n = 117), extensively drug-resistant TB was 1% (n = 3), and non-MDR cases were 74% (n = 342). The frequency of unsuccessful treatment outcome was 92.9% (n = 429) and successful outcome was 7.1% (n = 33). There were 68.2% of new and 31.8% retreatment cases of TB. HIV co-infection was found in 2.3% (n = 14) of TB cases, and among them, 64.3% (n = 9) were found in PTB cases. The major comorbidities found were diabetes (21.2%), weight loss (12.6%), and anemia (12.6%). There was a difference in rate of PTB cases across years decreasing in the year 2017, whereas ETB cases were increasing in the year 2017. The TB treatment success rate was increased from 2015 (4.8%) to 2018 (8.3%). Conclusion: The higher rate of poor treatment outcome emphasizes the need of improvement in TB surveillance, treatment, more stringent follow-up, monitoring, and patient education to ensure complete and successful treatment.
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The real burden of tuberculosis: Hidden cases diagnosed on autopsy at a tertiary care center of India p. 47
Swapnil Agarwal, Zini Chaurasia, Dishant Kumar Malik, Renu Gupta, Cheta Singh, Surbhi Jain
DOI:10.4103/ijmy.ijmy_227_21  PMID:35295023
Introduction: Developing nations have a huge burden of tuberculosis (TB), because of which many cases are undetected and diagnosed only on autopsies. The purpose of this study was to find these cases in a series of consecutive autopsies conducted at a tertiary care centers. Materials and Methods: This retrospective study of 7-year duration from 2014 to 2020 consisted of reviewing 767 autopsies. The records of cases where a diagnosis of TB were established on histopathology were noted and evaluated. Results: Of 767 autopsies, TB was the diagnosis on histopathology in 72 cases. Of the 72 cases, 53 cases were undiagnosed antemortem and incidentally detected on autopsy. The study showed a male predominance with a 1.52:1 male-to-female ratio. The most common age group involved was the second decade. The study constitutes 26 cases of isolated pulmonary TB, 23 cases of disseminated TB, three cases of solitary renal TB, and one case of hepatic TB. The liver was the most commonly involved organ along with the lung in cases of disseminated TB, followed by the spleen, kidney, pancreas, intestine, brain, and heart. Discussion: Epidemiology and research on TB may be affected by these hidden cases which are unraveled incidentally on autopsy. These cases must always be reported and brought to the attention of clinicians for nation's better public health.
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Molecular detection of mycobacterium tuberculosis complex species in triatomines found in urban households and Peridomiciles in a city with high prevalence of tuberculosis in Northeastern Brazil p. 51
Caroliny Soares Silva, Luana Nepomuceno Gondim Costa Lima, Karla Valéria Batista Lima, Rosa Livia Freitas de Almeida, Marília Lima da Conceição, Cynara Carvalho Parente, Amanda Albuquerque Rocha, Thales Candido da Silva, Soraya de Oliveira Sancho, Cristiane Cunha Frota
DOI:10.4103/ijmy.ijmy_230_21  PMID:35295024
Background: Triatomine insects, native to northeastern Brazil, have been found in the urban peridomicile. The city of Sobral has a high number of tuberculosis cases and several triatomine species. This study investigates the presence of mycobacteria, particularly Mycobacterium tuberculosis complex (MTBC) species, in triatomines captured in the urban perimeter of Sobral. Methods: We analyzed 167 triatomines captured in urban households and peridomiciles of Sobral. Mycobacteria were identified by the PRA-hsp65 method followed by partial sequencing of the hsp65 and rpoB genes. The sequences confirmed as MTBC were also typed by mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and spoligotyping. Results: Triatoma brasiliensis (38.6%), Triatoma pseudomaculata (32.9%), Panstrongylus lutzi (24.3%) were the most frequently identified. In 51.1% (70/167) of them, species of the Mycobacteriaceae family were detected by PRA-hsp65; of these, 31.4% (22/70) were identified as belonging to MTBC species. Nine (12.9%) of the triatomine samples were confirmed by sequencing as belonging to MTBC species. MIRU-VNTR genotyping suggests that the presence of different MTBC sublines in the triatomines should be investigated. Conclusion: This is the first report of MTBC lineages in triatomine insects. These results indicate the migration and adaptation of these insects in an urban setting.
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Genetic diversity of nontuberculous mycobacteria among symptomatic tuberculosis negative patients in Kenya p. 60
Zakayo Maingi Mwangi, Nellie Njambi Mukiri, Frank Gekara Onyambu, Bulimo Dimbuson Wallace
DOI:10.4103/ijmy.ijmy_224_21  PMID:35295025
Background: Non-Tuberculous Mycobacteria (NTM) transmission to humans occurs through inhalation of dust particles or vaporized water containing NTM leading to pulmonary manifestations. NTM infections are often misdiagnosed for tuberculosis (TB) due to their similar clinical and radiological manifestations. Aims and Objectives: We, therefore, performed a species-level identification of NTM in symptomatic TB negative patients through sequencing of the hsp65 gene. Materials and Methods: We conducted a cross-sectional study at the National Tuberculosis Reference Laboratory in the period between January to November 2020. One hundred and sixty-six mycobacterial culture-positive samples that tested negative for TB using capilia underwent Polymerase Chain Reaction targeting the hsp65 gene. Isolates showing a band with gel electrophoresis at 441 bp position were sequenced using Sanger technology. Geneious software was used to analyze the obtained sequences, and the National Center for Biotechnology Information gene database identified NTM species for each isolate. A phylogenetic tree was constructed from the DNA sequences and evolutionary distances computed using the general time-reversible method. Pearson chi-square was used to determine the association between NTM infection and participants' characteristics. Results: Our study identified 43 different NTM species. The dominant NTM belonged to Mycobacterium avium complex 37 (31%). Slow-growing NTM were the majority at 86 (71%) while rapid-growing NTM were 36 (29%). A significant association (P<0.05) was observed for regions and age, while patient type had a weak likelihood of NTM infection. Conclusion: Our study characterized the diversity of NTM in Kenya for the first time and showed that species belonging to M. Avium Complex are the most prevalent in the country.
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Changes of th1 and th2 cytokines levels among sudanese tuberculosis patients during treatment p. 70
Ahmed A Abdul-Aziz, Mogahid M Elhassan, Amjad M Yousuf, Mohamed E Hamid, Salma A Abdulsalam, Rana A Gafar, Miskelyemen A Elmekki
DOI:10.4103/ijmy.ijmy_245_21  PMID:35295026
Background: The interaction of T cells with infected macrophages depends on the interplay of cytokines produced in each cell, and this mechanism is a key to protective immunity against Mycobacterium tuberculosis. Extensive research has been devoted to studying the changes in systemic cytokine levels in patients with tuberculosis (TB), but the results are inconclusive. Determine Th1 and Th2 cytokine immune response levels among new TB patients compared to follow-up and healthy control. Design: Cross-sectional laboratory-based study. Setting: Immunology Laboratory, National Center for Research. Methods: Blood samples (n = 145) were collected from confirmed new TB cases, follow-up TB cases, and from healthy controls. Participants were initially diagnosed by microcopy using Ziehl–Neelsen smear method and confirmed by polymerase chain reaction using IS6110. Cytokine levels (interleukin-10 [IL-10], tumor necrosis factor alpha [TNF-α], and Interferon-gamma [IFN-γ]) were measured directly from plasma using sandwich enzyme-linked immunosorbent assay. Main Outcome Measures: Measuring Th1 cytokines (IFN-γ and TNF-α) and Th2 cytokine (IL-10). One hundred and forty-five cases (new TB cases, 85; follow-up, 25; and healthy control, 35) were included in this study. Results: The study population were mainly males (70.3%) compared to females (29.7%) and 87.5% aged between 21 to 60 year. The plasma IFN-γ levels were found significantly higher in new TB cases (mean 35.38 pg/m; confidence interval: 29.32–41.43) than in the follow-up patients and the healthy control (P = 0.000). There were no significant differences in TNF-α and IL-10 levels among the new TB cases and the follow-up and healthy control (P = 0.852 and P = 0.340, respectively). Conclusions: Direct plasma IFN-γ level can be used in TB patient follow-up as a recovery marker as it correlated well with the appearance of the disease and treatment response.
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Clinical profile, diagnosis, treatment, and outcome of patients with tubercular versus nontubercular causes of spine involvement: A retrospective cohort study from India p. 75
Nitin Gupta, Shyamasunder N Bhat, Suhas Reddysetti, MA Afees Ahamed, Divya Jose, Aravind Srivatsa Sarvepalli, Sowmya Joylin, Vishwapriya M Godkhindi, Ali A Rabaan, Kavitha Saravu
DOI:10.4103/ijmy.ijmy_243_21  PMID:35295027
Background: In tuberculosis (TB) endemic areas, other pyogenic causes of spine involvement may be missed. The study aimed to describe TB and non-TB causes of spine involvement and identify features that can help in differentiating them. Methods: A retrospective cohort study was conducted to screen the clinical records of all admitted patients (Kasturba Hospital, Manipal) in 2018–20 for a diagnosis of spondylitis and/or sacroiliitis. The clinical features, radiological findings, laboratory parameters, treatment details, and outcomes were compared among those diagnosed with confirmed TB, confirmed brucellosis, or confirmed pyogenic infection. A scoring system was also developed to differentiate spondylodiscitis due to tuberculous and pyogenic causes. The qualitative variables were compared using the Chi-square test, while quantitative variables were compared using the one-way analysis of variance test. Results: Of 120 patients with spine infections, a total of 85 patients were confirmed with the microbiological diagnosis of interest. Involvement of the thoracic spine, longer duration of illness, and caseous granulomatous reaction on histopathology was more common in TB patients. Male gender, involvement of lumbar vertebra, and neutrophilic infiltrate on histopathology were more common in brucellosis patients. Male gender, diabetes mellitus, involvement of lumbar vertebra, neutrophilic infiltrate on histopathology, leukocytosis, and increased C-reactive protein were more commonly seen in patients with pyogenic infection. The scoring system had a sensitivity and specificity of 75% and 91%, respectively, when used to differentiate TB from pyogenic infection. Conclusions: In resource-limited settings, suggestive findings can be used to decide empiric therapy.
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Investigation of two general venous thromboembolism risk-stratification models in predicting venous thromboembolic events in TB patients p. 83
Babak Sharif-Kashani, Mojdeh Azimi, Payam Tabarsi, Makan Sadr, Shahriar Shirzadi
DOI:10.4103/ijmy.ijmy_252_21  PMID:35295028
Background: Tuberculosis (TB) remains an infectious disease with a high prevalence worldwide and represents a major public health concern. It is known that TB causes a hyper-coagulable state due to its infective nature. Thus, patients are prone to higher incidence rates of venous thromboembolism (VTE) in comparison with the general population. Although there are many risk assessment models (RAMs) that estimate the risk of VTE incidence in the general population, none have been proven to show significant prognostic value in early and accurate VTE prediction among TB patients. This study aims to investigate the accuracy of general RAMs in prediction of VTE incidence in the population of TB-positive patients. Methods: The following survey is a retrospective study among patients afflicted with TB, in whom VTE had occurred either during or at the onset of admission. A total number of 865 smear-positive TB cases were recorded in hospital in a 7-year timespan, among which a total sum of 37 patients (67.6% males, age: 56.19 ± 20 years) experienced at least one episode of thromboembolic incidence. We nominated Padua and Geneva RAMs and calculated the scores with regard to their inpatient hospital records. Results: Of 865 adult hospitalized smear-positive TB patients, 37 patients happened to develop VTE in the course of infection, after excluding the unacceptable data. The incidence of VTE was calculated at 4.27%. Of all VTEs, 73% turned out to be deep venous thromboembolism (DVT), 18.9% were pulmonary thromboembolism (PTE), and 8.1% of patients developed both DVT and PTE during the course of disease. Among all cases, 32.4% revealed Geneva score equivalent or >3. It conveys the meaning that these patients were at greater risk for VTE development and were indicated to receive prophylactic medication. Similarly, Padua model was capable of predicting 29.7% cases scoring >4, which is alarming for elevated VTE probability. 21.6% of TB patients, who had developed VTE during the course of their disease eventually passed away. Conclusion: Our statistics show minimal positive predictive value for Padua and Geneva RAMs, which are seemingly in sharp contrast with the excellent validation of these models verified by numerous surveys in general population. This fact could be attributable to failing to consider TB, or in general chronic infections, as independent indicators of VTE incidence. These findings indicate the need for revising the presenting RAMs or establishing a separate RAM for VTE prediction in TB patients, resembling the VTE risk assessment model for cancer patients.
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Spoligotyping and polymerase chain reaction based mycobacterium bovis strains typing with methods (enterobacterial repetitive intergenic consensus-polymerase chain reaction, randomly amplified polymorphic dnas-polymerase chain reaction and out polymerase chain reaction) p. 88
Funda Sahin, Gülnur Tarhan, Halil Cinoglu, Mediha Begüm Kayar, Gülfer Yakici
DOI:10.4103/ijmy.ijmy_253_21  PMID:35295029
Background: In this study, it was aimed to investigate Mycobacterium bovis strains isolated from lungs and lymph nodes of slaughtered animals on clonal level by using different methods such as spoligotyping, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), randomly amplified polymorphic DNAs (RAPD-PCR) and OUT-PCR. Comparative evaluation of these methods was further conducted. Methods: A total of 38 M. bovis isolates were evaluated in the study. DNA isolation of all M. bovis strains isolated from pruvat free Löwenstein Jensen medium was done by boiling method for ERIC-PCR, RAPD-PCR, and OUT PCR. Mickle device was used for DNA isolation for spoligotyping method. Results: In 38 M. bovis isolates examined in our study, 4 different groups were determined by spoligotyping and RAPD-PCR test methods, and 5 different groups were detected in ERIC-PCR tests. In the OUT-PCR tests, the band which provides sufficient type separation was not observed. Conclusion: ERIC-PCR, RAPD-PCR, and OUT-PCR methods are easily applicable, simple, and relatively inexpensive methods for evaluating the differences between origins in the typing of M. bovis. The tests need to be evaluated in more detail with extensive studies.
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Genetic polymorphism of toll-like receptors in HIV-I infected patients with and without tuberculosis co-infection p. 95
Gaurav Kaushik, Richa Vashishtha, Himanshu Tripathi, Raj Narayan Yadav
DOI:10.4103/ijmy.ijmy_4_22  PMID:35295030
Background: Toll-like receptors (TLRs) are identified as one of the key components of innate immune system due to their ability to sense conserved molecular motifs associated with several pathogens. It has been implicated from several evidence that mutations in genes encoding TLRs are associated with increased or decreased susceptibility to various infectious diseases. Methods: The study was prospective, cross-sectional, as well as longitudinal in nature, which includes 223 HIV-positive patients, 150 HIV-positive patients with latent tuberculosis (TB) infection, 150 HIV-positive patients with active TB, 200 HIV-negative newly diagnosed sputum smear positive pulmonary TB patients, and 205 healthy subjects. Results: A statistically significant difference was observed in allelic frequencies of TLR4 between healthy subjects and HIV + TB patients (P < 0.001), healthy subjects, and pulmonary TB (PTB) Category-I patients (P < 0.01) and between healthy subjects and HIV + TB patients (P < 0.001). TLR4 genotype frequencies were also significantly different between healthy subjects and PTB Cat I patients (P < 0.001) and HIV + and HIV + TB patients (P < 0.01). A statistically significant difference was also observed between HIV + and PTB Cat I patients (P = 0.04), HIV + LTBI and HIV + TB patients (P = 0.01), and between HIV + TB and PTB Cat I patients (P < 0.01). Conclusion: This study implicates that Asp299Gly polymorphism in TLR4 gene is associated with increased susceptibility to active TB in HIV-seropositive patients. Increased frequency of 'A' allele in TLR9 gene was also discovered at the time of active TB development in ART naïve HIV + patients, who developed active TB on follow-up.
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Turnaround times of the sputum sample courier system at tuberculosis treatment centers in Lusaka, Zambia, 2021 p. 103
Samuel Daka, Yuko Matsuoka, Masaki Ota, Susumu Hirao, Abraham Phiri
DOI:10.4103/ijmy.ijmy_3_22  PMID:35295031
Background: Health facilities which do not have capacity to diagnose tuberculosis (TB) depend on other facilities. This involves the courier of specimen such as sputum to diagnostic centers. This study was aimed at determining the turnaround time of sputum examinations for TB patients involving a courier system between the treatment and diagnostic centers. Methods: The study tracked the sputum samples between TB treatment and diagnostic centers. Sputum samples for both diagnosis and follow-up reasons were purposely and serially tracked from the time they were sent to the laboratory to the time results were received at the treatment centers. Results: Of the 65 sputum samples tracked at Chazanga, results were available for 49 (75.4%), 6 (9.2%) were unaccounted for, 4 (6.2%) were rejected by the laboratory, 4 (6.2%) had “error” results, and 2 (3.1%) were declared “missing” because it took more than a month to return the results. The turnaround time ranged from 2 days to 18 days with an average of 5.8 days (95% confidence interval [CI]: 4.5–7.1 days). At Kaunda Square, of the 49 samples tracked, results were available for 44 (89.8%), 2 (4.1%) were unaccounted for, 2 (4.1%) were rejected, and 1 (2.0%) was declared “missing.” The turnaround time ranged from 2 to 25 days with an average of 6.3 days (95% CI: 5.3–7.4 days). Conclusion: The turnaround times of sputum examinations of the two treatment centers were long. The courier system should be closely monitored to determine if it is performing well because the system is still necessary for facilities without laboratories.
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Immunotherapeutic potential of n-terminally formylated ESAT-6 protein in murine tuberculosis p. 108
Shabir Ahmad Mir, Sadhna Sharma
DOI:10.4103/ijmy.ijmy_39_21  PMID:35295032
Background: The early secreted antigenic target-6 kDa (ESAT-6) being one of the important antigens expressed by Mycobacterium tuberculosis (MTB) has been widely investigated for its strong immunmodulatory effects. We have previously evaluated the immunotherapeutic efficacy of ESAT-6 in the murine model of experimental tuberculosis (TB). Now in the present study, we have evaluated the immunotherapeutic efficacy of N-terminally formylated form of ESAT-6 (f-ESAT-6) in murine TB. Materials and Methods: The production and purification of f-ESAT-6 have been discussed in our earlier report (Mir SA and Sharma S, 2014). In the present study, the MTB H37Rv-infected mice were treated with f-ESAT-6 alone or in combination with anti-TB drugs (ATDs). Four weeks postinitiation of the treatment, the experimental mice were sacrificed, and the colony-forming units (CFUs) were enumerated in their lungs and spleen as described in “materials and methods” section. Results: The N-terminally formylated ESAT-6 protein (f-ESAT-6) induced a moderate reduction in the bacterial load in the target organs of infected mice. Compared to the dimethyldioctadecyl ammonium bromide treated and untreated groups, the f-ESAT-6 treatment significantly reduced the CFU in the spleen and lungs of infected mice by 0.377 log10 units (P < 0.05) and 0.396 log10 units (P < 0.01), respectively. The administration of f-ESAT-6 in combination with ATDs revealed an additional immunotherapeutic effect and elicited higher therapeutic efficacy over drugs (ATDs) alone. Conclusion: The results of the present study clearly indicate that f-ESAT-6 protein alone as well as in combination with the conventional ATDs induce moderate therapeutic effect against experimental TB.
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CASE REPORTS Top

Pott's disease (tuberculous spondylitis) p. 113
Inês Almeida Pintor, Flávio Pereira, Susana Cavadas, Pedro Lopes
DOI:10.4103/ijmy.ijmy_2_22  PMID:35295033
Pott's disease is a vertebral infection caused by Mycobacterium tuberculosis. Indolent nature and subacute course are associated with late diagnosis. A clinical case is presented whose diagnosis was delayed by atypical presentation with progressive worsening of symptoms. Magnetic resonance imaging (MRI) of the dorsolumbar spine revealed T7–T8 angulation suggestive of secondary injury, with intracanalar extension and spinal cord compression. Gastric aspirate cultures, direct microscopy, and polymerase chain reaction (PCR) were A 79-yearold female came to the emergency department with right back pain, pleuritic, with 12 h of evolution. Anorexia and weight loss,1 month evolution. Computed tomography (CT) of the dorsal spine revealed T7–T8 lytic lesions, suggestive of secondary nature. Objectively:weight loss and pain during thoracic palpation. Annalistically: normocytic/normochromic anemia, hypercalcemia, hepatic cholestasis, C-reactive protein (CRP) 7.12 mg/dL. Chest X-ray and electrocardiogram without alterations. She was admitted in Internal Medicine service. Analytically: hypophosphatemia, parathyroid hormone elevated, CRP 6 mg/dL, Beta-2 microglobulin elevated, dyslipidemia, iron and folicacid deficiency.negative for M. tuberculosis. T8 aspiration CT guided: cultures/direct microscopy negative, PCR positive for M. tuberculosis. Introductionof antitubercular drugs. Worsening of symptomatology, with paraparesia. MRI of the dorsal spine revealed spondylodiscitis and spinal cordcompression in T7–T8. Diagnosis revealed vertebral tuberculosis with spinal cord compression. She was transferred to neurosurgery servicefor surgical treatment. There was clinical and analytical improvement. Draws attention to difficulty in diagnose a treatable disease in a patientwith a rare presentation.
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Assessment of multidrug-resistant tuberculosis patient's skin drug reaction in Zanzibar: A certain causal relationship with Clofazimine p. 116
Saida Abuubakar Mohamed, Julius O Mshana, Khamis Abubakar, Ali Hamid Juma, Issa A Mussa, Mohd Foum Hamad, Juma Khamis Juma, Farhat Jowhar Khalid, Dennis Modestus Lyakurwa
DOI:10.4103/ijmy.ijmy_176_21  PMID:35295034
Drug-resistant tuberculosis (DR-TB) is a serious public health of concern. We present the management of multidrug-resistant (MDR)-TB with skin reaction in Zanzibar in a patient who had prior exposure to anti-TB drugs. The reaction developed 4 months later, following MDR-TB treatment, stopped when the drug was withdrawn, and reappeared when reintroduced. Close monitoring is important in managing DR-TB cases, and an active DR-TB safety, monitoring, and management is required to detect, monitor, and manage adverse events timely.
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Ethambutol-induced bullous skin lesions in mycobacterium kansasii lung infection p. 120
Venkateswara K Kollipara, Mitchell Horowitz, Jeffery Lantz, Stephanie Nagy-Agren
DOI:10.4103/ijmy.ijmy_204_21  PMID:35295035
Mycobacterium kansasii is the second most common cause of nontuberculous mycobacterial (NTM) lung disease after Mycobacterium avium complex infection in the United States.[1] The first-line therapy for M. kansasii is a three-drug regimen including rifampin, isoniazid, and ethambutol. We present a case of a patient with pulmonary M. kansasii who developed bullous skin lesions while receiving this regimen and again after rechallenge with ethambutol. In patients with intolerance to one of the first-line antibiotics, a multidisciplinary team approach to starting second-line agents is needed. Ethambutol should be included in the differential diagnosis of drug-induced bullous skin lesions in treated patients with NTM, who develop new onset rash with blisters or ulceration.
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A rare case of calvarial tuberculosis in post-COVID-19 scenario p. 123
Abhijit Acharya, Atmaranjan Dash, Sarita Otta
DOI:10.4103/ijmy.ijmy_180_21  PMID:35295036
Isolated calvarial involvement with tuberculosis (TB) is a very rare entity, with the incidence of only 0.01% of all patients with mycobacterial infections. The factors attributable could be malnutrition, poor socioeconomic conditions, and immunodeficiency syndromes. We hereby present the case of a 35-year-old male who had recently recovered from coronavirus disease 2019 and a diagnosed case of Evan's syndrome with secondary hemophagocytic lymphohistiocytosis who presented with a scalp swelling on the right frontotemporal region. He presented to the emergency department with acute-onset generalized tonic − clonic seizures with high-grade fever. Clinically, the swelling appeared like a cystic swelling of the scalp. On evaluation, there was a collection present below the scalp communicating with the extradural space, involving the underlying skull bone. The patient was operated with drainage of the abscess plus excision of the pathological underlying skull bone. The pus revealed florid amount of acid-fast bacillus on Ziehl–Neelsen staining. The patient was started on four drugs Category 1 antitubercular regimen. The patient responded well to the combined surgical and medical treatment. It should be emphasized that TB can involve any part of the body. It should be kept as differential diagnosis of any chronic inflammatory lesion involving the bony skeleton, especially in endemic countries where combined surgical and medical treatment is usually sufficient to provide a cure.
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A successful salvage story: Uveitis with nontuberculous mycobacterial infection in a patient on secukinumab p. 126
Rajesh Venkitakrishnan, Leya Sara George, Anabi Shahi, Sheena Liz Mani, Jolsana Augustine, Divya Ramachandran, Anand Vija
DOI:10.4103/ijmy.ijmy_226_21  PMID:35295037
The reported occurrence of ocular infections with nontuberculous mycobacterial (NTM) infections has been increasing in the past few decades. NTM are known to cause intraocular infections as well as infections of the ocular appendages and are often recalcitrant to medical therapy. Uveal involvement due to NTM is rare and most reported cases have predisposing factors such as cataract surgery or immunocompromised states. Diagnosis and treatment pose challenge due to difficulty in procuring sufficient clinical material to obtain microbial diagnosis and inadequate response to medical therapy. The clinical challenge is further heightened in the presence of an underlying rheumatologic disease that is known to cause uveitis. We share the case of a young gentleman with ankylosing spondylitis who was being treated with secukinumab with good response to joint symptoms. He developed sudden onset uveitis which was diagnosed to be due to NTM infection based on aqueous humor polymerase chain reaction studies. He had a good clinical response to an empirical anti-mycobacterial regime with the restoration of vision. This report narrates the first case of NTM uveitis secondary to secukinumab therapy.
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LETTER TO EDITOR Top

Anemia related to linezolid-based combination regimen in drug-resistant tuberculosis p. 130
Oki Nugraha Putra, Affan Yuniar Nur Hidayatullah
DOI:10.4103/ijmy.ijmy_231_21  PMID:35295038
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