Search results for: tuberculosis infection

Authors: Saima Suleman, Kalsoom Sughra, Naeem Mahmood Ashraf

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Mycobacterium tuberculosis is a communicable chronic illness. This disease is being highly focused by researchers as it is present approximately in one third of world population either in active or latent form. The genetic makeup of a person plays an important part in producing immunity against disease. And one important factor association is single nucleotide polymorphism of relevant gene. In this study, we have studied association between single nucleotide polymorphism of CD-209 gene (encode DC-SIGN receptor) and patients of tuberculosis. Dry lab (in silico) and wet lab (RFLP) analysis have been carried out. GWAS catalogue and GEO database have been searched to find out previous association data. No association study has been found related to CD-209 nsSNPs but role of CD-209 in pulmonary tuberculosis have been addressed in GEO database.Therefore, CD-209 has been selected for this study. Different databases like ENSEMBLE and 1000 Genome Project has been used to retrieve SNP data in form of VCF file which is further submitted to different software to sort SNPs into benign and deleterious. Selected SNPs are further annotated by using 3-D modeling techniques using I-TASSER online software. Furthermore, selected nsSNPs were checked in Gujrat and Faisalabad population through RFLP analysis. In this study population two SNPs are found to be associated with tuberculosis while one nsSNP is not found to be associated with the disease.

Keywords: association, CD209, DC-SIGN, tuberculosis

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Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

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New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

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Authors: Naima Nur, Safa Islam, Saeema Islam, Md. Faridul Alam

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Background: The worldwide increase in pediatric presumptive tuberculosis (TB) is the most life-threatening challenge in effectively controlling TB. The objective of this study was to determine the proportion of presumptive TB and the factors associated with it. Methods: A cross-sectional study was conducted between March and November 2013 at ICDDR-Bangladesh. Two hundred twelve pulmonary and extra-pulmonary specimens were collected from 84 suspected pediatric patients diagnosed with TB based on their clinical symptoms/radiological findings. Presumptive TB and confirmed TB were considered presumptive TB and non-presumptive TB and were isolated by smear-microscopy, culture, and GeneXpert. Logistic regression was used to analyze associations between outcome and predictor variables. Results: The proportion of presumptive TB was 85.7%, and 14.3% of non-presumptive TB. In presumptive TB, vaccine scars, family TB history, and school-going children were 16.6%, 33.3%, and 56.9%, respectively. In contrast, vaccine scars and family TB history were 8.3%, and school-going children were 58.3% in non-presumptive TB. Significant factors did not appear in the logistic regression analysis. Conclusion: Despite the high proportion of presumptive TB, there was no statistically significant between presumptive TB and non-presumptive TB.

Keywords: presumptive tuberculosis, confirmed tuberculosis, patient's characteristics, diagnosis

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Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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Authors: Udaykumar R., M. S. Ganachari

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In order to engage community pharmacies in Tuberculosis care, a survey has been conducted in Belgaum city, Karnataka state, India. After the survey divided into two groups one is control group and another one is intervention group. One is dispensing of anti-tuberculosis drugs, and another one is non-availability of anti-tuberculosis drugs. Those community pharmacists who are voluntarily interesting for becoming DOTS (Directly observed treatment short course) provider and RNTCP (Revised national tuberculosis control programme) objectives. Structured training is conducted for community pharmacist who are dispensing anti-tuberculosis drugs. The training module includes record maintaining, reporting to the RNTCP, Medication adherence etc. In case of non-availability of anti-tuberculosis drugs, the district RNTCP has been given training for community pharmacist by providing free of drugs to the community pharmacies. So, community pharmacies can dispense anti-tuberculosis drugs to the patients. The target of this study is Private community pharmacies. A simple random sampling method is used and 550 private community pharmacy shops has been involved in Belgaum city of Karnataka state, India. Significance of the Study: This study mainly focused on training of DOTS (Directly observed treatment short course) to the private community pharmacist. Indian Govt. Considers Private Providers as Assets for TB Control and Care to Achieve National Strategic Plan for TB Elimination 2017-2025. The Govt. has not fully tapped the Potential of Private Pharmacies to Fight TB. Providing DOTS as per patient’s convenience through community DOT Providers with periodic monitoring may reduce the treatment Default. We explore RNTCP objectives interventions that can have directly managed by private community pharmacy shop. Objectives: Survey of anti-tuberculosis drugs in Community pharmacy shop in Belgaum city. Interested community pharmacist who are willing to become DOTS (Directly observed treatment short course) Provider. Major Findings:Most of the community pharmacist are dispensing anti-tuberculosis drugs without having knowledge of DOTS therapy and RNTCP objectives. No community pharmacist is aware of RNTCP and Tuberculosis burden in India. Most of the Pharmacist agreed to come for RNTCP Training module for the community pharmacist. Some of the community pharmacist not dispensing anti-tuberculosis drugs and they agreed to become official DOTS provider. Concluding Statement: Awareness of role of community pharmacist on tuberculosis control and care has been neglected. More than 50% of tuberculosis patients seeking treatments from privatesector. In this study finds the major gap between government and private sector on tuberculosis treatment.

Keywords: community pharmacist, directly observed treatment short course(DOTS), revised national tuberculosis control programme (RNTCP), private pharmacies, anti-tuberculosis drugs

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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: Upvan Chobera

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India bears the highest burden of tuberculosis globally, facing a significant incidence rate. To combat this public health challenge, the Ministry of Health and Family Welfare in India has launched an ambitious national strategic plan with the aim of achieving END TB targets by 2025. Addressing tuberculosis requires a comprehensive, multi-sectoral approach that encompasses factors such as nutritional support, living and working conditions, and improved access to diagnostics and treatment services. This study delves into the burden of tuberculosis in India, examining the government's strategic plan to combat the disease. Additionally, it explores the role of Ni-Kshay Mitra (community support) in this fight, encompassing various entities such as cooperative societies, corporations, elected representatives, individuals, institutions, non-government organizations, and political parties or individual donors. These efforts aim to enhance the response against tuberculosis, complementing the government's initiatives and catering to district-specific requirements, all coordinated with the district administration. It is important to note that the support provided under the Ni-Kshay Mitra initiative is supplementary to the free services offered by the National TB Elimination Program (NTEP) available to all patients.

Keywords: end TB targets, Ni-kshay Mitra, NTEP, tuberculosis burden in India

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Authors: Mmamapudi Kubjane, Natacha Berkowitz, Rene Goliath, Naomi S. Levitt, Robert J. Wilkinson, Tolu Oni

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Background: South Africa remains a high tuberculosis (TB) burden country globally and the burden of diabetes – a TB risk factor is growing rapidly. As an infectious disease, TB also induces transient hyperglycaemia. Therefore, screening for diabetes in newly diagnosed tuberculosis patients may result in misclassification of transient hyperglycaemia as diabetes. Objective: The objective of this study was to determine and compare the prevalence of hyperglycaemia (diabetes and impaired glucose regulation (IGR)) in TB patients and to assess the cross-sectional association between TB and hyperglycaemia at enrolment and after three months of follow-up. Methods: Consecutive adult TB and non-TB participants presenting at a TB clinic in Cape Town were enrolled in this cross-sectional study and follow-up between July 2013 and August 2015. Diabetes was defined as self-reported diabetes, fasting plasma glucose (FPG) ≥ 7.0 mmol·L⁻¹ or glycated haemoglobin (HbA1c) ≥ 6.5%. IGR was defined as FPG 5.5– < 7.0 mmol·L⁻¹ or HbA1c 5.7– < 6.5%. TB patients initiated treatment. After three months, all participants were followed up and screened for diabetes again. The association between TB and hyperglycaemia was assessed using logistic regression adjusting for potential confounders including sex, age, income, hypertension, waist circumference, previous prisoner, marital status, work status, HIV status. Results: Diabetes screening was performed in 852 participants (414 TB and 438 non-TB) at enrolment and in 639 (304 TB and 335 non-TB) at three-month follow-up. The prevalence of HIV-1 infection was 69.6% (95% confidence interval (CI), 64.9–73.8 %) among TB patients, and 58.2% (95% CI, 53.5–62.8 %) among the non-TB participants. Glycaemic levels were much higher in TB patients than in the non-TB participants but decreased over time. Among TB patients, the prevalence of IGR was 65.2% (95% CI 60.1 - 69.9) at enrollment and 21.5% (95% CI 17.2-26.5) at follow-up; and was 50% (45.1 - 54.94) and 32% (95% CI 27.9 - 38.0) respectively, among non-TB participants. The prevalence of diabetes in TB patients was 12.5% (95% CI 9.69 – 16.12%) at enrolment and 9.2% (95% CI, 6.43–13.03%) at follow-up; and was 10.04% (95% CI, 7.55–13.24%) and 8.06% (95% CI, 5.58–11.51) respectively, among non-TB participants. The association between TB and IGT was significant at enrolment (adjusted odds ratio (OR) 2.26 (95% CI, 1.55-3.31) but disappeared at follow-up 0.84 (0.53 - 1.36). However, the TB-diabetes association remained positive and significant both at enrolment (2.41 (95% CI, 1.3-4.34)) and follow-up (OR 3.31 (95% CI, 1.5 - 7.25)). Conclusion: Transient hyperglycaemia exists during tuberculosis. This has implications on diabetes screening in TB patients and suggests a need for diabetes confirmation tests during or after TB treatment. Nonetheless, the association between TB and diabetes noted at enrolment persists at 3 months highlighting the importance of diabetes control and prevention for TB control. Further research is required to investigate the impact of hyperglycaemia (transient or otherwise) on TB outcomes to ascertain the clinical significance of hyperglycemia at enrolment.

Keywords: diabetes, impaired glucose regulation, transient hyperglycaemia, tuberculosis

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Authors: Ibrahim Alshunaibir

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Infection with Helicobacter pylori is common worldwide but few studies focus on the prevalence and spread of the infection in Saudi Arabia. This study was undertaken to observe the epidemiology of Helicobacter pylori infection in patients suffering from gastrointestinal sign and symptoms in one of the largest hospitals in the capital of Saudi Arabia, Riyadh. Methods: Enzyme-linked immunosorbent assay (ELISA) was undertaken for this study with nearly 6000 samples collected and examined for patients suffering from (dyspeptic) symptoms ranging in their age from 5 to 75 years. Results: The prevalence of helicobacter infection was 67% increasing with age. Female shows higher percentage of H. pylori infection than male. Conclusions: The percentage rate was higher in female than male. This study shows a high percentage of helicobacter infection in Saudi Arabia.

Keywords: Helicobacter pylori, percentage, dyspeptic, Saudi Arabia

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Authors: Yulistiani Yulistiani, Zamrotul Izzah, Lintang Bismantara, Wenny Putri Nilamsari, Arif Bachtiar, Budi Suprapti

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Interferon-gamma (IFN-γ) and interleukin-6 (IL-6) are pro-inflammatory cytokines, which have the protective immune response against Tuberculosis (TB). Indeed, pro-inflammatory cytokines Mycobacterium tuberculosis antigen-specific CD4+ and CD8+ T cells and NK cells increase the level of production of IFN-γ, a cytokine critical for augmenting the microbicidal activity of phagocytes. On the other hand, M. tuberculosis reduces the effects of IFN-γ by inhibiting the transcription of IFN-γ- responsive genes and by inducing the secretion of IL-6, which inhibits IFN-γ signaling. Probiotics Lactobacillus sp. and Bifidobacterium sp. were known to increase IFN-γ production in vivo, while vitamin B1, B6, and B12 worked on macrophages and releasing cytokines. Therefore, the present study was to evaluate the effect of probiotics and vitamin B supplement on changes of plasma cytokine levels in active pulmonary TB. From October to November 2016, twelve M. tuberculosis-infected patients starting anti-TB drugs were recruited, then divided into two groups. Seven patients were given a combination of probiotics and vitamin B, while five patients were in the control group. Plasma IFN-γ and IL-6 levels were measured by the ELISA kit before and a month after treatment. IFN-γ levels raised in four patients receiving the supplement (P = 0.743), while IL-6 increased in three patients in this group until day 30 of treatment (P = 0.298). Taken together, these results show the promising effect of probiotics and vitamin B on stimulation of IFN-γ and IL-6 production during intensive therapy of TB.

Keywords: interferon-gamma, interleukin-6, probiotic, tuberculosis

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Authors: Yung-Feng Yen, Yun-Ju Lai

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Background: Animal studies have shown that alcohol exposure may cause immunosuppression and increase the susceptibility to tuberculosis (TB) infection. However, the temporality of alcohol consumption with subsequent TB development remains unclear. This nationwide population-based cohort study aimed to investigate the impact of alcohol exposure on TB development in Taiwanese adults. Methods: We included 46 196 adult participants from three rounds (2001, 2005, 2009) of the Taiwan National Health Interview Survey. Alcohol consumption was classified into heavy, regular, social, or never alcohol use. Heavy alcohol consumption was defined as intoxication at least once/week. Alcohol consumption and other covariates were collected by in-person interviews at baseline. Incident cases of active TB were identified from the National Health Insurance database. Multivariate logistic regression was used to estimate the association between alcohol consumption and active TB, with adjustment for age, sex, smoking, socioeconomic status, and other covariates. Results: A total of 279 new cases of active TB occurred during the study follow-up period. Heavy (adjusted odds ratio [AOR], 5.21; 95% confident interval [CI], 2.41-11.26) and regular alcohol use (AOR, 1.73; 95% CI, 1.26-2.38) were associated with higher risks of incident TB after adjusting for the subject demographics and comorbidities. Moreover, a strong dose-response effect was observed between increasing alcohol consumption and incident TB (AOR, 2.26; 95% CI, 1.59-3.21; P <.001). Conclusion: Heavy and regular alcohol consumption were associated with higher risks of active TB. Future TB control programs should consider strategies to lower the overall level of alcohol consumption to reduce the TB disease burden.

Keywords: alcohol consumption, tuberculosis, risk factor, cohort study

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Authors: A. A. Agbor, Jean Joel R. Bigna, Serges Clotaire Billong, Mathurin Cyrille Tejiokem, Gabriel L. Ekali, Claudia S. Plottel, Jean Jacques N. Noubiap, Hortence Abessolo, Roselyne Toby, Sinata Koulla-Shiro

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Background: Contributors to fatal outcomes in patients undergoing tuberculosis (TB) treatment in the setting of HIV co-infection are poorly characterized, especially in sub-Saharan Africa. Our study’s aim was to assess factors associated with death in TB/HIV co-infected patients during the first 6 months their TB treatment. Methods: We conducted a tertiary-care hospital-based retrospective cohort study from January 2006 to December 2013 at the Yaoundé Central Hospital, Cameroon. We reviewed medical records to identify hospitalized co-infected TB/HIV patients aged 15 years and older. Death was defined as any death occurring during TB treatment, as per the World Health Organization’s recommendations. Logistic regression analysis identified factors associated with death. Magnitudes of associations were expressed by adjusted odds ratio (aOR) with 95% confidence interval. A p value < 0.05 was considered statistically significant. Results: The 337 patients enrolled had a mean age of 39.3 (+/- 10.3) years and more (54.3%) were women. TB treatment outcomes included: treatment success in 60.8% (n=205), death in 29.4% (n=99), not evaluated in 5.3% (n=18), loss to follow-up in 5.3% (n=14), and failure in 0.3% (n=1) . After exclusion of patients lost to follow-up and not evaluated, death in TB/HIV co-infected patients during TB treatment was associated with: a TB diagnosis made before national implementation of guidelines regarding initiation of antiretroviral therapy (aOR = 2.50 [1.31-4.78]; p = 0.006), the presence of other AIDS-defining infections (aOR = 2.73 [1.27-5.86]; p = 0.010), non-AIDS comorbidities (aOR = 3.35 [1.37-8.21]; p = 0.008), not receiving co-trimoxazole prophylaxis (aOR = 3.61 [1.71-7.63]; p = 0.001), not receiving antiretroviral therapy (aOR = 2.45 [1.18-5.08]; p = 0.016), and CD4 cell counts < 50 cells/mm3 (aOR = 16.43 [1.05-258.04]; p = 0.047). Conclusions: The success rate of anti-tuberculosis treatment among hospitalized TB/HIV co-infected patients in our setting is low. Mortality in the first 6 months of treatment was high and strongly associated with specific clinical factors including states of greater immunosuppression, highlighting the urgent need for targeted interventions, including provision of anti-retroviral therapy and co-trimoxazole prophylaxis in order to enhance patient outcomes.

Keywords: TB/HIV co-infection, death, treatment outcomes, factors

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Authors: Sheikha Turki Alketbi

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Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.

Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML

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Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Alireza Mahmoudi Nasab, Tim Bakker

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Introduction: Mycobacterium tuberculosis (MTB) is the most intelligent bacterium that existed in the world to our best knowledge. This bacterium can cause tuberculosis (TB) which is responsible for its spread speed and murder of millions of people around the world. MTB has the practical function to escape from anti-tuberculosis drugs (AT), for this purpose, it handles some mutations in the main genes and creates new patterns for inhibited genes. Method and materials: Researchers have their best tries to safely isolate MTB from the sputum specimens of 35 patients in some hospitals in the Tehran province and detect MTB by culture on Löwenstein-Jensen (LJ) medium and microscopic examination. DNA was extracted from the established bacterial colony by enzymatic extraction method. It was amplified by the polymerase chain reaction (PCR) method, reverse hybridization, and evaluation for detection of resistance genes; generally, researchers apply GenoType MTBDRplus assay. Results: Investigations of results declare us that 21 of the isolated specimens (about 60%) have mutation in rpoB gene, which resisted to rifampicin (most prevalence), and 8 of them (about 22.8%) have mutation in katG or inhA genes which resisted to isoniazid. Also, 4 of them (about 11.4%) don't have any mutation, and 2 of them (about 5.7%) have mutation in every three genes, which makes them resistant to the two drugs mentioned above. Conclusion: Rifampicin and isoniazid are two essential AT that using in the first line of treatment. Resistance in rpoB, and katG, and inhA genes related to mentioned drugs lead to ineffective treatment.

Keywords: mycobacterium tuberculosis, tuberculosis, drug resistance, isoniazid, rifampicin

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Authors: Zainab A. Alaghbri, Labiba A., Esam A.

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Tuberculosis (TB) is the fourth leading cause of death in Yemen and is considered a major priority by the Ministry of Public Health. The war in Yemen has led to the emergence of one of the worst humanitarian crises in the world. These circumstances may lead to exacerbate the situation of tuberculosis. This study aims to describe the trend and incidence of TB in north and east governorates, Yemen 2019-2021 and provide recommendations for interventions. A descriptive analysis was conducted during July to September 2022. Data of TB cases were obtained from the national tuberculosis program as soft copy. The Data included the TB case collected and diagnosed during 2019-2021. The data contains the following variables: Sex, age, governorates, smear-positive cases, extra-pulmonary cases, and treatment outcomes. 16791 TB cases were notified for an overall case notification rate 65.5/100000 for all forms (smear positive and Extra-pulmonary), There was a slightly declined in 2020 and 2021 by 1%. Both the pulmonary smear positive and Extra pulmonary rates were slightly decreased from 8.8 to 7.7 and 13.5 to 12.8 / 100, 000 populations respectively. For Tuberculosis cases by type of patient, the incidence of extra-pulmonary was the highest (12,9, 11.3 and 12,2/100000) over the three years. However, the incidence of pulmonary failure was the lowest. The majority of cases were in the age group 25-34. The overall treatment success rate for smear-positive patients was 88%. Of the 627 patients with documented unsuccessful outcomes (e.g., failure, death, and default), 165 (23%) died, 52 (8.3%) failed treatment, and 410 (65%) defaulted. Overall, the magnitude of tuberculosis decreased over the periods reviewed. The proportion of Extra-pulmonary TB was the highest. The success rate achieved after treatment was below the levels established by the WHO End Tuberculosis Strategy (90%). Failure to complete treatment may be responsible for the low success rate. Monitoring and addressing the risk factors that were associated with treatment outcomes and duration may help improve the likelihood of achieving favorable outcomes among cases of smear-positive pulmonary TB.

Keywords: tuberculosis, trend, incidence, yemen

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Authors: Aneta Nitsch-Osuch, Beata Pawlus, Maria Pawlak

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Introduction: Recently, the number of parents who refuse to vaccinate their children or present so-called hesitant behaviors has increased in many developed countries. The study aimed to analyze the completeness and timeliness of vaccinations against hepatitis B and tuberculosis in neonates in a single maternity hospital in Warsaw (Poland). Material and Methods: We analyzed medical records of children born in the hospital between 1st January 2015 and 31st December 2016 and calculated the proportion of newborns not vaccinated on time. Results: The percentage of unvaccinated newborns was similar in the analyzed years: 7.2% in 2015 and 6.7% in 2016. Parental decisions rather than medical contraindications caused non-immunization (4.3% vs. 2.9% in 2015, and 4.7% vs. 2% in 2016). Most parents refused both vaccinations (81%-84%), whereas 7-8% refused only hep B vaccination, and 9-11% refused alone tuberculosis vaccination. The majority of hesitant parents decided to delay both vaccinations (70-80%), while 10-11% of parents chose to delay only one vaccination (hep B). In consecutive years, an increase in the percentage of parents delaying tuberculosis vaccination was reported (10 vs. 19%). Discussion: The increase in the number of newborns who are not correctly vaccinated just after birth due to their parents' decision should be considered non-gradual, both for hepatitis B and tuberculosis. It is necessary to implement effective educational and informative measures targeted at future parents to reinforce positive attitudes towards vaccinations and to dispel doubts about them among parents who are hesitant.

Keywords: hepatitis B, tuberculosis, immunization, new-borns, coverage rate

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Authors: D. A. Dakul, T. M. Akindigh, B. J. Dogonyaro, O. J. Abba, K. T. Tangtur, N. Sambo, J. A. E. Okopi, J. A. Yohanna, G. E. Imade, G. S. Mwansat, S. Oguche

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Malaria and urinary Schistosomaisis are both endemic in Nigeria and pose a serious health challenge in rural areas where co-infections are common. This descriptive cross sectional study was carried out to determine the prevalence of co-infection and the impact of concurrent infection on haemoglobin concentration, Eosinophil and CD4+ T-lymphocyte counts. Plasmodium falciparum and Schistosoma haematobium infection were determined by Malaria Rapid Diagnostic Test (MRDT) kits and the presence of visible haematuria respectively and confirmed by conventional Polymerase Chain Reaction (cPCR). P values < 0.05 were considered statistically significant. Of the 110 children examined, 13 (11.8%) had concurrent infection with Schistosoma haematobium falciparum, 46(41.8%) had Plasmodium falciparum infection while 16(14.5%) had Schistosoma haematobium infection. A strong association between co-infection and the ages of 10-15 years with a 36.4% prevalence of anaemia was observed. Malaria was significantly associated with anaemia than with concurrent infections or schistomiasis alone. Co-infection with both pathogens and a high prevalence of anaemia was observed in Jinduut community. Although the causes of anaemia are multi-factorial, further investigation into the extent to which malaria and urinary schistosomiasis contribute to anaemia is needed. Also, integrated control efforts must be strengthened to mitigate the impact of concurrent infection in this group of vulnerable members in the community. The results can be applied to other communities during control.

Keywords: co-Infection, plasmodium falciparum and scistosoma haematobium, Jinduut, Nigeria

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Authors: Sadek A. Makhlouf, Hassan M. Nouh

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Bone hydatidosis is an infection in worldwide distribution. Although there is no evidence in literature on Bone Hydatid disease in Libya, we tried to present the first epidemiological study of this disease in Eastern Libya through retrospective study from 1995 to 2013. Our data were collected from 3 hospitals in Eastern Libya particularly the sheep-raising areas with total number of musculoskeletal infection cases of two thousand one hundred ninety-four (2,194). There were five (5) five cases of bone infection, four (4) of it have been diagnosed after more than three (3) months. Our study is comparable to other international study but this type of bone infection need further studies for effective control strategies for all dogs to avoid serious complications that might happened from the delay in diagnosing this type of disease.

Keywords: bone infection, hydatidosis, Eastern Libya, sheep-raising areas

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Authors: Sonam Kumari

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, possesses a remarkable feature of entering into and emerging from a persistent state. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes.Mtb has seven such proteins (WhiB1 to WhiB7).WhiB proteins are transcriptional regulators; their conserved C-terminal HTH motif is involved in DNA binding. They regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical Analysis of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: tuberculosis, WhiB proteins, mycobacterium tuberculosis, nucleic acid binding

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Authors: Vandna Raghuvanshi, Vikrant Thakur, Anupam Jhobta

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Objective: To design HRCT criterion to forecast the threat of pulmonary tuberculosis. Material and methods: This was a prospective study of 69 patients with clinical suspicion of pulmonary tuberculosis. We studied their medical characteristics, numerous separate HRCT-results, and a combination of HRCT findings to foresee the danger for PTB by utilizing univariate and multivariate investigation. Temporary HRCT diagnostic criteria were planned in view of these outcomes to find out the risk of PTB and tested these criteria on our patients. Results: The results of HRCT chest were analyzed, and Rank was given from 1 to 4 according to the HRCT chest findings. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Rank 1: Highly suspected PTB. Rank 2: Probable PTB Rank 3: Nonspecific or difficult to differentiate from other diseases Rank 4: Other suspected diseases • Rank 1 (Highly suspected TB) was present in 22 (31.9%) patients, all of them finally diagnosed to have pulmonary tuberculosis. The sensitivity, specificity, and negative likelihood ratio for RANK 1 on HRCT chest was 53.6%, 100%, and 0.43, respectively. • Rank 2 (Probable TB) was present in 13 patients, out of which 12 were tubercular, and 1 was non-tubercular. • The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the combination of Rank 1 and Rank 2 was 82.9%, 96.4%, 23.22, and 0.18, respectively. • Rank 3 (Non-specific TB) was present in 25 patients, and out of these, 7 were tubercular, and 18 were non-tubercular. • When all these 3 ranks were considered together, the sensitivity approached 100% however, the specificity reduced to 35.7%. The positive likelihood ratio and negative likelihood ratio were 1.56 and 0, respectively. • Rank 4 (Other specific findings) was given to 9 patients, and all of these were non-tubercular. Conclusion: HRCT is useful in selecting individuals with greater chances of pulmonary tuberculosis.

Keywords: pulmonary, tuberculosis, multivariate, HRCT

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Authors: Mark Andrew Tu, Raymond Olazo, Cybele Abad

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Cryptococcosis is an invasive infection most commonly found in patients who are immuno compromised. However, patients with this infection usually present with meningitis and rarely pulmonary infection in isolation. We present a case of a Filipino HIV patient who developed cryptococcal pneumonia without meningitis.

Keywords: Cryptococcal Pneumonia, HIV, Filipino, immune system

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Authors: Juan Santos Garcia

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Introduction: Tuberculosis is a chronic granulomatous disease caused by a microorganism called Mycobacterium tuberculosis, it has the capacity to spread from the lungs to other parts of the body. Globally, the rate per 100 thousand inhabitants has varied from 136 in 2007 to 122 in 2012; while in the region of the Americas has been much lower: 32 cases per 100,000 in 2007, to 29 in 2012. In El Salvador have also varied incidence rates from 2007 to 2012, from 27.4 cases per 100 000 population to 32 in the period indicated. Methods: Screening was performed with smear and chest X-ray at 80 military personnel from Military Brigade # 5 of El Salvador. Besides HIV tests were taken at the positive cases, which are also made interview, investigating demographic, clinical, laboratory and risk factors data. Frequencies, percentages and rates were calculated using Excel page. The rates were calculated for each of the 5 military bedrooms (called A, B, C, D, and E). Results: Attack rate was 18.75% in the bedroom C. the index case was identified and two secondary cases, with an exposure period of 59 days. Only the index case presented symptoms: cough, fever and weight loss. The other two cases had no symptoms. Discussion: We found a rate of tuberculosis 526 times higher than the national rate. He was also 12.5 times higher than that found in other studies in closed populations such as school facilities. It was not possible to make association analysis.

Keywords: tuberculosis, outbreak, military brigade, chronic granulomatous disease

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Authors: Gil Soriano, Aubreyrose Casilang

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Soil-transmitted helminth infection remains to be one of the leading public health problem worldwide, which is common in the rural developing regions especially among children. This study aimed to detect the presence of soil transmitted helminths among children and its associated transmission factors. Descriptive cross sectional research was the design used in the study and questionnaires were administered. Stool samples were collected among the samples (n=108) and were analyzed using kato thick method. Results showed that 61 out of 108 respondents are infected by soil transmitted helminth infection with A. lumbricoides the highest, followed by hookworm and T. trichuria. Parent's educational attainment, hand washing practices, and water sources were found to be associated with presence of Soil Transmitted Helminth infection.

Keywords: associated risk factors, barangay, school children, soil transmitted helminth infection

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Authors: Sunita Gakkhar, Arti Mishra

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In this paper, a nonlinear host vector model has been proposed and analyzed for the two strain dengue dynamics incorporating ADE effect. The model considers that the asymptomatic infected people are more responsible for secondary infection than that of symptomatic ones and differentiates between them. The existence conditions are obtained for various equilibrium points. Basic reproduction number has been computed and analyzed to explore the effect of secondary infection enhancement parameter on dengue infection. Stability analyses of various equilibrium states have been performed. Numerical simulation has been done for the stability of endemic state.

Keywords: dengue, ade, stability, threshold, asymptomatic, infection

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Authors: Li Yuchen, Wu Qingxin, Jin Yuxing, Yang Qian

Abstract:

Interleukin-11 (IL-11), a well-known anti-inflammatory factor, helps to protect against intestinal epithelium damage caused by physical or chemical factors. However, little is known about the role of IL-11 during viral infection. Herein, high mRNA and protein levels of IL-11 were found in epithelial cells and jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, and IL-11 expression was positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) suppressed PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 inhibited viral infection by preventing PEDV-mediated apoptosis of cells through activating the IL-11/STAT3 signal pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggested that that IL-11 is a novel PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential uses of IL-11 as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.

Keywords: Interleukin-11, Porcine epidemic diarrhea virus, STAT3, anti-apoptosis

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Authors: M. Kuzhko, M. Gumeniuk, D. Butov, T. Tlustova, O. Denysov, T. Sprynsian

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Background: The aim of the research was to determine the effectiveness of chemotherapy using intravenous antituberculosis drugs compared with their oral administration during the intensive phase of treatment. Methods: 152 tuberculosis patients were randomized into 2 groups: Main (n=65) who received isoniazid, ethambutol and sodium rifamycin intravenous + pyrazinamide per os and control (n=87) who received all the drugs (isoniazid, rifampicin, ethambutol, pyrazinamide) orally. Results: After 2 weeks of treatment symptoms of intoxication disappeared in 59 (90.7±3.59 %) of patients of the main group and 60 (68.9±4.9 %) patients in the control group, p<0.05. The mean duration of symptoms of intoxication in patients main group was 9.6±0.7 days, in control group – 13.7±0.9 days. After completing intensive phase sputum conversion was found in all the patients main group and 71 (81.6±4.1 %) patients control group p < 0.05. The average time of sputum conversion in main group was 1.6±0.1 months and 1.9±0.1 months in control group, p > 0.05. In patients with destructive pulmonary tuberculosis time to sputum conversion was 1.7±0.1 months in main group and 2.2±0.2 months in control group, p < 0.05. The average time of cavities healing in main group was 2.9±0.2 months and 3.9±0.2 months in the control group, p < 0.05. Conclusions: In patients with newly diagnosed destructive pulmonary tuberculosis use of isoniazid, ethambutol and sodium rifamycin intravenous in the intensive phase of chemotherapy resulted in a significant reduction in terms of the disappearance of symptoms of intoxication and sputum conversion.

Keywords: intravenous chemotherapy, tuberculosis, treatment efficiency, tuberculosis drugs

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Authors: Maryam Vaezjalali, Foad Davoodbeglou, Mehrnaz Mesdaghi, Hossein Goudarzi, Fariba Shojaei, Hourieh Aram

Abstract:

Introduction: Hepatitis B virus (HBV) infection causes chronic infection in human population, with high mortality. Some people are more susceptible to this infection. One of the high risk communities is mentally retarded children, who are institutionalized. Special conditions in these centers predispose children for HBV infection and transmission to healthy people. In this study our objective was to determine the prevalence of HBV infection among institutionalized mentally retarded children and study its associated risk factors. Materials and methods: In this study, 250 mentally retarded children (younger than 14 years old) were included. They were living in 5 nursing institutions, located in different parts of Tehran. HBsAg was measured in the sera of these patients by ELISA method. Results: Among 250 children, 20 children (8%) were HBsAg positive. HBV infection in girls was more than boys (11% to 5.6%). Among the types of mental retardation, children with cerebral palsy had the highest positive result for HBsAg. The most HBV infection (28.5%) was seen in children with longest duration of being institutionalized (10 to 11 years). Vaccinated children were more HBsAg positive (8.7%) than non-vaccinated children (5.3%). However, no significant relationship was observed between any of these factors and HBsAg positivity. Conclusion: Despite improvement of people’s health condition and implementation of HBV vaccination, the prevalence of HBV infection is high in institutionalized mentally retarded children, which highlights the need for active measures to reduce this infection among this high risk population.

Keywords: hepatitis B virus, HBV vaccine, intellectually disabled children, mentally retarded

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

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Background and Objective: Hematopoietic stem cell transplantation (HSCT) has been widely used for treating oncological and hematological diseases. Although HSCT has helped to improve patient survival, the risk of developing an infection during hospitalization is an important cause of morbidity and mortality. This study aimed to analyze the infection profile during hospitalization and the associated risk factors among patients undergoing autologous HSCT at the University Hospital, Shahid Ghazi Tabatabaei Hospital, Tabriz, Iran. Subjects and Methods: This was a cross-sectional study on patients undergoing autologous HSCT at a public university hospital. Methods: Patients with febrile neutropenia between 2015 and 2018 were retrospectively evaluated regarding their infection profile and associated risk factors. This survey included: bacterial culture and blood culture on specific media. Results: Infection occurred in 57.2% of 56 patients with febrile neutropenia. The main source of infection was the central venous catheter (25.9%). Infection was chiefly due to Gram-positive bacteria, although Gram-negative-related infections were more severe and caused a higher death rate. Sex, age, skin color, nutritional status, and underlying disease were not associated with the development of infection. Patients with severe mucositis (Grades III and IV) had a higher infection rate (P < 0.001). Patients who developed pulmonary complications during hospitalization had higher infection rates (P = 0.002). Infection was the main cause of death (57.1%) in the study sample. Conclusion: Strategies aimed at reducing infection-related mortality rates among patients undergoing autologous HSCT are necessary.

Keywords: hematopoietic stem cell, autologous bone marrow transplantation, infection profile, tabriz, Iran

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Authors: Syed Asif Hassan, Syed Atif Hassan

Abstract:

Multidrug-resistant Tuberculosis (MDR-TB) is an infection caused by the resistant strains of Mycobacterium tuberculosis that do not respond either to isoniazid or rifampicin, which are the most important anti-TB drugs. The increase in the occurrence of a drug-resistance strain of MTB calls for an intensive search of novel target-based therapeutics. In this context LprG (Rv1411c) a lipoprotein from MTB plays a pivotal role in the immune evasion of Mtb leading to survival and propagation of the bacterium within the host cell. Therefore, a machine learning method will be developed for generating a computational model that could predict for a potential anti LprG activity of the novel antituberculosis compound. The present study will utilize dataset from PubChem database maintained by National Center for Biotechnology Information (NCBI). The dataset involves compounds screened against MTB were categorized as active and inactive based upon PubChem activity score. PowerMV, a molecular descriptor generator, and visualization tool will be used to generate the 2D molecular descriptors for the actives and inactive compounds present in the dataset. The 2D molecular descriptors generated from PowerMV will be used as features. We feed these features into three different classifiers, namely, random forest, a deep neural network, and a recurring neural network, to build separate predictive models and choosing the best performing model based on the accuracy of predicting novel antituberculosis compound with an anti LprG activity. Additionally, the efficacy of predicted active compounds will be screened using SMARTS filter to choose molecule with drug-like features.

Keywords: antituberculosis drug, classifier, machine learning, molecular descriptors, prediction

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