Search results for: respiratory tuberculosis

Authors: S. B. R. Slagmulder

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Monitoring inspiratory effort and dynamic lung stress in patients on pressure support ventilation in the ICU is important for protecting against self inflicted lung injury (P-SILI) and diaphragm dysfunction. Strategies to address the detrimental effects of respiratory drive and effort can lead to improved patient outcomes. Two non-invasive estimation methods, occlusion pressure (Pocc) and P0.1, have been proposed for achieving lung and diaphragm protective ventilation. However, their relationship and interpretation in neuro ICU patients is not well understood. P0.1 is the airway pressure measured during a 100-millisecond occlusion of the inspiratory port. It reflects the neural drive from the respiratory centers to the diaphragm and respiratory muscles, indicating the patient's respiratory drive during the initiation of each breath. Occlusion pressure, measured during a brief inspiratory pause against a closed airway, provides information about the inspiratory muscles' strength and the system's total resistance and compliance. Research Objective: Understanding the relationship between Pocc and P0.1 in brain-injured patients can provide insights into the interpretation of these values in pressure support ventilation. This knowledge can contribute to determining extubation readiness and optimizing ventilation strategies to improve patient outcomes. The central goal is to asses a study protocol for determining the relationship between Pocc and P0.1 in brain-injured patients on pressure support ventilation and their ability to predict successful extubation. Additionally, comparing these values between brain-damaged and non-brain-damaged patients may provide valuable insights. Key Areas of Inquiry: 1. How do Pocc and P0.1 values correlate within brain injury patients undergoing pressure support ventilation? 2. To what extent can Pocc and P0.1 values serve as predictive indicators for successful extubation in patients with brain injuries? 3. What differentiates the Pocc and P0.1 values between patients with brain injuries and those without? Methodology: P0.1 and occlusion pressures are standard measurements for pressure support ventilation patients, taken by attending doctors as per protocol. We utilize electronic patient records for existing data. Unpaired T-test will be conducted to compare P0.1 and Pocc values between both study groups. Associations between P0.1 and Pocc and other study variables, such as extubation, will be explored with simple regression and correlation analysis. Depending on how the data evolve, subgroup analysis will be performed for patients with and without extubation failure. Results: While it is anticipated that neuro patients may exhibit high respiratory drive, the linkage between such elevation, quantified by P0.1, and successful extubation remains unknown The analysis will focus on determining the ability of these values to predict successful extubation and their potential impact on ventilation strategies. Conclusion: Further research is pending to fully understand the potential of these indices and their impact on mechanical ventilation in different patient populations and clinical scenarios. Understanding these relationships can aid in determining extubation readiness and tailoring ventilation strategies to improve patient outcomes in this specific patient population. Additionally, it is vital to account for the influence of sedatives, neurological scores, and BMI on respiratory drive and occlusion pressures to ensure a comprehensive analysis.

Keywords: brain damage, diaphragm dysfunction, occlusion pressure, p0.1, respiratory drive

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Authors: Reena K., Mamatha H. G., Somshekarayya, P. Kumar

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Objectives: The annual proficiency testing of intermediate reference laboratories is conducted by the National Reference Laboratory (NRL) to assess the efficiency of the laboratories to correctly identify Mycobacterium tuberculosis and to determine its drug susceptibility pattern. The proficiency testing results from 2013 to 2017 were analyzed to determine laboratories that were consistent in reporting quality results and those that had difficulty in doing so. Methods: A panel of twenty cultures were sent out to each of these laboratories. The laboratories were expected to grow the cultures in their own laboratories, set up drug susceptibly testing by all the methods they were certified for and report the results within the stipulated time period. The turnaround time for reporting results, specificity, sensitivity positive and negative predictive values and efficiency of the laboratory in identifying the cultures were analyzed. Results: Most of the laboratories had reported their results within the stipulated time period. However, there was enormous delay in reporting results from few of the laboratories. This was mainly due to improper functioning of the biosafety level III laboratory. Only 40% of the laboratories had 100% efficiency in solid culture using Lowenstein Jensen medium. This was expected as a solid culture, and drug susceptibility testing is not used for diagnosing drug resistance. Rapid molecular methods such as Line probe assay and Genexpert are used to determine drug resistance. Automated liquid culture system such as the Mycobacterial growth indicator tube is used to determine prognosis of the patient while on treatment. It was observed that 90% of the laboratories had achieved 100% in the liquid culture method. Almost all laboratories had achieved 100% efficiency in the line probe assay method which is the method of choice for determining drug-resistant tuberculosis. Conclusion: Since the liquid culture and line probe assay technologies are routinely used for the detection of drug-resistant tuberculosis the laboratories exhibited higher level of efficiency as compared to solid culture and drug susceptibility testing which are rarely used. The infrastructure of the laboratory should be maintained properly so that samples can be processed safely and results could be declared on time.

Keywords: annual proficiency testing, drug susceptibility testing, intermediate reference laboratory, national reference laboratory

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Authors: Afia Naheed, Manmohan Singh, David Lucy

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This work is based on a mathematical as well as statistical study of an SEIJTR deterministic model for the interpretation of transmission of severe acute respiratory syndrome (SARS). Based on the SARS epidemic in 2003, the parameters are estimated using Runge-Kutta (Dormand-Prince pairs) and least squares methods. Possible graphical and numerical techniques are used to validate the estimates. Then effect of the model parameters on the dynamics of the disease is examined using sensitivity and uncertainty analysis. Sensitivity and uncertainty analytical techniques are used in order to analyze the affect of the uncertainty in the obtained parameter estimates and to determine which parameters have the largest impact on controlling the disease dynamics.

Keywords: infectious disease, severe acute respiratory syndrome (SARS), parameter estimation, sensitivity analysis, uncertainty analysis, Runge-Kutta methods, Levenberg-Marquardt method

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Authors: Richa Sharma, Uma Nahar, Sadhna Sharma, Indu Verma

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Counteracting the deadly pathogen Mycobacterium tuberculosis (M. tb) effectively is still a global challenge. Scrutinizing alternative weapons like antimicrobial peptides to strengthen existing tuberculosis artillery is urgently required. Considering the antimycobacterial potential of Human Beta Defensin 1 (HBD-1) along with isoniazid, the present study was designed to explore the ability of HBD-1 to act against active and dormant M. tb. HBD-1 was screened in silico using antimicrobial peptide prediction servers to identify its short antimicrobial motif. The activity of both HBD-1 and its selected motif (Pep B) was determined at different concentrations against actively growing M. tb in vitro and ex vivo in monocyte derived macrophages (MDMs). Log phase M. tb was grown along with HBD-1 and Pep B for 7 days. M. tb infected MDMs were treated with HBD-1 and Pep B for 72 hours. Thereafter, colony forming unit (CFU) enumeration was performed to determine activity of both peptides against actively growing in vitro and intracellular M. tb. The dormant M. tb models were prepared by following two approaches and treated with different concentrations of HBD-1 and Pep B. Firstly, 20-22 days old M. tbH37Rv was grown in potassium deficient Sauton media for 35 days. The presence of dormant bacilli was confirmed by Nile red staining. Dormant bacilli were further treated with rifampicin, isoniazid, HBD-1 and its motif for 7 days. The effect of both peptides on latent bacilli was assessed by colony forming units (CFU) and most probable number (MPN) enumeration. Secondly, human PBMC granuloma model was prepared by infecting PBMCs seeded on collagen matrix with M. tb(MOI 0.1) for 10 days. Histopathology was done to confirm granuloma formation. The granuloma thus formed was incubated for 72 hours with rifampicin, HBD-1 and Pep B individually. Difference in bacillary load was determined by CFU enumeration. The minimum inhibitory concentrations of HBD-1 and Pep B restricting growth of mycobacteria in vitro were 2μg/ml and 20μg/ml respectively. The intracellular mycobacterial load was reduced significantly by HBD-1 and Pep B at 1μg/ml and 5μg/ml respectively. Nile red positive bacterial population, high MPN/ low CFU count and tolerance to isoniazid, confirmed the formation of potassium deficienybaseddormancy model. HBD-1 (8μg/ml) showed 96% and 99% killing and Pep B (40μg/ml) lowered dormant bacillary load by 68.89% and 92.49% based on CFU and MPN enumeration respectively. Further, H&E stained aggregates of macrophages and lymphocytes, acid fast bacilli surrounded by cellular aggregates and rifampicin resistance, indicated the formation of human granuloma dormancy model. HBD-1 (8μg/ml) led to 81.3% reduction in CFU whereas its motif Pep B (40μg/ml) showed only 54.66% decrease in bacterial load inside granuloma. Thus, the present study indicated that HBD-1 and its motif are effective antimicrobial players against both actively growing and dormant M. tb. They should be further explored to tap their potential to design a powerful weapon for combating tuberculosis.

Keywords: antimicrobial peptides, dormant, human beta defensin 1, tuberculosis

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Authors: Ananya Gupta, Sangeeta Bhaskar

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Mycobacterium indicus pranii (MIP) is a saprophytic mycobacterium. It is a predecessor of M. avium complex (MAC). Whole genome analysis and growth kinetics studies have placed MIP in between pathogenic and non-pathogenic species. It shares significant antigenic repertoire with M. tuberculosis and have unique immunomodulatory properties. MIP provides better protection than BCG against pulmonary tuberculosis in animal models. Immunization with MIP by aerosol route provides significantly higher protection as compared to immunization by subcutaneous (s.c.) route. However, mechanism behind differential protection has not been studied. In this study, using mice model we have evaluated and compared the M.tb specific immune response in lung compartments (airway lumen / lung interstitium) as well as spleen following MIP immunization via nasal (i.n.) and s.c. route. MIP i.n. vaccination resulted in increased seeding of memory T cells (CD4+ and CD8+ T-cells) in the airway lumen. Frequency of CD4+ T cells expressing Th1 migratory marker (CXCR3) and activation marker (CD69) were also high in airway lumen of MIP i.n. group. Significantly high ex vivo secretion of cytokines- IFN-, IL-12, IL-17 and TNF- from cells of airway luminal spaces provides evidence of antigen-specific lung immune response, besides generating systemic immunity comparable to MIP s.c. group. Analysis of T cell response on per cell basis revealed that antigen specific T-cells of MIP i.n. group were functionally superior as higher percentage of these cells simultaneously secreted IFN-gamma, IL-2 and TNF-alpha cytokines as compared to MIP s.c. group. T-cells secreting more than one of the cytokines simultaneously are believed to have robust effector response and crucial for protection, compared with single cytokine secreting T-cells. Adoptive transfer of airway luminal T-cells from MIP i.n. group into trachea of naive B6 mice revealed that MIP induced CD8 T-cells play crucial role in providing long term protection. Thus the study demonstrates that MIP intranasal vaccination induces M.tb specific memory T-cells in the airway lumen that results in an early and robust recall response against M.tb infection.

Keywords: airway lumen, Mycobacterium indicus pranii, Th1 migratory markers, vaccination

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Authors: Cheng-Yu Tsai, Wen-Te Liu, Yin-Tzu Lin, Chen-Chen Lo, Kang Lo

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Background: Driving drowsiness related to inadequate or disordered sleep accounts for a major percentage of traffic accidents. Sleep-disordered breathing (SDB) syndrome is a common respiratory disorder during sleep. However, the effects of SDB syndrome on driving fatigue remain unclear. Objective: This study aims to investigate the relationship between SDB pattern and driving drowsiness. Methodologies: The physical condition while driving was obtained from the questionnaires to classify the state of driving fatigue. SDB syndrome was quantified as the polysomnography, and the air flow pattern was collected by the thermistor and nasal pressure cannula. To evaluate the desaturation, the mean hourly number of greater than 3% dips in oxygen saturation was sentenced by reregistered technologist during examination in a hospital in New Taipei City (Taiwan). The independent T-test was used to investigate the correlations between sleep disorders related index and driving drowsiness. Results: There were 880 subjects recruited in this study, who had been done polysomnography for evaluating severity for obstructive sleep apnea syndrome (OSAS) as well as completed the driver condition questionnaire. Four-hundred-eighty-four subjects (55%) were classified as fatigue group, and 396 subjects (45%) were served as the control group. Significantly higher values of snoring index (242.14 ± 205.51 /hours) were observed in the fatigue group (p < 0.01). The value of respiratory disturbance index (RDI) (31.82 ± 19.34 /hours) in fatigue group were significantly higher than the control group (p < 0.01). Conclusion: We observe the considerable association between SDB syndrome and driving drowsiness. To promote traffic safety, SDB syndrome should be controlled and alleviated.

Keywords: driving drowsiness, sleep-disordered breathing syndrome, snoring index, respiratory disturbance index.

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Authors: Jakub Młoźniak, Adam Szymański, Gabriela Stondzik, Dagny Krankowska, Tomasz Mikuła

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Nontuberculous mycobacteria (NTM) are bacterial species that cause diversely manifesting diseases mainly in immunocompromised patients. In people with HIV, NTM infection is an AIDS-defining disease and usually appears when the lymphocyte T CD4 count is below 50 cells/μl. The usage of antiretroviral therapy has decreased the prevalence of NTM among people with HIV, but the disease can still be observed especially among patients with late HIV diagnosis. Common presence in environment, human colonization, clinical similarity with tuberculosis and slow growth on culture makes NTM especially hard to diagnose. The study aimed to analyze the epidemiology and clinical course of NTM among patients with HIV. This study included patients with NTM and HIV admitted to our department between 2017 and 2023. Medical records of patients were analyzed and data on age, sex, median time from HIV diagnosis to identification of NTM infection, median CD4 count at NTM diagnosis, methods of determining NTM infection, type of species of mycobacteria identified, clinical symptoms and treatment course were gathered. Twenty-four patients (20 men, 4 women) with identified NTM were included in this study. Among them, 20 were HIV late presenters. The patients' median age was 40. The main symptoms which patients presented were fever, weight loss and cough. Pulmonary disease confirmed with positive cultures from sputum/bronchoalveolar lavage was present in 18 patients. M. avium was the most common species identified. M. marinum caused disseminated skin lesions in 1 patient. Out of all, 5 people were not treated for NTM caused by lack of symptoms and suspicion of colonization with mycobacterium. Concomitant tuberculosis was present in 6 patients. The median diagnostic time from HIV to NTM infections was 3.5 months. The median CD4 count at NTM identification was 69.5 cells/μl. Median NTM treatment time was 16 months but 7 patients haven’t finished their treatment yet. The most commonly used medications were ethambutol and clarithromycin. Among analyzed patients, 4 of them have died. NTM infections are still an important disease among patients who are HIV late presenters. This disease should be taken into consideration during the differential diagnosis of fever, weight loss and cough in people with HIV with lymphocyte T CD4 count <100 cells/μl. Presence of tuberculosis does not exclude nontuberculous mycobacterium coinfection.

Keywords: mycobacteriosis, HIV, late presenter, epidemiology

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Authors: Katharigatta N. Venugopala, Melendhran Pillay, Bander E. Al-Dhubiab

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Tuberculosis (TB) infection is caused mainly by Mycobacterium tuberculosis (MTB) and it is one of the most threatening and wide spread infectious diseases in the world. Benzothiazole derivatives are found to have diverse chemical reactivity and broad spectrum of pharmacological activity. Some of the important pharmacological activities shown by the benzothiazole analogues are antitumor, anti-inflammatory, antimicrobial, anti-tubercular, anti-leishmanial, anticonvulsant and anti-HIV properties. Keeping all these facts in mind in the present investigation it was envisaged to synthesize a series of novel {2-(benzo[d]-thiazol-2-yl-methoxy)-substitutedaryl}-(substitutedaryl)-methanones (4a-f) and characterize by IR, NMR (1H and 13C), HRMS and single crystal x-ray studies. The title compounds are investigated for in vitro anti-tubercular activity against two TB strains such as H37Rv (ATCC 25177) and MDR-MTB (multi drug resistant MTB resistant to Isoniazid, Rifampicin and Ethambutol) by agar diffusion method. Among the synthesized compounds in the series, test compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone (2c) was found to exhibit significant activity with MICs of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively when compared to standard drugs. Single crystal x-ray studies was used to study intra and intermolecular interactions, including polymorphism behavior of the test compounds, but none of the compounds exhibited polymorphism behavior.

Keywords: benzothiazole analogues, characterization, crystallography, anti-TB activity

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Authors: Arundhuti Devi, Gitumani Devi, Krishna G. Bhattacharyya

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The goal of this study was to assess the characteristics of the airborne dust created by opencast coal mining and its relation to population hospitalization risk for skin and lung diseases in Margherita Coalfield, Assam, India. Air samples were collected for 24 h in three 8-h periods. For the collection of particulate matter (PM10) and total suspended particulate matter (SPM) samples, respiratory dust samplers with glass microfiber filter papers were used. PM10 was analyzed for Cu, Cd, Cr, Mn, Zn, Ni, Fe and Pb with Flame Atomic Absorption Spectrophotometer (FAAS). SPM and PM10 concentrations were respectively found to be as high as 1,035 and 265.85 μg/m³ in work zone air. The concentration of metals associated with PM10 showed values higher than the permissible limits. It was observed that the average concentrations of the metals Fe, Pb, Ni, Zn, and Cu were very high during the winter month of December, those of Cd and Cr were high during the month of May and Mn was high during February. The morphology of the particles studied with scanning electron microscopy (SEM) gave significant results. Due to opencast coal mining, the air in the work zone, as well as the general ambient air, was found to be highly polluted with respect to dust. More than 8000 patient records maintained by the hospital authority were collected from three hospitals in the area. The highest percentage of people suffering from lung diseases are found in Margherita Civil Hospital (~26.77%) whereas most people suffering from skin diseases reported for treatment in the ESIC hospital (47.47%). Both PM10 and SPM were alarmingly high, and the results were in conformity with the high incidence of lung and other respiratory diseases in the study area.

Keywords: heavy metals, open cast coal mining, PM10, respiratory diseases

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Authors: Manoj Kumar Reddy Pulim, Lakshmi Muthukrishnan, Geetha Jayapathy, Radhika Raman

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Introduction: In the past two decades, noninvasive positive pressure ventilation (NIPPV) emerged as one of the most important advances in the management of both acute and chronic respiratory failure in children. In the acute setting, it is an alternative to intubation with a goal to preserve normal physiologic functions, decrease airway injury, and prevent respiratory tract infections. There is a need to determine the clinical profile and parameters which point towards the need for NIV in the pediatric emergency setting. Objectives: i) To study the clinical profile of children who required non invasive ventilation and invasive ventilation, ii) To study the clinical parameters common to children who required non invasive ventilation. Methods: All children between one month to 18 years, who were intubated in the pediatric emergency department and those for whom decision to commence Non Invasive Ventilation was made in Emergency Room were included in the study. Children were transferred to the Paediatric Intensive Care Unit and started on Non Invasive Ventilation as per our hospital policy and followed up in the Paediatric Intensive Care Unit. Clinical profile of all children which included age, gender, diagnosis and indication for intubation were documented. Clinical parameters such as respiratory rate, heart rate, saturation, grunting were documented. Parameters obtained were subject to statistical analysis. Observations: Airway disease (Bronchiolitis 25%, Viral induced wheeze 22%) was a common diagnosis in 32 children who required Non Invasive Ventilation. Neuromuscular disorder was the common diagnosis in 27 children (78%) who were Intubated. 17 children commenced on Non Invasive Ventilation who later needed invasive ventilation had Neuromuscular disease. High frequency nasal cannula was used in 32, and mask ventilation in 17 children. Clinical parameters common to the Non Invasive Ventilation group were age < 1 year (17), tachycardia n = 7 (22%), tachypnea n = 23 (72%) and severe respiratory distress n = 9 (28%), grunt n = 7 (22%), SPO2 (80% to 90%) n = 16. Children in the Non Invasive Ventilation + INTUBATION group were > 3 years (9), had tachycardia 7 (41%), tachypnea 9(53%) with a male predominance n = 9. In statistical comparison among 3 groups,'p' value was significant for pH, saturation, and use of Ionotrope. Conclusion: Invasive ventilation can be avoided in the paediatric Emergency Department in children with airway disease, by commencing Non Invasive Ventilation early. Intubation in the pediatric emergency department has a higher association with neuromuscular disorders.

Keywords: clinical parameters, indications, non invasive ventilation, paediatric emergency room

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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: Man Wai Leung, Margaret O’Donoghue, Lorna K. P. Suen

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Personal and household hygiene measures are important to prevent upper respiratory tract infections (URTIs) and other infectious diseases, including coronavirus disease 2019 (COVID-19). An online survey recruited 414 eligible parents in Hong Kong to study their hygiene knowledge, attitudes, and practices (KAP) in the prevention of URTIs among their children. The average knowledge score was high (10.2/12.0), but some misconceptions were identified. The majority of participants agreed that good personal hygiene (93.5%) and good environmental hygiene (92.8%) can prevent URTIs. The average score for hand hygiene practices was high (3.78/4.00), but only 56.8% of parents always perform hand hygiene before touching their mouth, nose, or eyes. For environmental hygiene, only some household items were disinfected with disinfectants (69.8%: door handles, 60.4%: toilet seats, 42.8%: floor, 24.2%: dining chairs, 20.5%: dining tables). Higher knowledge score was associated with parents having a tertiary educational level or above, working as healthcare professionals, living at private residential flat or staff quarter, and having a household income of $70,000 or above. Hand hygiene practices varied significantly with parents’ age and income. During the 5th wave of the COVID-19 epidemic, misconceptions about hygiene knowledge were found among parents. Health promotion programs should target parents, especially those who are in old age, obtain lower educational levels, live in public housing, or have a lower income. Hand hygiene moments and proper use of disinfectants could be one of the targeted educational topics.

Keywords: hygiene, upper respiratory tract infection, parents, children, COVID-19

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Authors: C. Scurr, J. Jeans, S. Srivastava

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Introduction: Acute type two respiratory failure (T2RF) has become a common presentation over the last two decades primarily due to an increase in the prevalence of chronic lung disease. Acute exacerbations can be managed either medically or in combination with non-invasive ventilation (NIV) which should be monitored with regular arterial blood gas samples (ABG). Arterial lines allow more frequent arterial blood sampling with less patient discomfort. We present the experience from a teaching hospital emergency department (ED) and level 2 medical high-dependency unit (HDU) that together form the pathway for management of acute type 2 respiratory failure. Methods: Patients acutely presenting to Charing Cross Hospital, London, with T2RF requiring non-invasive ventilation (NIV) over 14 months (2011 to 2012) were identified from clinical coding. Retrospective data collection included: demographics, co-morbidities, blood gas numbers and timing, if arterial lines were used and who performed this. Analysis was undertaken using Microsoft Excel. Results: Coding identified 107 possible patients. 69 notes were available, of which 41 required NIV for type 2 respiratory failure. 53.6% of patients had an arterial line inserted. Patients with arterial lines had 22.4 ABG in total on average compared to 8.2 for those without. These patients had a similar average time to normalizing pH of (23.7 with arterial line vs 25.6 hours without), and no statistically significant difference in mortality. Arterial lines were inserted by Foundation year doctors, Core trainees, Medical registrars as well as the ICU registrar. 63% of these were performed by the medical registrar rather than ICU, ED or a junior doctor. This is reflected in that the average time until an arterial line was inserted was 462 minutes. The average number of ABGs taken before an arterial line was 2 with a range of 0 – 6. The average number of gases taken if no arterial line was ever used was 7.79 (range of 2-34) – on average 4 times as many arterial punctures for each patient. Discussion: Arterial line use was associated with more frequent arterial blood sampling during each inpatient admission. Additionally, patients with an arterial line have less individual arterial punctures in total and this is likely more comfortable for the patient. Arterial lines are normally sited by medical registrars, however this is normally after some delay. ED clinicians could improve patient comfort and monitoring thus allowing faster titration of NIV if arteral lines were regularly inserted in the ED. We recommend that ED doctors insert arterial lines when indicated in order improve the patient experience and facilitate medical management.

Keywords: non invasive ventilation, arterial blood gas, acute type, arterial line

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Authors: Susan Scott, Dina Hanna, Bassel Zebian, Gary Ruiz, Sreena Das

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Although the number of cases of TB in England has fallen over the last 4 years, it remains an important public health burden with 1 in 20 cases dying annually. The vast majority of cases present in non-UK born individuals with social risk factors. We present a case of non-pulmonary TB presenting in a healthy child born in the UK to professional parents. We present a case of a healthy 10 year old boy who developed acute back pain during school PE. Over the next 5 months, he was seen by various health and allied professionals with worsening back pain and kyphosis. He became increasing unsteady and for the 10 days prior to admission to our hospital, he developed fevers. He was admitted to his local hospital for tonsillitis where he suffered two falls on account of his leg weakness. A spinal X-ray revealed a pathological fracture and gibbus formation. He was transferred to our unit for further management. On arrival, the patient had lower motor neurone signs of his left leg. He underwent spinal fixture, laminectomy and decompression. Microbiology samples taken intra-operatively confirmed Mycobacterium Tuberculosis. He had a positive Mantoux and T-spot and treatment were commenced. There was no evidence of immune compromise. The patient was born in the UK, had a BCG scar and his only travel history had been two years prior to presentation when he travelled to the Phillipines for a short holiday. The patient continues to have issues around neuropathic pain, mobility, pill burden and mild liver side effects from treatment. Discussion: There is a paucity of case reports on spinal TB in paediatrics and diagnosis is often difficult due to the non-specific symptomatology. Although prognosis on treatment is good, a delayed diagnosis can have devastating consequences. This case highlights the continued need for higher index of suspicion and diagnosis in a world with changing patterns of migration and increase global travel. Surgical intervention is limited to the most serious cases to minimise further neurological damage and improve prognosis. There remains the need for a multi-disciplinary approach to deal with challenges of treatment and rehabilitation.

Keywords: tuberculosis, non-pulmonary TB, public health burden, diagnostic challenge

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Authors: Swati Gautam, Amita Jain, Shyampyari Jaiswar

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Objective: To elucidate the role of (ApaI&TaqI) VDR gene polymorphism in the pathogenesis of female genital tuberculosis (FGTB) cases. Background: Female genital TB represents about 15-20% of total extra-pulmonary TB (EPTB). Female subjects with vitamin D deficiency have been shown to be at higher risk of pulmonary TB as well as FGTB. In same context few functional polymorphism in vitamin D receptor (VDR) gene has been considered as an important genetic risk factor that modulate the development of FGTB. Therefore we aimed, to elucidate the role of (ApaI&TaqI) VDR gene polymorphism in the pathogenesis of FGTB. Study design: Case-Control study. Sample size: Cases (60) and Controls (60). Study site: Department of Obstetrics & Gynecology & Department of Microbiology, K.G.M.U. Lucknow, (UP). Inclusion criteria: Cases: Women with age group 20-35 years, premenstrual endometrial aspiration collected and included in the study, those were positive with acid-fast bacilli (AFB)/ TB-PCR/ LJ culture/ liquid culture. Controls: Women with age group 20-35 years having no history of ATT and all test negative for TB recruited as control. Exclusion criteria: -Women with endometriosis, polycystic ovaries (PCOD), positive on Chlamydia & gonorrhea, already on anti-tubercular therapy (ATT) excluded. Materials and Methods: Blood samples were collected in EDTA tubes from cases and controls stored at -20ºC. Genomic DNA extraction was carried out by salting-out method. Genotyping of VDR gene (ApaI&TaqI) polymorphism was performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 2% agarose gel. Statistical analysis was done by SPSS16.3 software & computing odds ratio (OR) with 95% CI. Results: Increased risk of female genital tuberculosis was observed in AA genotype (OR =1.1419-6.212 95% CI, P*<0.036) and A allele (OR =1.255-3.518, 95% CI, P* < 0.006) in FGTB as compared to controls. Moreover A allele was found more frequent in FGTB patients. No significant difference was observed in TaqI gene polymorphism of VDR gene. Conclusion: The ApaI polymorphism is significantly associated with etiology of FGTB and plays an important role as a genetic risk factor in FGTB women.

Keywords: ARMS, ATT, EPTB, FGTB, VDR

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Authors: Hancy Issac, Gerben Keijzers, Ian Yang, Clint Moloney, Jackie Lea, Melissa Taylor

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Introduction: Chronic obstructive pulmonary disease guideline non-adherence is associated with a reduction in health-related quality of life in patients (HRQoL). Improving guideline adherence has the potential to mitigate fragmented care thereby sustaining pulmonary function, preventing acute exacerbations, reducing economic health burdens, and enhancing HRQoL. The development of an electronic proforma stemming from expert consensus, including digital guideline resources and direct interdisciplinary referrals is hypothesised to improve guideline adherence and patient outcomes for emergency department (ED) patients with COPD. Aim: The aim of this study was to develop consensus among ED and respiratory staff for the correct composition of a COPD electronic proforma that aids in guideline adherence and management in the ED. Methods: This study adopted a mixed-method design to develop the most important indicators of care in the ED. The study involved three phases: (1) a systematic literature review and qualitative interdisciplinary staff interviews to assess barriers and solutions for guideline adherence and qualitative interdisciplinary staff interviews, (2) a modified Delphi panel to select interventions for the proforma, and (3) a consensus process through three rounds of scoring through a quantitative survey (ED and Respiratory consensus) and qualitative thematic analysis on each indicator. Results: The electronic proforma achieved acceptable and good internal consistency through all iterations from national emergency department and respiratory department interdisciplinary experts. Cronbach’s alpha score for internal consistency (α) in iteration 1 emergency department cohort (EDC) (α = 0.80 [CI = 0.89%]), respiratory department cohort (RDC) (α = 0.95 [CI = 0.98%]). Iteration 2 reported EDC (α = 0.85 [CI = 0.97%]) and RDC (α = 0.86 [CI = 0.97%]). Iteration 3 revealed EDC (α = 0.73 [CI = 0.91%]) and RDC (α = 0.86 [CI = 0.95%]), respectively. Conclusion: Electronic proformas have the potential to facilitate direct referrals from the ED leading to reduced hospital admissions, reduced length of hospital stays, holistic care, improved health care and quality of life and improved interdisciplinary guideline adherence.

Keywords: COPD, electronic proforma, modified delphi study, interdisciplinary, guideline adherence, COPD-X plan

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Authors: Sonia Mannan

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A qualitative study was conducted in a rural area of the southwestern region of Bangladesh to identify perceptions, practices, and the role of first-time mothers surrounding acute respiratory infections (ARI) in infants and children aged under four years. The study reveals that all mothers had knowledge of ARI and were able to identify a number of signs and symptoms. They also recognized pneumonia and thought it to be caused by exposure to cold or weather change, supernatural causes, evil influences, mothers’ negligence, and failure to observe ‘purdah’. They were able to identify chest retractions, difficult breathing, and inability to feed as signs of severe disease needing treatment outside the home. In these cases, spiritual healers were sought, and allopathic treatment was delayed or avoided. Home care practices involved massaging the child with oil and avoiding 'cooling' foods, including water. With the presence of fever and breathing difficulty, mothers tended to increase the number and diversity of medicines, although more concern was expressed about fever than about breathing difficulty. Effective medical care was more likely to be delayed for infants than for older children (they often waited 2-5 days after signs of illness appeared); infants were also more likely to be taken to a spiritual healer as the first-choice provider. The reasons for these perceptions and practices and their implications on the ARI of infants and young children are discussed. Community intervention is identified as viable, effective, and practical to address the body of local socio-cultural knowledge about family practices and the role of the mother regarding the mitigation of ARI in infants and young children.

Keywords: acute respiratory infections , public health, pneumonia, Bangladesh

Procedia PDF Downloads 86

Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

Procedia PDF Downloads 157

Authors: Turki M. Habeebullah, Atef M. F. Mohammed, Essam A. Morsy

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In recent decades, particulate matter (PM10) have received much attention due to its potential adverse health impact and the subsequent need to better control or regulate these pollutants. The aim of this paper is focused on study risk assessment of PM10 in four different districts (Shebikah, Masfalah, Aziziyah, Awali) in Makkah, Saudi Arabia during the period from 1 Ramadan 1434 AH - 27 Safar 1435 AH. samples was collected by using Low Volume Sampler (LVS Low Volume Sampler) device and filtration method for estimating the total concentration of PM10. The study indicated that the mean PM10 concentrations were 254.6 (186.1 - 343.2) µg/m3 in Shebikah, 184.9 (145.6 - 271.4) µg/m3 in Masfalah, 162.4 (92.4 - 253.8) µg/m3 in Aziziyah, and 56.0 (44.5 - 119.8) µg/m3 in Awali. These values did not exceed the permissible limits in PME (340 µg/m3 as daily average). Furthermore, health assessment is carried out using AirQ2.2.3 model to estimate the number of hospital admissions due to respiratory diseases. The cumulative number of cases per 100,000 were 1534 (18-3050 case), which lower than that recorded in the United States, Malaysia. The concentration response coefficient was 0.49 (95% CI 0.05 - 0.70) per 10 μg/m3 increase of PM10.

Keywords: air pollution, respiratory diseases, airQ2.2.3, Makkah

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Authors: Nermeen Elbeltagy, Helmy abd Elsatar, Sara Hassan, Mohamed Darwish

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Introduction: with the inial appearance in Wuhan, China, in December 2019, the coronavirus disease-related respiratory infection (COVID-19) has rapidly spread among people all over the world. The WHO considered it a pandemic in March 2020. The severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have proved that pregnant females as well as their fetuses are exposed to adverse outcomes, including high rates of intensive care unit (ICU) admission and case fatality. Physiological changes occurring during pregnancy such as the increased transverse diameter of the thoracic cage as well as the elevation of the diaphragm can expose the mother to severe infections because of her decreased tolerance for hypoxia. Furthermore, vasodilation and changes in lung capacity can cause mucosal edema and an increase in upper respiratory tract secretions. In addition, the increased susceptibility to infection is enhanced by changes in cellmediated immunity. Aim of the work: to study the effect of COVID-19 on pregnant females admitted to El-Shatby Maternity University Hospital regarding maternal antepartum, intrapartum and postpartum adverse effects on the mothers and their neonates. Method: A retrospective cohort study was done between October 2020 and October 2022. Maternal characteristics and associated health conditions of COVID-19 positive parents were investigated. Also, the severity of their conditions and me of infection (first or second or third trimester)were explored. Cases were diagnosed based on presence of symptoms suggestive of COVID-19, laboratory tests (other than PCR) and radiological findings.all cases were confirmed by positive PCR test results. Results: The most common adverse maternal outcomes were pre-term labor (11.6%) followed by premature rupture of membranes (5.7%), post-partum hemorrhage (5.4%), preeclampsia (5.0%) and placental abrupon (4.3%). One sixth of the neonates of the studied paents were admied to NICUs and 6.5% of them had respiratory distress with no neonatal deaths. The majority of neonates (85.4%) had a birth weight of 2500- 4000g (normal range). Most of the neonates (77.9%) had an APGAR score of equal or more than 7 in 5 minutes. Conclusion: the most common comorbidity that might increase the incidence of COVID-19 before pregnancy were diabetes, cardiac disorders/ chronic hypertension and chronic obstructive lung diseases (non-asthma). During pregnancy, anemia followed by gestational diabetes and pre-eclampsia/gestational hypertension were the most prevalent comorbidity. So, severity of infection can be reduced by good antenatal care.

Keywords: COVID-19, pregnancy outcome, complicated pregnancy., COVID in Egypt

Procedia PDF Downloads 48

Authors: Staci McGill, Morgan Hayes, Robert Coleman, Kimberly Tumlin

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The interaction and relationships between horses and humans have been shown to be positive for physical, mental, and emotional wellbeing, however equine spaces where these interactions occur do include some environmental risks. There are 1.7 million jobs associated with the equine industry in the United States in addition to recreational riders, owners, and volunteers who interact with horses for substantial amounts of time daily inside built structures. One specialized facility, an “indoor arena” is a semi-indoor structure used for exercising horses and exhibiting skills during competitive events. Typically, indoor arenas have a sand or sand mixture as the footing or surface over which the horse travels, and increasingly, silica sand is being recommended due to its durable nature. It was previously identified in a semi-qualitative survey that the majority of individuals using indoor arenas have environmental concerns with dust. 27% (90/333) of respondents reported respiratory issues or allergy-like symptoms while riding with 21.6% (71/329) of respondents reporting these issues while standing on the ground observing or teaching. Frequent headaches and/or lightheadedness was reported in 9.9% (33/333) of respondents while riding and in 4.3% 14/329 while on the ground. Horse respiratory health is also negatively impacted with 58% (194/333) of respondents indicating horses cough during or after time in the indoor arena. Instructors who spent time in indoor arenas self-reported more respiratory issues than those individuals who identified as smokers, highlighting the health relevance of understanding these unique structures. To further elucidate environmental concerns and self-reported health issues, 35 facility assessments were conducted in a cross-sectional sampling design in the states of Kentucky and Ohio (USA). Data, including air speeds, were collected in a grid fashion at 15 points within the indoor arenas and then mapped spatially using krigging in ARCGIS. From the spatial maps, standard variances were obtained and differences were analyzed using multivariant analysis of variances (MANOVA) and analysis of variances (ANOVA). There were no differences for the variance of the air speeds in the spaces for facility orientation, presence and type of roof ventilation, climate control systems, amount of openings, or use of fans. Variability of the air speeds in the indoor arenas was 0.25 or less. Further analysis yielded that average air speeds within the indoor arenas were lower than 100 ft/min (0.51 m/s) which is considered still air in other animal facilities. The lack of air movement means that dust clearance is reliant on particle size and weight rather than ventilation. While further work on respirable dust is necessary, this characterization of the semi-indoor environment where animals and humans interact indicates insufficient air flow to eliminate or reduce respiratory hazards. Finally, engineering solutions to address air movement deficiencies within indoor arenas or mitigate particulate matter are critical to ensuring exposures do not lead to adverse health outcomes for equine professionals, volunteers, participants, and horses within these spaces.

Keywords: equine, indoor arena, ventilation, particulate matter, respiratory health

Procedia PDF Downloads 81

Authors: Gabriela Wyszogrodzka, Przemyslaw Dorozynski, Barbara Gil, Maciej Strzempek, Bartosz Marszalek, Piotr Kulinowski, Wladyslaw Piotr Weglarz, Elzbieta Menaszek

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MOFs (Metal-Organic Frameworks) belong to a new group of porous materials with a hybrid organic-inorganic construction. Their structure is a network consisting of metal cations or clusters (acting as metallic centers, nodes) and the organic linkers between nodes. The interest in MOFs is primarily associated with the use of their well-developed surface and large porous. Possibility to build MOFs of biocompatible components let to use them as potential drug carriers. Furthermore, forming MOFs structure from cations possessing paramagnetic properties (e.g. iron cations) allows to use them as MRI (Magnetic Resonance Imaging) contrast agents. The concept of formation of particles that combine the ability to transfer active substance with imaging properties has been called theranostic (from words combination therapy and diagnostics). By building MOF structure from iron cations it is possible to use them as theranostic agents and monitoring the distribution of the active substance after administration in real time. In the study iron-MOF: Fe-MIL-101-NH2 was chosen, consisting of iron cluster in nodes of the structure and amino-terephthalic acid as a linker. The aim of the study was to investigate the possibility of applying Fe-MIL-101-NH2 as inhalable theranostic particulate system for the first-line anti-tuberculosis antibiotic – isoniazid. The drug content incorporated into Fe-MIL-101-NH2 was evaluated by dissolution study using spectrophotometric method. Results showed isoniazid encapsulation efficiency – ca. 12.5% wt. Possibility of Fe-MIL-101-NH2 application as the MRI contrast agent was demonstrated by magnetic resonance tomography. FeMIL-101-NH2 effectively shortening T1 and T2 relaxation times (increasing R1 and R2 relaxation rates) linearly with the concentrations of suspended material. Images obtained using multi-echo magnetic resonance imaging sequence revealed possibility to use FeMIL-101-NH2 as positive and negative contrasts depending on applied repetition time. MOFs micronization via ultrasound was evaluated by XRD, nitrogen adsorption, FTIR, SEM imaging and did not influence their crystal shape and size. Ultrasonication let to break the aggregates and achieve very homogeneously looking SEM images. MOFs cytotoxicity was evaluated in in vitro test with a highly sensitive resazurin based reagent PrestoBlue™ on L929 fibroblast cell line. After 24h no inhibition of cell proliferation was observed. All results proved potential possibility of application of ironMOFs as an isoniazid carrier and as MRI contrast agent in inhalatory treatment of tuberculosis. Acknowledgments: Authors gratefully acknowledge the National Science Center Poland for providing financial support, grant no 2014/15/B/ST5/04498.

Keywords: imaging agents, metal-organic frameworks, theranostics, tuberculosis

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Authors: Tamrat Girma Biru

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Multidrug-resistant tuberculosis (MDR-TB) is defined as resistant to at least Refampicin and Isoniazed: the most two power full TB drugs. It is a leading cause of high rates of morbidity and mortality, and increasing psychosocial challenges to patients, especially when co-infected with Human Immunodeficiency Virus (HIV). Ethiopia faces the highest rates of MDR-TB infection in the world. Objectives: The main objective of this study was to identify the psychosocial challenges of MDR-TB patients, to investigate the extent of the psychosocial challenges on (self-esteem, depression, and stigma) that MDR-TB patients encounter, to examine whether there is a sex difference in experiencing psychosocial challenges and assess the counseling needs of MDR-TB patients. Methodology: A cross-sectional study was conducted at St. Peter TB Specialized Hospital, Addis Ababa on 40 patients (25 males and 15 females) who are hospitalized for treatment. The patients were identified by using purposive sampling and made fill a questionnaire measuring their level of self-esteem, depression and stigma. Besides, data were collected from 16 participants, 28 care providers and 8 guardians, using semi-structured interview. The obtained data were analyzed using SPSS statistical program, descriptive statistics, independent t-test, and qualitative description. Results and Discussion: The results of the study showed that the majority (80%) of the respondents had suffered psychological challenges and social discriminations. Thus, the significance of MDR-TB and its association with HIV/AIDS problems is considered. Besides the psychosocial challenges, various aggravating factors such as length of treatment, drug burden and insecurity in economy together highly challenges the life of patients. In addition, 60% of participants showed low level of self-esteem. The patients also reported that they experienced high self-stigma and stigma by other members of the society. The majority of the participants (75%) showed moderate and severe level of depression. In terms of sex there is no difference between the mean scores of males and females in the level of depression and stigmatization by others and by themselves. But females showed lower level of self-esteem than males. The analysis of the t-test also shows that there were no statistically significant sex difference on the level of depression and stigma. Based on the qualitative data MDR-TB patients face various challenges in their life sphere such as: Psychological (depression, low self value, lowliness, anxiety), social (stigma, isolation from social relations, self-stigmatization,) and medical (drug side effect, drug toxicity, drug burden, treatment length, hospital stays). Recommendations: Based on the findings of this study possible recommendations were forwarded: develop and extend MDR-TB disease awareness creation through by media (printing and electronic), school net TB clubs, and door to door community education. Strengthen psychological wellbeing and social relationship of MDR-TB patients using proper and consistent psychosocial support and counseling. Responsible bodies like Ministry of Health (MOH) and its stakeholders and Non Governmental Organizations (NGOs) need to assess the challenges of patients and take measures on this pressing issue.

Keywords: psychosocial challenges, counseling, multi-drug resistant tuberculosis (MDR-TB), tuberculosis therapy

Procedia PDF Downloads 363

Authors: J. K. D. M. P. Madara, R. B. L. Dharmawickreme, Linu John, Ivee Boiss

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Flemingia vestita, commonly known as ‘Sohphlang’ is an important medicinal plant found in the North-Eastern region of India, which is traditionally recognized for its anthelmintic properties. This study was aimed to evaluate the phytochemical constituents and antibacterial activity of the tuber skin extracts of the plant species. Methanol, acetone, and water were used to obtain the solvent extractions of the skin peel extracts. Concentrated extracts of skin peel were tested using previously established qualitative phytochemical assays. The antibacterial efficacy of methanol tuber skin extract was tested against Gram-negative and positive microorganisms, namely, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Mycobacterium tuberculosis strains. Agar well diffusion method was employed to determine the zone of inhibition of the plant extracts. Obtained data were statistically analyzed. Methanol extracts of Flemingia vestita were found to be effective against Bacillus subtilis and Mycobacterium tuberculosis at concentrations of 0.5 mg/ml. The reported zone of inhibition for the two strains was 13.3mm ± 0.57 and 16.3mm ± 4.9, respectively. However Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were resistant to the plant extracts with no zone of inhibition. Alkaloids, glycosides, and phenols were found to be present in aqueous, methanol, and acetone extracts of the plant in qualitative phytochemical analysis.

Keywords: flemingia vestita, antibacterial activity, phytochemical screening, well diffusion method

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Authors: Jineetkumar Gawad, Chandrakant Bonde

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Tuberculosis (TB) is a major worldwide concern whose control has been exacerbated by HIV, the rise of multidrug-resistance (MDR-TB) and extensively drug resistance (XDR-TB) strains of Mycobacterium tuberculosis. The interest for newer and faster acting antitubercular drugs are more remarkable than any time. To search potent compounds is need and challenge for researchers. Here, we tried to design lead for inhibition of Decaprenyl phosphoryl-β-D-ribose 2′-epimerase (DprE1) enzyme. Arabinose is an essential constituent of mycobacterial cell wall. DprE1 is a flavoenzyme that converts decaprenylphosphoryl-D-ribose into decaprenylphosphoryl-2-keto-ribose, which is intermediate in biosynthetic pathway of arabinose. Latter, DprE2 converts keto-ribose into decaprenylphosphoryl-D-arabinose. We had a selection of 23 compounds from azaindole series for computational study, and they were drawn using marvisketch. Ligands were prepared using Maestro molecular modeling interface, Schrodinger, v10.5. Common pharmacophore hypotheses were developed by applying dataset thresholds to yield active and inactive set of compounds. There were 326 hypotheses were developed. On the basis of survival score, ADRRR (Survival Score: 5.453) was selected. Selected pharmacophore hypotheses were subjected to virtual screening results into 1000 hits. Hits were prepared and docked with protein 4KW5 (oxydoreductase inhibitor) was downloaded in .pdb format from RCSB Protein Data Bank. Protein was prepared using protein preparation wizard. Protein was preprocessed, the workspace was analyzed using force field OPLS 2005. Glide grid was generated by picking single atom in molecule. Prepared ligands were docked with prepared protein 4KW5 using Glide docking. After docking, on the basis of glide score top-five compounds were selected, (5223, 5812, 0661, 0662, and 2945) and the glide docking score (-8.928, -8.534, -8.412, -8.411, -8.351) respectively. There were interactions of ligand and protein, specifically HIS 132, LYS 418, TRY 230, ASN 385. Pi-pi stacking was observed in few compounds with basic Imidazo [4,5-b] pyridine ring. We had basic azaindole ring in parent compounds, but after glide docking, we received compounds with Imidazo [4,5-b] pyridine as a basic ring. That might be the new lead in the process of drug discovery.

Keywords: DprE1 inhibitors, in silico drug designing, imidazo [4, 5-b] pyridine, lead, tuberculosis

Procedia PDF Downloads 128

Authors: N. Anand, P. S. Nayyer, V. Rana, S. Verma

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Background: Diabetes mellitus is a group of disorders characterized by hyperglycemia and associated with microvascular and macrovascular complications. Among the lesser known complications is the involvement of respiratory system. Changes in pulmonary volume, diffusion and elastic properties of lungs as well as the performance of the respiratory muscles lead to a restrictive pattern in lung functions. The present study was aimed to determine the changes in various parameters of pulmonary function tests amongst patients with Type 2 Diabetes Mellitus and also try to study the effect of duration of Diabetes Mellitus on pulmonary function tests. Methods: It was a cross sectional study performed at Dr Baba Saheb Ambedkar Hospital and Medical College in, Delhi, A Tertiary care referral centre which included 200 patients divided into 2 groups. The first group included diagnosed patients with diabetes and the second group included controls. Cases and controls symptomatic for any acute or chronic Respiratory or Cardiovascular illness or a history of smoking were excluded. Both the groups were subjected to spirometry to evaluate for the pulmonary function tests. Result: The mean Forced Vital Capacity (FVC), Forced Expiratory Volume in first second (FEV1), Peak Expiratory Flow Rate(PEFR) was found to be significantly decreased ((P < 0.001) as compared to controls while the mean ratio of Forced Expiratory Volume in First second to Forced Vital Capacity was not significantly decreased( p>0.005). There was no correlation seen with duration of the disease. Conclusion: Forced Vital Capacity (FVC), Forced Expiratory Volume in first second (FEV1), Peak Expiratory Flow Rate(PEFR) were found to be significantly decreased in patients of Diabetes mellitus while ratio of Forced Expiratory Volume in First second to Forced Vital Capacity (FEV1/FVC) was not significantly decreased. The duration of Diabetes mellitus was not found to have any statistically significant effect on Pulmonary function tests (p > 0.005).

Keywords: diabetes mellitus, pulmonary function tests, forced vital capacity, forced expiratory volume in first second

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Authors: Albina V. Moskvicheva, Gevorg G. Kazarian, Anna R. Valeeva, Marina A. Efimova, Malik N. Mukminov, Eduard A. Shuralev, Rustam Kh. Ravilov, Kamil S. Khaertynov

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Improving the early diagnosis of tuberculosis and solving a number of problems associated with the differential diagnosis of Mycobacterium bovis infection, nonspecific tuberculin reactions caused by sensitization of the body by non-tuberculosis mycobacteria, is urgent. The filtrates and extracts of M. bovis cell surface components are promising antigens with diagnostic potential. The purpose of this study was to isolate and characterize antigenic proteins and determine the dominant M. bovis antigens recognized by the humoral immune system. The mycobacterial cells were homogenized on FastPrep-24. Gel-filtration chromatography was used to fractionate the lysates of cell surface component extracts and proteins isolated from M. bovis culture supernatant. The separated fractions were analyzed using two-dimensional gel electrophoresis followed by determination of antigen serological activity using immunoblot with specific hyperimmune rabbit blood serum. As a result of electrophoretic separation of components by molecular weight, 23 antigen fractions were obtained. Analysis of densitograms showed that the fractions contained two zones of antigens with pronounced serological activity, corresponding to molecular weights of 28 and 21 kDa. The high serological activity of the 28 kDa antigen was established by immunoblot using hyperimmune blood sera. Separated and characterized by M. bovis specific antigen with a molecular weight of 28 kDa was added to the collection of specific marker antigens for M. bovis.

Keywords: antigen, gel-filtration chromatography, immunoblot, Mycobacterium bovis

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Authors: Vatsal M. Patel, Navin B. Patel

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The present studies deal with the developing a series bearing a diphenyl ethers nucleus using structure-based drug design concept. A newer series of diphenyl ether based azetidinone namely N-(3-chloro-2-oxo-4-(3-phenoxyphenyl)azetidin-1-yl)-2-(substituted amino)acetamide (2a-j) have been synthesized by condensation of m-phenoxybenzaldehyde with 2-(substituted-phenylamino)acetohydrazide followed by the cyclisation of resulting Schiff base (1a-j) by conventional method as well as microwave heating approach as a part of an environmentally benign synthetic protocol. All the synthesized compounds were characterized by spectral analysis and were screened for in vitro antimicrobial, antitubercular and antiprotozoal activity. The compound 2f was found to be most active M. tuberculosis (6.25 µM) MIC value in the primary screening as well as this same derivative has been found potency against L. mexicana and T. cruzi with MIC value 2.09 and 6.69 µM comparable to the reference drug Miltefosina and Nifurtimox. To provide understandable evidence to predict binding mode and approximate binding energy of a compound to a target in the terms of ligand-protein interaction, all synthesized compounds were docked against an enoyl-[acyl-carrier-protein] reductase of M. tuberculosis (PDB ID: 4u0j). The computational studies revealed that azetidinone derivatives have a high affinity for the active site of enzyme which provides a strong platform for new structure-based design efforts. The Lipinski’s parameters showed good drug-like properties and can be developed as an oral drug candidate.

Keywords: antimycobacterial, antiprotozoal, azetidinone, diphenylether, docking, microwave

Procedia PDF Downloads 133

Authors: Ayesha Ali, Emilia Lindquist, Arif Jalal, Hannah Yusuf, Kayan Cheung, Rowan Eastabrook

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It is currently estimated that over a third of deaths in children under five in Tanzania are caused by acute respiratory infections (ARIs). However, despite being one of the leading causes of morbidity and mortality across the developing world, its risk factors are poorly understood. Therefore, a systematic review of the literature published between 2015 and 2020 was conducted, focusing on risk factors for ARI in Tanzanian children under the age of five. 2015 Demographic and Health Survey (DHS) for Tanzania was analysed to supplement these findings with national data. 2224 papers were retrieved from two databases and were analysed by three independent reviewers. Thirteen papers were eligible for inclusion, covering a wide range of risk factors among which comorbidities (n=6), malnutrition (n=5), lack of parental education (n=4), poor socio-economic status (n=3), and delay in seeking healthcare (n=3) were the most cited risk factors. The risk factors with the highest reported risk ratios/odds ratios were lack of parental education (RR=11.5-14.5), followed by enrolment in school (RR=4.4), delay in seeking healthcare (RR=3.8) and cooking indoors (aOR =1.8-RR=5.5). The DHS data provided local context to these risk factors. For instance, the number of children experiencing symptoms of ARI in both urban and rural areas ranged between 4.5-5% in the two weeks prior to the survey. However, 79% of symptomatic children in Zanzibar received antibiotics for treatment compared to just 34% of those in the Southern Highlands. As demonstrated by both the systematic review and the DHS analysis, risk factors for ARI are predominantly socially determined, with Tanzania’s poorer rural children possessing the highest risk for ARI and more adverse health outcomes. Therefore, the burden of ARIs in Tanzanian children may be alleviated through the provision of appropriate treatment and parental education in rural areas.

Keywords: acute respiratory infection, child, health education, morbidity, mortality, pneumonia, Tanzania

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Authors: Vanphanom Sychareun, Viengnakhone Vongxay, Kongmany Chaleunvong, Pascale Hancart Petitet

Abstract:

Background: Lao PDR still has challenges in preventing and managing health against risk of emerging and re-emerging diseases, particularly HIV/AIDS, tuberculosis and malaria among pregnant women. Community-based intervention for mothers requires more evidences on awareness of such diseases and access to rapid diagnostic tests. The study aims to determine the awareness of pregnant women regarding HIV, TB and Malaria, the access to rapid diagnostic test of such diseases among pregnant women of local community and their factors related. Method: This is a cross sectional study using quantitative approach to explore the awareness of pregnant women on HIV/AIDS/TB and Malaria in Savannakhet province, Lao PDR in three remote districts (Phin, Thapangthong and Atsaphone) of Savannakhet province. The study targeted group was pregnant women at the community level. Sample size for primary data collection of pregnant women was 189. Face-to-face administered questionnaires were applied. Descriptive and inferential statistics were applied to determine the associated factors with awareness of pregnant women on HIV/AIDS/TB and Malaria. This study is under the HEALTH project/ Expertise France. Result: Most of our participants were pregnant at 28 – 42 weeks (50.3%); ranged 4 – 38 weeks. Mean age of pregnant women was 24.3 years old (range: 14 - 48 years old); 15.9% of whom were at age below 19 years. Around 94.2% of respondents works were farming, 54.5% were illiterate, 74.0% were Mon-Kmer ethnic, and 60% had income lower than average. Only 56.6% that have access to ANC, 39.1% started the access to ANC during the first trimester and only 19.6% had visited the ANC for at least four times. Almost pregnant women (and 92.1% and 93.1%) had low to moderate knowledge of HIV and TB respectively, while three-fourth of pregnant women (74.6%) had low to moderate knowledge of malaria. Slightly higher than half of participants (53.4% and 52.9%) had easy access to HIV and TB respectively ; while 72.5% had easy access to malaria. Majority of participants knew where to get tested for malaria (73.5%) and TB (54.5%), but 73.5% did not know where to get tested for HIV. Very few pregnant women (1.6%, 2.1% and 8.5%) experienced having tested for HIV/TB/malaria. respectively. Factors associated with awareness on HIV were occupation as staff, business (OR:5.9; 95% CI:1.2-28.1), upper secondary education (OR: 14.6; 95% CI:3.1-69.2); Mone-Khmer ethnic (OR: 0.4, 95% CI: 0.2-0.8); and attending ANC more than 4 times (OR:4.1, 95%:1.7-9.7). Factors associated with awareness on TB were occupation as staff, business (OR:2.4; 95% CI: 0.7-8.0), upper secondary education (OR: 6.2; 95% CI: 1.9-20.5); Mone-Khmer ethnic (OR: 0.5, 95% CI:0.3-0.9); attending ANC more than 4 times (OR:2.8, 95%:1.2-6.4). Factors associated with awareness on malaria were upper secondary education (OR: 18.1; 95% CI: 2.3-142.9); Mone-Khmer ethnic (OR: 0.2, 95% CI:0.1-0.4); attending ANC more than 4 times (OR:3.6, 95%:1.5-8.8). Conclusion: A very low awareness on HIV, TB and malaria among pregnant women in rural community of Savannakhet triggers the requirement of comprehensive public health intervention on awareness and access to prevention against emerging diseases for all pregnant women. Future intervention should focus on providing more knowledge to pregnant women during ANC and encouraging them to attend ANC more than 4 times.

Keywords: pregnant women, HIV, tuberculosis, malaria, awareness, Laos

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