Search results for: tuberculosis (TB)

Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram

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Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

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Authors: A. G. Barua, Uttam Rajkhowa, Pranjal Moni Nath, Nur Abdul Kadir

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Mycobacterium tuberculosis (MTB) is one of the most closely-related intracellular bacterial pathogens, grouped as the M. tuberculosis complex (MTC). MTB, the primary agent of human tuberculosis (TB), can develop clinical TB in animals as 75 percent of canine mycobacterial infection is caused by close contact with an infected human being. In the present study, molecular detection of TB in dogs in three North-eastern states of India, Assam Mizoram, and Nagaland was carried out. So far, there has been a lack of systematic study in these regions, hampered by slow diagnostic methods and poor infrastructure. In an attempt to rectify this situation, molecular epidemiology was carried out for nine months to detect canine TB in a sample of 340 dogs. Isolation of DNA was done with swabs (throat/nasal), nodules of lungs and fluids from 100 suspected dogs and the molecular study were carried out with the help of conventional and real-time PCR. Post-mortem study was also carried out. Our results showed that the prevalence of clinical TB in dogs from a high-risk setting was 1 percent. However, the prevalence of immunological sensitization to M. tuberculosis antigen in dogs living in contact with sputum smeared positive TB cases was almost 50 percent. The latter setting had the maximum impact in terms of TB transmission. During the study period, a survey with a standard questionnaire was carried out in the TB hospitals to study reverse zoonosis. It was observed that an infected human being was one of the major risk factors for dogs to contract the infection. This observation was drawn by examining the probable airborne transmission from humans to their pets or strays. The present study helped to discover the nuances of TB transmission more clearly and systematically as compared to other sporadic tests to detect MTB in canine.

Keywords: Assam and Nagaland, canine TB, India, molecular detection, tuberculosis

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Authors: Gagan Dhawan

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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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Authors: Danylo Brindak, Viktor Liashko, Olexander Chepurniy

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Despite considerable experience in implementation of the best international approaches and services within response to epidemy of multi-drug resistant tuberculosis, the results of situation analysis indicate the presence of faults in this area. In 2014, Ukraine (for the first time) was included in the world’s five countries with the highest level of drug-resistant tuberculosis. The effectiveness of its treatment constitutes only 35% in the country. In this context, the increase in allocation of funds to control the epidemic of multidrug-resistant tuberculosis does not produce perceptible positive results. During 2001-2016, only the Global Fund to fight AIDS, Tuberculosis, and Malaria allocated to Ukraine more than USD 521,3 million for programs of tuberculosis and HIV/AIDS control. However, current conditions in post-Semashko system create little motivation for rational use of resources or cost control at inpatient TB facilities. There is no motivation to reduce overdue hospitalization and to target resources to priority sectors of modern tuberculosis control, including a model of care focused on the patient. In the presence of a line-item budget at medical institutions, based on the input factors as the ratios of beds and staff, there is a passive disposal of budgetary funds by health care institutions and their employees who have no motivation to improve quality and efficiency of service provision. Outpatient treatment of tuberculosis is being implemented in Ukraine since 2011 and has many risks, namely creation of parallel systems, low consistency through dependence on funding for the project, reduced the role of the family doctor, the fragmentation of financing, etc. In terms of reforming approaches to health system financing, which began in Ukraine in late 2016, NGO Infection Control in Ukraine conducted piloting of a new, motivating method of remuneration of employees in primary health care. The innovative aspect of this funding mechanism is cost according to results of treatment. The existing method of payment on the basis of the standard per inhabitant (per capita ratio) was added with motivating costs according to results of work. The effectiveness of such treatment of TB patients at the outpatient stage is 90%, while in whole on the basis of a current system the effectiveness of treatment of newly diagnosed pulmonary TB with positive swab is around 60% in the country. Even though Ukraine has 5.24 TB beds per 10 000 citizens. Implemented pilot model of ambulatory treatment will be used for the creation of costs system according to results of activities, the integration of TB and primary health and social services and their focus on achieving results, the reduction of inpatient treatment of tuberculosis.

Keywords: health care reform, multi-drug resistant tuberculosis, outpatient treatment efficiency, tuberculosis

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Authors: Shokoufeh Roudashti, Shahin Bahari, Fakhri Haghi, Habib Zeighami, Ghazal Naderi, Paniz Shirmast

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Background: Mycobacterium tuberculosis complex (MTBC) causes tuberculosis (TB) in humans and animals. Mycobacterium MTBC is one of the most important species of zoonotic pathogens that can be transmitted from cattle to humans. The disease can transmit to human by direct contact with the infected animals, drinking unpasteurized milk and consumption of uncooked meat. The presence of these opportunistic, pathogenic bacteria in bovine milk has emerged as a public-health concern, especially among individuals who consume raw milk. Tuberculosis MTBC is the predominant infectious cause of morbidity and morality worldwide, It is estimated that one third of the world population (approx. 1.8 billion persons) is infected with M. tuberculosis and each year there are 8 million new cases worldwide. The aim of this study, to detect Mycobacterium MTBC in raw milk samples using polymerase chain reaction (PCR). Materials and Methods: In the present study, 60 raw milk samples were collected from rural areas in Zanjan, Iran. After extraction of DNAs and using special primers for Is6110 gene as a marker, PCR was applied to detect the presence or non-presence of the related gene. Results: According to the findings of this study, 8 (13.5 %) out of 60 milk samples were positive for Mycobacterium spp (P < 0.1). Conclusions: The Outbreak of genus Mycobacteria spp in milk samples were determined to be relatively high in Zanjan, Iran.

Keywords: Mycobacteria spp, raw milk, PCR, Zanjan

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Authors: Aminu Bashir Mohammad, Agwu Ezera, Abdulrazaq G. Habib, Garba Iliyasu

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Background: Drug resistance tuberculosis (DR-TB) continues to be a challenge in developing countries with poor resources. Routine screening for primary DR-TB before commencing treatment is not done in public hospitals in Nigeria, even with the large body of evidence that shows a high prevalence of primary DR-TB. Data on drug resistance and its genetic determinant among follow up TB patients is lacking in Nigeria. Hence the aim of this study was to determine the prevalence and genetic determinant of drug resistance among follow up TB patients in a tertiary hospital in Nigeria. Methods: This was a cross-sectional laboratory-based study conducted on 384 sputum samples collected from consented follow-up tuberculosis patients. Standard microbiology methods (Zeil-Nielsen staining and microscopy) and PCR (Line Probe Assay)] were used to analyze the samples collected. Person’s Chi-square was used to analyze the data generated. Results: Out of three hundred and eighty-four (384) sputum samples analyzed for mycobacterium tuberculosis (MTB) and DR-TB twenty-five 25 (6.5%) were found to be AFB positive. These samples were subjected to PCR (Line Probe Assay) out of which 18(72%) tested positive for DR-TB. Mutations conferring resistance to rifampicin (rpo B) and isoniazid (katG, and or inhA) were detected in 12/18(66.7%) and 6/18(33.3%), respectively. Transmission dynamic of DR-TB was not significantly (p>0.05) dependent on demographic characteristics. Conclusion: There is a need to strengthened the laboratory capacity for diagnosis of TB and drug resistance testing and make these services available, affordable, and accessible to the patients who need them.

Keywords: drug resistance tuberculosis, genetic determinant, intensive phase, Nigeria

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Authors: Oktira Roka Aji, Maelita R. Moeis, Ihsanawati, Ernawati A. Giri-Rachman

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Globally, tuberculosis (TB) remains a leading cause of death. The emergence of multidrug-resistant strains and extensively drug-resistant strains have become a major public concern. One of the potential candidates for drug target is the cytoplasmic domain of PhoR Histidine Kinase, a part of the Two Component System (TCS) PhoR-PhoP in Mycobacterium tuberculosis (Mtb). TCS PhoR-PhoP relay extracellular signal to control the expression of 114 virulent associated genes in Mtb. The 3D structure of PhoR cytoplasmic domain is needed to screen novel drugs using structure based drug discovery. The PhoR cytoplasmic domain from Mtb H37Rv was overexpressed in E. coli BL21(DE3), then purified using IMAC Ni-NTA Agarose his-tag affinity column and DEAE-ion exchange column chromatography. The molecular weight of the purified protein was estimated to be 37 kDa after SDS-PAGE analysis. This sample was used for pre-crystallization screening by applying sitting drop vapor diffusion method using Natrix (HR2-116) 48 solutions crystal screen kit at 25ºC. Needle-like crystals were observed after the seventh day of incubation in test solution No.47 (0.1 M KCl, 0.01 M MgCl2.6H2O, 0.05 M Tris-Cl pH 8.5, 30% v/v PEG 4000). Further testing is required for confirming the crystal.

Keywords: tuberculosis, two component system, histidine kinase, needle-like crystals

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Authors: Alpana Meena

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Background: Tuberculosis is one of the major causes of death in south-east nations. Anti-TB–induced hepatotoxicity (AIH) is associated with a mortality of 6%–12%. The risk is increased when the drugs are combined. Reintroduction of anti-tuberculosis drugs in patients with AIH has never been studied systematically. The present study was planned to see the clinical profile of patients of AIH and the response to reintroduction of therapy. Methods: The trial was conducted in the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, on 32 patients with extra-pulmonary tuberculosis who developed AIH. Patients were randomly allocated into 3 groups. In group 1- Isoniazid (INH) and Rifampicin (RIF) were given at full dosages (weight calculated) from day 1. In group 2- RIF was given at maximum dosage from day 1 and INH at maximum dosage from day 8. In group 3- INH was given at maximum dosage from day 1 and RIF at maximum dosage from day 8. Pyrazinamide was added when above regimens were tolerated. Results: The mean age of presentation was 29.37±13.497 years. The incidence was found to be highest in patients with tubercular meningitis (41%) followed by abdominal, pericardial, disseminated, spinal, and lymph nodes. The mean latent period for development of AIH was 7.84 days ± 6.149 days and the median normalization days for LFT’s was 8.81 ± 4.22 days (3-21). In the study, 21% patients had recurrence of AIH with majority of patients having tolerated the reintroduction of drugs. Pyrazinamide was introduced after establishing isoniazid and rifampicin safety, thus emphasizing the role of gradual reintroduction of ATT to avoid the combined effects of hepatotoxicity. Conclusion: To conclude, the recurrence rate of hepatotoxicity was not statistically significant between the three groups studied (p > 0.05), and thus all 3 hepatotoxic drugs can be reintroduced safely in patients developing AIH.

Keywords: anti-tubercular therapy induced hepatotoxicity, extra-pulmonary tuberculosis, reintroduction regimens, risk factors

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Authors: Muhammad Younas, Zimal Naveed

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Introduction : TB is caused by the bacillus Mycobacterium tuberculosis, which is spread when people who are sick with TB expel bacteria into the air (e.g. by coughing). The 30 high TB burden countries accounted for 87% of all estimated incident cases worldwide, and eight of these countries accounted for more than two thirds of the global total: India (27%), Indonesia (10%), China (7.1%), the Philippines (7.0%), Pakistan (5.7%), Nigeria (4.5%), Bangladesh (3.6%) and the Democratic Republic of the Congo (3.0%). Objective : To analyze prevalence of tuberculosis among the people who presented at THQ hospital Bhalwal between April 2024 to June 2024. Method : Total of 9200 patients presented in the OPD of THQ hospital Bhalwal were included in the study. These presumed cases underwent diagnostic testing by sputum for AFB, Gene expert and chest x rays. The data was then classified based Pulmonary and Extra-pulmonary TB disease and further classified on the basis of bacteriology positive and clinically diagnosed TB. The registered TB cases were then classified in 8 age groups in years and according to the gender. All the registered TB cases were then tested for HIV to observe the relation between Tuberculosis and HIV. Results : The total of 9200 patients presented to OPD during the period of 3 months between April 2024 to June 2024. Total registered cases of Tuberculosis were 161 (comprising 153 new cases and 8 cases after treatment failure). Out of the new cases 83 were males and 70 female cases were identified. The majority of males that were identified lies between age 55-64 and 65 and above while the majority of females that were diagnosed lies in the age group of 5-14 and 15-24. All the registered cases were then tested for HIV but none of them were found to be positive. Conclusion : According to World Health Organisation Global Tuberculosis Report, the incidence of Tubeculosis per 100000 people was 258, equivalent to 0.258 %. However, the study reveals an exceptionally high frequency of TB cases. The prevalence of Tuberculosis per 100000 people was found to be 1750 which is equivalent to 1.75 %. The study revealed that larger proportion of the population is currently affected by TB compared to the global average incidence reported by the WHO. The findings of the study indicates that the prevalence of tuberculosis (TB) among females is most common in the younger population, specifically between the ages of 5 to 24, and particularly within the peak fertility age group of 15 to 24 years. The health of women in their peak fertility years is crucial for maternal and child health outcomes. This highlights the need for targeted public health interventions in this area to manage and reduce the burden of TB.

Keywords: AGE, AFB, female, male

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Authors: Haji Ali Haji, Hussein Suleman, Ulrike Rivett

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This paper presents the design, development and evaluation of an application prototype developed to support tuberculosis (TB) patients’ treatment adherence. The system makes use of graphics and voice reminders as opposed to text messaging to encourage patients to follow their medication routine. To evaluate the effect of the prototype applications, participants were given mobile phones on which the reminder system was installed. Thirty-eight people, including TB health workers and patients from Zanzibar, Tanzania, participated in the evaluation exercises. The results indicate that the participants found the mobile graphic-based application is useful to support TB treatment. All participants understood and interpreted the intended meaning of every image correctly. The study findings revealed that the use of a mobile visual-based application may have potential benefit to support TB patients (both literate and illiterate) in their treatment processes.

Keywords: ICT4D, mobile technology, tuberculosis, visual-based reminder

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

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Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

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Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

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Authors: Prasanthi Malapati, R. Reshma, Vijay Soni, Perumal Yogeeswari, Dharmarajan Sriram

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In the present study, we attempted to develop Mycobacterium tuberculosis (Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets which are majorly involved in cell wall biosynthesis of mycobacteria. For this purpose, glutamate racemase (coded by MurI gene) was selected. This enzyme racemize L-glutamate to D-glutamate required for the construction of peptidoglycan in the bacterial cell wall synthesis process. Furthermore this enzyme is neither expressed nor its product, D-glutamate is normally found in mammals, and hence designing inhibitors against this enzyme will not affect the host system as well act as potential antitubercular drugs. A library of BITS in house compounds were screened against Mtb MurI enzyme. Based on docking score, interactions and synthetic feasibility one hit lead was identified. Further optimization of lead was attempted and its derivatives were synthesized. Forty eight derivatives of 2-phenylbenzo[d]oxazole and 2-phenylbenzo[d]thiazole were synthesized and evaluated for Mtb MurI inhibition study, in vitro activities against Mtb, cytotoxicity against RAW 264.7 cell line. Chemical derivatization of the lead resulted in compounds NR-1213 AND NR-1124 as the potent M. tuberculosis glutamate racemase inhibitors with IC50 of 4-5µM which are remarkable and were found to be non-cytotoxic. Molecular dynamics, dormant models and cardiotoxicity studies of the most active molecules are in process.

Keywords: cell wall biosynthesis, dormancy, glutamate racemase, tuberculosis

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Authors: Muhammad Imran Hussain, Ramisha Ibtisam, Tayyaba Fatima, Huba Khalid, Ayesha Aziz, Khansa, Adan Sitara, Anam Shahzad, Aymen Jabeen

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Vitamin D supports the immune system fight TB by inhibiting Interferon-gamma (IFN-γ) and lowering host inflammation. The purpose of the research was to see if giving the vitamin D supplements to TB patients affected their prognosis. A randomized placebo control study of 200 TB patients was performed among which 106 received 400,000 IU of injectable vitamin D3 and 94 received placebo for 2 doses. Assessment was carried out at the end of every month for 3 months. IFN-γ responses to whole blood stimulation generated by the Mycobacterium tuberculosis sonicate (MTBs) antigen and early secreted and T cell activated 6 kDa (ESAT6) were assessed at 0 and 12 weeks. The statistical analysis used descriptive statistics (mean and standard deviation), Friedman's test and Fisher's test. The vitamin D group gained significantly more weight (+3.90 pounds) and had less persistent lung disease on imaging (1.33 zones vs. 1.84 zones). They also had a 50% decrease in cavity size. Additionally, patients with low baseline serum concentrations of 25-(OH)D had a significant increase in MTB-induced IFN-γ production after taking vitamin D supplements. Vitamin D administration in large amounts can hasten the recovery of TB patients. The findings point is a therapeutically useful activity of Vitamin D's in the management for tuberculosis.

Keywords: tuberculosis, vitamin D, interferon gamma, protein, infection

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Authors: Domingos Vita, Patrick Brady

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Background: There is a tuberculosis (TB) epidemic in Angola that has been getting worse for more than a decade despite the active implementation of the DOTS strategy. The aim of this study was to directly interrogate healthcare workers involved in TB control on what they consider to be the drivers of the TB epidemic in Angola. Methods: Twenty four in-depth qualitative interviews were conducted with medical staff working in this field in the provinces of Luanda and Benguela. Results: The healthcare professionals see the migrant working poor as a particular problem for the control of TB. These migrants are constructed as ‘Rural People’ and are seen as non-compliant and late-presenting. This is a stigmatized and marginal group contending with the additional stigma associated with TB infection. The healthcare professionals interviewed also see the interruption of treatment and self medication generally as a better explanation for the TB epidemic than urbanization or lack of medication. Conclusions: The local narrative is in contrast to previous explanations used elsewhere in the developing world. To be effective policy must recognize the local issues of the migrant workforce, interruption of treatment and the stigma associated with TB in Angola.

Keywords: Africa, Angola, migrants, qualitative, research, tuberculosis

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Authors: M. Nosik, I. Rymanova, N. Adamovich, S. Sevostyanihin, K. Ryzhov, Y. Kuimova, A. Kravtchenko, N. Sergeeva, A. Sobkin

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HIV and Tuberculosis (TB) infections each speed the other's progress. HIV-infection increases the risk of TB disease. At the same time, TB infection is associated with clinical progression of HIV-infection. HIV+TB co-infected patients are also at higher risk of acquiring new opportunistic infections. An important feature of disease progression and clinical outcome is the innate and acquired immune responses. HIV and TB, however, have a spectrum of dysfunctions of the immune response. As cytokines play a crucial role in the immunopathology of both infections, it is important to study immune interactions in patients with dual infection HIV+TB. Plasma levels of proinflammatory cytokines IL-2, IFN-γ and immunoregulating cytokines IL-4, IL-10 were evaluated in 75 patients with dual infection HIV+TB, 58 patients with HIV monoinfection and 50 patients with TB monoinfection who were previously naïve for HAART. The decreased levels of IL-2, IFN-γ, IL-4 and IL-10 were observed in patients with dual infection HIV+TB in comparison with patients who had only HIV or TB which means the profound suppression of Th1 and Th2 cytokine secretion. Thus, those cytokines could possibly serve as immunological markers of progression of HIV-infection in patients with TB.

Keywords: HIV, tuberculosis (TB), HIV associated with TB, Th1/ Th2 cytokine expression

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Authors: Muhammad Shahbaz Akhtar

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Background; Tuberculosis remains a significant public health challenge in Pakistan, with high incidence and prevalence rates, particularly among vulnerable populations. Addressing the TB burden requires comprehensive efforts to improve healthcare infrastructure, increase access to quality diagnosis and treatment services, raise public awareness, and address socioeconomic determinants of health. Objective; To assess the knowledge and practices of healthcare workers and patients regarding prevention of tuberculosis at a tertiary care hospital of Southern Punjab.Material and methods; Data will be collected from 135 healthcare workers and 135 TB patients visiting Nishtar Hospital, Multan in this descriptive cross – sectional study using non – probability consecutive sampling technique. Proper approval will be taken from Hospital authorities to conduct this study. Study participants will be recruited after taking informed written consent, describing them objectives of this study. The study participants will be ensured of their confidentiality of the data and interviewed to assess their knowledge and practices regarding prevention of tuberculosis. Data Analysis Procedure; Data will be entered and analyzed by using SPSS version 25 to calculated mean and standard deviation for the numerical data such as age, duration of disease and duration of experience. Frequencies and percentages will be calculated for gender, age groups, level of knowledge, qualification, designation and practices. Impact of confounders like gender, age groups, duration of experience, disease duration, years of experience and designation will be assessed by stratification. Post stratification chi – square test will be applied at 0.05 level of significance at 95 % CI.

Keywords: tuberculosis, data analysis, HIV/AIDS, preventable

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Authors: R. K. Yadav, S. Baral, H. R. Paudel, R. Basnet

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The Public-Private Mix (PPM) approach is a strategic initiative that involves engaging all private and public healthcare providers in the fight against tuberculosis using international healthcare standards. For tuberculosis control in Nepal, the PPM approach could be a milestone. This study aimed to explore the barriers to a public-private mix approach in the management of tuberculosis cases in Nepal. A total of 20 respondents participated in the study. Barriers to PPM were identified in the following three themes: 1) Obstacles related to TB case detection, 2) Obstacles related to patients, and 3) Obstacles related to the healthcare system. PPM implementation was challenged by following subthemes that included staff turnover, low private sector participation in workshops, a lack of training, poor recording and reporting, insufficient joint monitoring and supervision, poor financial benefit, lack of coordination and collaboration, and non-supportive TB-related policies and strategies. The study concludes that numerous barriers exist in the way of effective implementation of the PPM approach, including TB cases detection barriers such as knowledge of TB diagnosis and treatment, HW attitude, workload, patient-related barriers such as knowledge of TB, self-medication practice, stigma and discrimination, financial status, and health system-related barriers such as staff turnover and poor engagement of the private sector in workshops, training, recording, and re-evaluation. Government stakeholders must work together with private sector stakeholders to perform joint monitoring and supervision. Private practitioners should receive training and orientation, and presumptive TB patients should be given adequate time and counseling as well as motivation to visit a government health facility.

Keywords: barrier, tuberculosis, case finding, PPM, nepal

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Authors: Abu Salim Mustafa

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Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.

Keywords: mycobacterium tuberculosis, PPE68, peptides, vaccine

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Authors: Begna Tulu, Gobena Ameni

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Understanding the types of Mycobacterium bovis (M. bovis) strains circulating in a country and exploring its zoonotic potential has significant contribution in the effort to design control strategies. The main aim of this study was to review and compile the results of studies conducted on M. bovis genotyping and its zoonotic potential of M. bovis in Ethiopia. A systematic search and review of articles published on M. bovis strains in Ethiopia were made. PubMed and Google Scholar databases were considered for the search while the keywords used were 'Mycobacteria,' 'Mycobacterium bovis,' 'Bovine Tuberculosis' and 'Ethiopia.' Fourteen studies were considered in this review and a total of 31 distinct strains of M. bovis (N=211) were obtained; the most dominant strains were SB0133 (N=62, 29.4%), SB1176 (N=61, 28.9%), and followed by SB0134 and SB1476 each (N=18, 8.5%). The clustering rate of M. bovis strains was found to be 42.0%. On the other hand, 6 strains of M. bovis were reported from human namely; SB0665 (N=4), SB0303 (N=2), SB0982 (N=2), SB0133 (N=1), SB1176 (N=1), and 1 new strain. Similarly, a total of 8 strains (N=13) of M. tuberculosis bacteria were also identified from animal subjects; namely SIT149 (N=3), SIT1 (N=2), SIT1688 (n=2), SIT262 (N=2), SIT53 (N=1), SIT59 (N=1), and one new-Ethiopian strain. The result showed that the genetic diversity of M. bovis strains reported from Ethiopia are less diversified and highly clustered. And also the result underlines that there is an ongoing active transmission of M. bovis and M. tuberculosis between human and animals in Ethiopia because a significant number strains of both type of bacteria were reported from human and animals.

Keywords: mycobacterium bovis, Mycobacterium tuberculosis, zoonotic potential, genetic diversity, Ethiopia

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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Authors: Ilham Zaidi, P. Sankara Sarma, Quazi Taufique Ahmed, V. Raman Kutty, Khalid Umer Khayyam, Gurpreet Singh, Abhishek Royal

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Introduction: Tuberculosis is a global public health emergency, but it is particularly acute in India, which has the world's highest tuberculosis burden. Due to overpopulation, lack of sanitation, malnutrition, low living standards, and poor socioeconomic status, among other factors, it is India's most common infectious disease. The long period of treatment is one of the main reasons for considering it as a public health emergency. Consequently, there is an increase in patient noncompliance, which leads to treatment failure, adverse treatment outcomes, and deaths. This could lead to the growth of anti-TB drug resistance. According to the WHO, approximately 558 thousand new cases of Multi-Drug Resistance Tuberculosis were diagnosed worldwide, with 8.5 percent developed Extensively Drug Resistance Tuberculosis. Methodology: This study is a program-based cross-sectional descriptive survey of adult tuberculosis patients enrolled in the Delhi-based Revised National Tuberculosis Program. The study setting was 27 NTEP districts of Delhi. (N=65,893) and Sample size- was 200; the sampling method which is used in the study was the systemic random sampling method. Results: Most of the demographic factors (age, gender, residence, and family type) were not significantly associated with adherence; marital status was found statistically significant with the treatment compliance. Hesitation while telling people about the disease and motivation to strictly follow drug schedule by healthcare workers were other factors where a significant association with drug adherence was observed. The study findings also suggest that provision of food, minimal financial and other moral support from family, counseling, discussion and politeness by healthcare providers might also facilitate adherence. Discussion and Conclusions: For TB treatment, adherence, age, sex, socioeconomic status, types of accommodations, malnutrition, and personal hygiene should all be considered; similar results were observed in previous studies. In the care of TB patients, DOTS services, health workers, and family support play a significant role. According to the country's National Strategic Plan, the Indian government has set a goal of eliminating tuberculosis by 2025 and patients' compliance with TB care and treatment adherence is very crucial to achieve this aim. A cohort study will be able to give a better understanding of factors associated with adherence since this study may have missed some defaulters who were absconding and could not be reached. Important Terms: RNTCP, NTEP, DOTS, DS-TB, DR-TB, RR-TB, MDR-TB, XDR-TB, Treatment failure, Treatment relapse, Treatment adherence.

Keywords: treatment adherence, treatment relapse, treatment failure, drug resistance tuberculosis

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Authors: Rosalina Penaloza, Joanna Navarro, Pauline Jolly, Anna Junkins, Carlos Seas, Larissa Otero

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Background: Tuberculosis (TB) case detection in Peru relies on passive case finding. This strategy relies on the assumption that the community is aware that a persistent cough is a possible symptom of TB and that formal health care needs to be sought. Despite its importance, health knowledge specific to TB is underexplored in Peru. This study aimed to assess health literacy and level of TB knowledge among outpatients attending a referral hospital in Lima, Peru. The goal was to ascertain knowledge gaps in key areas relating to TB, to identify and prioritize subgroups for intervention, and to provide insight for policy and community interventions considering health literacy. Methods: An observational cross-sectional study was conducted using a survey to measure sociodemographic factors, tuberculosis knowledge, and health literacy. Bivariate and Multivariate logistic regression was performed to study the associations between variables and to account for potential confounders. The study was conducted at Hospital Cayetano Heredia in Lima, Peru from June – August 2017. Results: 272 participants were included in the analysis. 57.7% knew someone who had had TB before, 9% had had TB in the past. Two weeks a cough was correctly identified as a symptom that could be TB by 69.1%. High TB knowledge was found among 149 (54.8%) participants. High health literacy was found among 193 (71.0%) participants. Health literacy and TB knowledge were not significantly associated (OR 0.9 (95%CI 0.5-1.5)). After controlling for sex, age, district, education, health insurance, frequency of hospital visits and previous TB diagnosis: High TB knowledge was associated with knowing someone with TB (aOR 2.7 (95%CI 1.6-4.7)) and being a public transport driver, (aOR 0.2 (95%CI 0.05-0.9)). Not being poor was the single factor associated with high health literacy (aOR 3.8 (95%CI 1.6-8.9)). Conclusions: TB knowledge was fair, though 30% did not know the most important symptom of TB. Tailoring educational strategies to risk groups may enhance passive case detection especially amongst transport workers in Lima, Peru.

Keywords: health literacy, Peru, tuberculosis, tuberculosis knowledge

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Shima Mahmoudi, Babak Pourakbari, Setareh Mamishi, Mostafa Teymuri, Majid Marjani

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Although cytokine analysis has greatly contributed to the understanding of tuberculosis (TB) pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce. Since PE/PPE proteins are known to induce strong humoral and cellular immune responses, the aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. All the patients with active TB and LTBI had positive QuantiFERON-TB Gold in Tube test. The level of IL-2 following stimulation with recombinant PE35 and PPE68 were significantly higher in LTBI group than in patients with active TB infection or control group. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 (95%CI: 0.72-0.97) and 0.75 (95%CI: 0.63-0.89), respectively. Applying the 12.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 78%, PPV of 78% and NPV of 100%. In addition, a sensitivity of 81%, specificity of 70%, PPV of 67% and 87% of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. In conclusion, peptides of the antigen PE35 and PPE68, absent from commonly used BCG strains, stimulated strong IL-2- positive T cell responses in patients with LTBI. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and Active TB infection.

Keywords: IL-2, PE35, PPE68, tuberculosis

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Authors: Seyed Davar Siadat, Samira Tarashi, Abolfazl Fateh, Arfa Moshiri

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Background: The global health issue of tuberculosis (TB) still affects patients in every country. TB control may not be as effective as it should be, especially when resistant strains are involved. In this regard, mycobacterial MTases play a major role in tuberculosis, but the mechanisms underlying their function have yet to be fully deciphered. Methods: Five resistant isolates of M.tb were accumulated. As a reference strain, M.tb H37Rv (ATCC 27249) was used. For this analysis, seven putative mycobacterial MTase genes (Rv0645c, Rv1694, Rv2966c, Rv3919c, Rv2756c, Rv1988, and Rv3263), as well as Rv1392 as SAM synthase, were selected. Comparing mutations and expression levels of MTases in different strains was accomplished by PCR-sequencing and qRT-PCR. The relative expression levels of these genes were calculated using the 2 -ΔΔCt method. Results: The Rv3919c gene (T to G in codon 341) and Rv1392 gene (G to A in codon 97) were the only mutations found in the INHR strain. In all sensitive and resistant isolates, Rv0645c, Rv3263, Rv2756c, and Rv2966c were overexpressed. However, the expression of Rv1988 and Rv3919c decreased in the sensitive strains, whereas the expression of Rv1694 increased. There was also a decreased expression of Rv1392 in the INHR isolate. Conclusion: The presence of mycobacterial MTases as well as resistance to antibiotics were found to be correlated in M.tb strains. Undoubtedly, there are some MTases that are associated with the virulence process. It is necessary to conduct additional studies to fully explore the impact of mycobacterial MTases within specific strains of M.tb to develop novel diagnostic and treatment strategies.

Keywords: mycobacterium tuberculosis, drug resistance, methyltransferases, s-adenosylmethionine

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Authors: Yadav R. K., Baral S.

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Introduction: Nepal is one of the world’s least developed countries and has a high incidence of tuberculosis (TB). The TB prevalence survey in 2019 showed 69,000 Nepalese is developing TB and 4,000 die every year. Given its disproportionate impact on the impoverished segments of society, TB often thrusts patients into extreme poverty or exacerbates their existing economic struggles. Consequently, not only the patients but also their families suffer from the loss of livelihood. This study aims to assess the support of nutritional allowance on treatment compliance among retreatment tuberculosis patients in Nepal. This is a secondary analysis of data from HMIS (Health Management Information System) to investigate treatment compliance among tuberculosis patients and its association with nutritional allowance. The study population consisted of all individuals (N=2972) who had received services from July 16, 2021, to December 14, 2022. The SPSS 21version was used to conduct descriptive and bivariate analysis. Out of the total TB patients (n=2972), a third-fourth (65.9%) of TB patients were male. More than one-tenth (12.3%) of respondents received a nutrition support allowance. The TB treatment compliance rate was more (89.91%) in the nutrition support allowance group compared to the non-nutritional support group (87.98%). TB patients who received the nutritional support allowance were nearly twice as likely to have a higher TB treatment compliance rate compared to those who did not receive the nutritional support allowance. Providing nutritional allowance support to tuberculosis (TB) patients can play a significant role in improving treatment compliance and outcomes. Age and the type of TB are important factors that have shown statistical significance in relation to treatment compliance. Therefore, it is recommended to provide nutritional allowance support to both new and retreatment TB patients. To enhance treatment compliance among TB patients, it is beneficial to provide timely nutrition allowances and arrange home visits by TB focal persons.

Keywords: nutrition, support, treatment compliance, TB, Nepal

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Authors: Atefeh Abedini, Pegah Soltani, Arda Kiani

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Background: Sarcoidosis and Tuberculosis are both considered granulomatous chronic diseases with some similar pulmonary and extra-pulmonary manifestations. It is hypothesized that given these morphological similarities, the genome of mycobacterium could have an impact on the development of Sarcoidosis. Identifying the potential correlation of these diseases may assist in the management of sarcoidosis. Herein, we aimed to inspect the lymph node biopsy of sarcoidosis patients for the existence of the HSP-65 mycobacterium DNA sequence. Methods: This cross-sectional survey was conducted on 1188 Sarcoidosis patients without active/latent tuberculosis infection who were diagnosed in Masih Daneshvari Hospital in Tehran, Iran, from January 2020 to January 2022. Trans-bronchial needle aspiration (TBNA) was performed due to bilateral hilar lymphadenopathy to take a specimen. Results: The under-evaluated patients were mainly women (N=815 (68.6%)), none-smoker (N=1016 (85.5%)), and middle-aged (50.1 (SD=4.22)) with average angiotensin-converting enzyme (ACE) index of 75.6 (SD=6.42). Dyslipidemias (n=314 (26.4%), Hypertension (n=295 (24.8%)), Diabetes mellitus (n=131 (11.0%)), and chronic heart diseases (n=97 (8.2%)) had the highest prevalence between comorbidities. Skin lesions (n= 655 (55.1%)), ophthalmic (n=341 (28.7%)), and cardiac involvement (n=229 (19.3%)) were obtained as the most common extra-pulmonary characteristics of the patients. Amongst 1188 enrolled patients who were not afflicted with Mycobacterium tuberculosis based on smear/culture essay, clinical symptoms, and Chest x-ray screening, 121 (10.2%) cases had detectable amplified DNA for Mycobacterium Tuberculosis extracted from mediastinal lung lymph nodes. Conclusion: In this survey, the mycobacterium genome was detected in almost 1 per 10 case biopsies of sarcoidosis. The remarkable number of cases (n=1188) evaluated in this study was the strength of this study which supported the hypothesis regarding sarcoidosis and mycobacterium genome correlation. Further investigation, such as case-control surveys, is required to better clarify this association.

Keywords: mycobacterium tuberculosis, sarcoidosis, genome, DNA, trans-bronchial needle aspiration

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Authors: Ghoul Rachid Brahim

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Introduction: Tuberculous spondylodiscitis is an infection of the spine by Mycobacterium tuberculosis. Tuberculous spondylodiscitis still remains a topical disease in developing countries and continues to pose a public health problem in endemic countries. Materials and methods: Clinical case: This is a 12-year-old child followed in pediatrics for weight loss and progressively worsening low back pain. The neurological examination found an irritative pyramidal syndrome in both lower limbs with a severe lumbar spinal syndrome. The radiological assessment: (Rx of the spine supplemented by CT and MRI) shows L1L2 spondylodiscitis. Treatment: The child is put on anti-tuberculosis treatment, and the spine is restrained with a corset. Control MRI shows a worsening of the dorsal kyphosis with a backward movement of the posterior wall and spinal cord compression. The child is operated on via the posterior approach (the operative procedure consists of an L1 laminectomy and D11 L3 osteosynthesis). Results: Spinal cord décompression and stabilization of the spine. Conclusion: Tuberculous spondylodiscitis in children remains a rare, aggressive, and progressive condition. The prognosis depends on the diagnosis's precocity and the therapeutic management quality.

Keywords: tuberculous spondylodiscitis, mycobacterium tuberculosis, laminectomy, MRI

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