Search results for: pulmonary tuberculosis

Authors: Jose Hernandez, Lina Martínez, Gustavo Gonzalez, Carlos Lázaro, Diana Castrillon, Jonathan Cardona, Laura Mejía, Yina Sanchez, Luisa Ochoa, Evert Jimenez

Abstract:

Objectives: Economic analyses of tuberculosis control interventions are usually focused on the payer’s perspective. To assess the overall economic impact of the disease, out-of-pocket and indirect costs are also required. This research is aimed to estimate overall economic impact under DOTS-strategy (Directly Observed Therapy Short Course). Methods: A cross-sectional survey of 91 adult tuberculosis patients in treatment for at least two months was conducted from the society perspective. A standardized questionnaire was used in three different cities of Colombia: Medellin (poverty is 17.7%), Monteria (poverty is 36.9%) and Quibdó (poverty is 51.2%). Costs were converted to 2013 USD and categorized into two periods: diagnostics phase and treatment. Results: The median cost during diagnostics was 13$ (±SD 9.5). The median monthly patient out-of-pocket costs during treatment were 32$ (±SD 6.8), equivalent to 17% of patient’s median monthly income, estimated in 186$ (±SD 23). Costs recorded in Medellin were 47$ in Monteria was 18$ and in Quibdó was 13$. Conclusion: Patient costs under DOTS strategy are high even when services are provided free of charge. The creation or strengthening of community-based treatment supervisors could greatly impact costs of tuberculosis and lower drop-outs.

Keywords: tuberculosis, costs and cost analysis, health promotion, Colombia

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Authors: Mattia Testuzza

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Public health is a social endeavour, which involves many different actors: from extremely stratified, structured health systems to unofficial networks of people and knowledge. Health and diseases are an intertwined individual and social experiences. Both patients and health workers navigate this public space through relations of trust. Trust in healthcare goes from the personal trust between a patient and her/his doctor to the trust of both the patient and the health worker in the medical knowledge and the healthcare system. Trust it is not a given, but it is continuously negotiated, given and gained. The key to understand these essential relations of trust in health is to recognise them as a social practice, which therefore implies agency and power. In these terms, health is constantly public and made public, as trust emerges as a meaningfully political phenomenon. Trust as a power relation can be observed at play in the implementation of public health policies such as the WHO’s Directly-Observed Theraphy Short-course (DOTS), and with the increasing concern for drug-resistance that tuberculosis pose, looking at the role of trust in the healthcare delivery system and implementation of public health policies becomes significantly relevant. The ethnographic fieldwork was carried out in four months through observation of the daily practices at the National Tuberculosis Center of Nepal, and semi-structured interviews with MultiDrug-Resistant Tuberculosis (MDR-TB) patients at different stages of the treatment, their relatives, MDR-TB specialised nurses, and doctors. Throughout the research, the role which trust plays in tuberculosis treatment emerged as one fundamental ax that cuts through all the different factors intertwined with drug-resistance development, unfolding a tension between the DOTS policy, which undermines trust, and the day-to-day healthcare relations and practices which cannot function without trust. Trust also stands out as a key component of the solutions to unforeseen issues which develop from the overall uncertainty of the context - for example, political instability and extreme poverty - in which tuberculosis treatment is carried out in Nepal.

Keywords: trust, tuberculosis, drug-resistance, politics of health

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Authors: Rachel F. Ajayi, Unathi Sidwaba, Usisipho Feleni, Samantha F. Douman, Ezo Nxusani, Lindsay Wilson, Candice Rassie, Oluwakemi Tovide, Priscilla G.L. Baker, Sibulelo L. Vilakazi, Robert Tshikhudo, Emmanuel I. Iwuoha

Abstract:

Pyrazinamide (PZA) is among the first-line pro-drugs in the tuberculosis (TB) combination chemotherapy used to treat Mycobacterium tuberculosis. Numerous reports have suggested that hepatotoxicity due to pyrazinamide in patients is due to inappropriate dosing. It is therefore necessary to develop sensitive and reliable techniques for determining the PZA metabolic profile of diagnosed patients promptly and at point-of-care. This study reports the determination of PZA based on nanobiosensor systems developed from disuccinimidyl octanedioate modified Cytochrome P450-2E1 (CYP2E1) electrodeposited on gold substrates derivatised with (poly(8-anilino-1-napthalene sulphonic acid) PANSA/PVP-AgNPs nanocomposites. The rapid and sensitive amperometric PZA detection gave a dynamic linear range of 2 µM to 16 µM revealing a limit of detection of 0.044 µM and a sensitivity of 1.38 µA/µM. The Michaelis-Menten parameters; KM, KMapp and IMAX were also calculated and found to be 6.0 µM, 1.41 µM and 1.51 µA respectively indicating a nanobiosensor suitable for use in serum.

Keywords: tuberculosis, cytochrome P450-2E1, disuccinimidyl octanedioate, pyrazinamide

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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: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: Ntandazo Dlatu, Benjamin Longo-Mbenza, Andre Renzaho, Ruffin Appalata, Yolande Yvonne Valeria Matoumona Mavoungou, Mbenza Ben Longo, Kenneth Ekoru, Blaise Makoso, Gedeon Longo Longo

Abstract:

Background: The gap between complexities related to the integration of Tuberculosis /HIV control and evidence-based knowledge motivated the initiation of the study. Therefore, the objective of this study was to explore correlations between national TB management guidelines, multiple deprivation indexes, quantiles, components and levels of Tuberculosis control programme using mathematical modeling in rural O.R. Tambo District Health Facilities, South Africa. Methods: The study design used mixed secondary data analysis and cross-sectional analysis between 2009 and 2013 across O.R Tambo District, Eastern Cape, South Africa using univariate/ bivariate analysis, linear multiple regression models, and multivariate discriminant analysis. Health inequalities indicators and component of an impediment to the tuberculosis control programme were evaluated. Results: In total, 62 400 records for TB notification were analyzed for the period 2009-2013. There was a significant but negative between Financial Year Expenditure (r= -0.894; P= 0.041) Seropositive HIV status(r= -0.979; P= 0.004), Population Density (r = -0.881; P= 0.048) and the number of TB defaulter in all TB cases. It was shown unsuccessful control of TB management program through correlations between numbers of new PTB smear positive, TB defaulter new smear-positive, TB failure all TB, Pulmonary Tuberculosis case finding index and deprivation-concentration-dispersion index. It was shown successful TB program control through significant and negative associations between declining numbers of death in co-infection of HIV and TB, TB deaths all TB and SMIAD gradient/ deprivation-concentration-dispersion index. The multivariate linear model was summarized by unadjusted r of 96%, adjusted R2 of 95 %, Standard Error of estimate of 0.110, R2 changed of 0.959 and significance for variance change for P=0.004 to explain the prediction of TB defaulter in all TB with equation y= 8.558-0.979 x number of HIV seropositive. After adjusting for confounding factors (PTB case finding the index, TB defaulter new smear-positive, TB death in all TB, TB defaulter all TB, and TB failure in all TB). The HIV and TB death, as well as new PTB smear positive, were identified as the most important, significant, and independent indicator to discriminate most deprived deprivation index far from other deprivation quintiles 2-5 using discriminant analysis. Conclusion: Elimination of poverty such as overcrowding, lack of sanitation and environment of highest burden of HIV might end the TB threat in O.R Tambo District, Eastern Cape, South Africa. Furthermore, ongoing adequate budget comprehensive, holistic and collaborative initiative towards Sustainable Developmental Goals (SDGs) is necessary for complete elimination of TB in poor O.R Tambo District.

Keywords: tuberculosis, HIV/AIDS, success, failure, control program, health inequalities, South Africa

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Authors: S. P. Chintan, A. M. Khoja, M. Modi, R. K. Chopra, S. Garde, D. Jain, O. Kajale

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Pulmonary Hypertension is a rare but debilitating disease that affects individuals of all ages and walks of life. As recent as 15 years ago, a patient diagnosed with PH was given an average survival rate of 2.8 years. Recent advances in treatment options have allowed patients to improve quality o and quantity of life. Initial screening for PH is through echocardiography with final diagnosis confirmed through right heart catheterization. PH is now considered to have five major classifications with subgroups among each. The mild to moderate PH is common in chronic lung diseases like Chronic obstructive pulmonary diseases and Interstitial lung disease. But very severe PH is noted in few cases. In COPD patients, PH is associated with an increased risk of severe exacerbations and a reduced life expectancy. Similarly, in patients with ILD, the presence of PH correlates with a poor prognosis. Early diagnosis is essential to slow disease progression. We report here five cases of severe PH (Out of Proportion) of which four cases were of COPD and another one of IPF (UIP pattern). There echocardiography showed gross RA/RV dilatation, interventricular septum bulging to the left and mPAP of more than 100 mmHg in all the five cases. These patients were put on LTOT, pulmonary rehabilitation, combination pharmacotherapy of vasodilators and diuretics in continuation to the treatment of underlying disease. As these patients have grave prognosis close monitoring and follow up is required. Physicians associated with respiratory care and treating chronic lung disease should have knowledge in the diagnosis and management of patients with PH.

Keywords: COPD, pulmonary hypertension, chronic lung disease, India

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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: A. Kherraf, M. Bouziane, A. Drighil, L. Azzouzi, R. Habbal

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Objective: Myxomas are rare heart tumors most commonly found in the left atrium. The purpose of this observation is to report a rare case of myxoma of the right atrium revealed by pulmonary embolism. Observation: A 34-year-old patient with no history presented to the emergency room with sudden onset dyspnea. Clinical examination showed arterial pressure at 110/70mmHg, tachycardia at 110bpm, and 90% oxygen saturation. The ECG enrolled in incomplete right bundle branch block. The radio-thorax was normal. Echocardiography revealed the presence of a large homogeneous intra-OD mass, contiguous to the inter-atrial septum, prolapsing through the tricuspid valve, and causing mild tricuspid insufficiency, with dilation of the right ventricle and retained systolic function with PAPs estimated at 45mmHg. A chest scan was performed, revealing the presence of right segmental pulmonary embolism. The patient was put under anticoagulant and underwent surgical resection of the mass; its pathological examination concluded to a myxoma. The post-operative consequences were simple, without recurrence of the mass after one year follow-up. Discussion: Myxomas represent 50% of heart tumors. Most often, they originate in the left atrium, and more rarely in the right atrium or the ventricles. Myxoma of the right atrium can be responsible for life-threatening pulmonary embolism. The most predictive factor for embolization remains the morphology of the myxomas; papillary or villous myxomas are the most friable. Surgery is the standard treatment, with regular postoperative follow-up to detect recurrence. Conclusion: Myxomas of the right atrium are a rare location for these tumors. Pulmonary embolism is the main complication and should routinely involve careful study of the right chambers on echocardiography.

Keywords: pulmonary embolism, myxoma, right atrium, heart tumors

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Authors: N. Naga Subrahmanyeswara Rao, Parag Arvind Deshpande

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Understanding nucleotide synthesis reaction of any organism is beneficial to know the growth of it as in Mycobacterium tuberculosis to design anti TB drug. One of the reactions of de novo pathway which takes place in all organisms was considered. The reaction takes places between phosphoribosyl pyrophosphate and orotate catalyzed by orotate phosphoribosyl transferase and divalent metal ion gives orotdine monophosphate, a nucleotide. All the reaction steps of three experimentally proposed mechanisms for this reaction were considered to develop kinetic rate expression. The model was validated using the data for four organisms. This model could successfully describe the kinetics for the reported data. The developed model can serve as a reliable model to describe the kinetics in new organisms without the need of mechanistic determination. So an organism-independent model was developed.

Keywords: mechanism, nucleotide, organism, tuberculosis

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Authors: Yun Wang, Ruoyu Wang, Tuo Chen, Guangxiu Liu, Guodong Chen, Wei Zhang

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Tuberculosis (TB) is a major public health problem in China. China has the world's second largest tuberculosis epidemic (after India). Xinjiang almost has the highest annual attendance rate of TB in China, and the province is also famous because of its severe dust storms. The epidemic timing starts in February and ends in July, and the dust storm mainly distribute throughout the spring and early summer, which strongly indicate a close linkage between causative agent of TB and dust storm events. However, mechanisms responsible for the observed patterns are still not clearly indentified. By comparing the information on cases of TB from Centers for Disease Control of China annual reports with dust storm atmosphere datasets, we constructed the relationship between the large scale annual occurrence of TB in Xinjiang, a Northwest province of China, and dust storm occurrence. Regional atmospheric indexes of dust storm based on surface wind speed show a clear link between population dynamics of the disease and the climate disaster: the onset of epidemics and the dust storm defined by the atmospheric index share the same mean year. This study is the first that provides a clear demonstration of connections that exist between TB epidemics and dust storm events in China. The development of this study will undoubtedly help early warning for tuberculosis epidemic onset in China and help nationwide and international public health institutions and policy makers to better control TB disease in Norwest China.

Keywords: dust storm, tuberculosis, Xinjiang province, epidemic

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Authors: A. Nusrath Unissa, Sameer Hassan, Luke Elizabeth Hanna

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Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.

Keywords: Mycobacterium tuberculosis, KatG, INH resistance, mutants, modelling, docking

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Authors: Kwok W. Mui, Ling T. Wong, Nai K. K. Fong

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Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in Hong Kong. Investigators are eager to explore the environmental risk factors for COPD such as air pollution and occupational exposure. Through a cross-sectional survey, this study investigates the impact of air quality to the quality of life of patients with the COPD in terms of the scores of the (Chinese) chronic respiratory questionnaire (CCRQ) and the measurements of indoor air quality (IAQ) and Moser’s activities of daily living (ADL). Strong relationships between a number of indoor/outdoor environmental parameters were found and CRQ sub-scores for patients of COPD and thus indoor air pollutants must be monitored for future studies related to QOL for patients with COPD.

Keywords: chronic obstructive pulmonary disease (COPD), indoor air pollutants, quality of life, chronic respiratory questionnaire (CRQ)

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Authors: Santony Santony, Teguh Rahayu Sartono, Iin Noor Chozin

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Introduction: Pneumonia is acute inflammation on lung parenchyma which is caused by bacteria, virus, fungi, or parasite. In Indonesia, Pneumonia is among the ten inpatient cases. Length of stay is related to the increased morbidity rate, nosocomial infection, and costs. The aim of this study is to assess the effect of pulmonary rehabilitation on the difference in length of stay and the level of Interleukin 6 (IL-6) as an inflammation biomarker for community-acquired pneumonia (CAP) patients in non-intensive rooms. Therefore, pulmonary rehabilitation as adjunctive therapy can be routinely exercised in order to shorten the length of stay, along with the decrease in IL-6 level. Methods: This study was conducted from May to October 2019 at Saiful Anwar General Hospital, Malang. 40 community-acquired pneumonia patients in non-intensive rooms were divided into two groups. 20 patients in the treatment group and 20 patients in the control group, all of them were selected through both inclusion and exclusion criteria. This study used simple consecutive random sampling. In the treatment group, pulmonary rehabilitation performed was composed of breathing exercise, effective coughing technique, clapping (percussion), postural drainage, as well as respiratory muscle training using incentive spirometry device. Pulmonary rehabilitation was conducted twice over five days with a minimum duration of 15 minutes. Blood samples were taken both on the first and the fifth day of the treatment to measure IL-6 level as an inflammation biomarker. Result: For the treatment group, the length of stay was 5.35 days whereas the control group 7.6 days. It can be seen that the treatment group had a shorter length of stay by 2.25 days (P<0,001). The IL-6 level on the first day for the treatment group was 36.27 pg/ml, whereas on the fifth day was 34.36 pg/ml. There was a decrease in IL-6 level on the fifth day of treatment even though it was not statistically significant (P=0.628). IL-6 level on the control group for the first day was 67.76 pg/ml, and after the fifth day, the level decreased to 54.43 pg/ml. There seemed to be a decrease in the IL-6, but it was not statistically significant (P=0.502). On the fifth day, the treatment group showed an average IL-6 level of 34.36 pg/ml. This value was lower than that of the control group which did not receive pulmonary rehabilitation having an IL-6 level of 54.43 pg/ml, even though it was not statistically significant (p=0.221). Conclusion: This study concluded that pulmonary rehabilitation as an adjunctive therapy shortened length of stay by 2.25 days for community-acquired pneumonia patients in a non-intensive room. Both groups experienced a decrease in IL-6 level on the fifth day in comparison with the first day even though it was not statistically significant P>0,05. IL-6 level as an inflammation biomarker decreased on the fifth day of treatment which was in accordance with improvement on pneumonia patients.

Keywords: community-acquired pneumonia, interleukin-6, length of stay, pulmonary rehabilitation

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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

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

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

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

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

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

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Authors: Gagan Dhawan

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

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

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Authors: Camilo Andres Agudelo-Velez, Lina María Martinez-Sanchez, Natalia Perilla-Hernandez, Maria De Los Angeles Rodriguez-Gazquez, Felipe Hernandez-Restrepo, Dayana Andrea Quintero-Moreno, Camilo Ruiz-Mejia, Isabel Cristina Ortiz-Trujillo, Monica Maria Zuluaga-Quintero

Abstract:

Chronic obstructive pulmonary disease is common condition, characterized by a persistent blockage of airflow, partially reversible and progressive, that represents 5% of total deaths around the world, and it is expected to become the third leading cause of death by 2030. Objective: To establish the clinical and epidemiological profile of patients with chronic obstructive pulmonary disease in a medical institution from the city of Medellin, Colombia. Methods: A cross-sectional study was performed, with a sample of 50 patients with a diagnosis of chronic obstructive pulmonary disease in a private institution in Medellin, during 2015. The software SPSS vr. 20 was used for the statistical analysis. For the quantitative variables, averages, standard deviations, and maximun and minimun values were calculated, while for ordinal and nominal qualitative variables, proportions were estimated. Results: The average age was 73.5±9.3 years, 52% of the patients were women, 50% of them had retired, 46% ere married and 80% lived in the city of Medellín. The mean time of diagnosis was 7.8±1.3 years and 100% of the patients were treated at the internal medicine service. The most common clinical features were: 36% were classified as class D for the disease, 34% had a FEV1 <30%, 88% had a history of smoking and 52% had oxygen therapy at home. Conclusion: It was found that class D was the most common, and the majority of the patients had a history of smoking, indicating the need to strengthen promotion and prevention strategies in this regard.

Keywords: pulmonary disease, chronic obstructive, pulmonary medicine, oxygen inhalation therapy

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

Abstract:

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

Keywords: Mycobacteria spp, raw milk, PCR, Zanjan

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

Abstract:

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

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

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

Abstract:

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

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

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Authors: Haji Ali Haji, Hussein Suleman, Ulrike Rivett

Abstract:

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

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

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

Abstract:

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

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

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Authors: Ghadeer M Alkusayer, Adelicia Yu, Pamela Orr

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Study objective: To report a case of postpartum pulmonary cryptococcal infection (CCI) in an otherwise healthy 35-year-old woman. Additionally, the cases of pulmonary cryptococcal infections either in the antepartum or the postpartum period with pregnancy outcomes, were systematically reviwed. Methods: A systematic search of Cochrane Library, MEDLINE, and EMBASE was conducted for peer-reviewed studies without date restrictions, published in English and relating to CCI during pregnancy or postpartum period. Conference press, editorials, opinion pieces and letters were excluded. Two authors independently screened citations and full-text articles, extracted data and assessed study quality. Given the heterogeneity of study designs, a narrative synthesis was conducted. Results: The search identified 128 references, of which 22 case reports and series met the inclusion criteria. This is a total of 29 women (including the current case) . The mean age of the women was 28.3 ± 12.3 years. Nine (31.03%) presented and were diagnosed in the postpartum period. Two (6.90%) of the patients were reported as immunocompromised with HIV. Four maternal deaths (13.79%) were found in this case series with one (4.3%) patient with severe neurological deficits. Four (17.4%) infant deaths were reported. Women primary presentation varied with chest pain 13 (44.82%), headache 10 (35.70%), dyspnea 19 (65.51%), or fever 12 (41.38%). Three studies reported placental pathology positive for C. neoformans. Conclusion: This case of pulmonary cryptococcal infection in the postpartum period is an important addition to the literature of this rare infection in pregnancy. The patient is not immunocompromised. The patient was successfully treated with 4 months of Fluconazole 400 mg and continued to breastfeed the healthy baby.

Keywords: pulmonary cryptococcus, pregnancy, cryptococci , postpartum

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

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

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

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Authors: Dipti Chand, Riya Saboo

Abstract:

OBJECTIVES: Early and correct diagnosis may present a significant clinical challenge in diagnosis of patients presenting to Emergency Department with Acute Dyspnoea. The common cause of acute dyspnoea and respiratory distress in Emergency Department are Decompensated Heart Failure (HF), Chronic Obstructive Pulmonary Disease (COPD), Asthma, Pneumonia, Acute Respiratory Distress Syndrome (ARDS), Pulmonary Embolism (PE), and other causes like anaemia. The aim of the study was to measure NT-pro Brain Natriuretic Peptide (BNP) and exhaled End-Tidal Carbon dioxide (ETCO2) in patients presenting with dyspnoea. MATERIAL AND METHODS: This prospective, cross-sectional and observational study was performed at the Government Medical College and Hospital, Nagpur, between October 2019 and October 2021 in patients admitted to the Medicine Intensive Care Unit. Three groups of patients were compared: (1) HFrelated acute dyspnoea group (n = 52), (2) pulmonary (COPD/PE)-related acute dyspnoea group (n = 31) and (3) sepsis with ARDS-related dyspnoea group (n = 13). All patients underwent initial clinical examination with a recording of initial vital parameters along with on-admission ETCO2 measurement, NT-proBNP testing, arterial blood gas analysis, lung ultrasound examination, 2D echocardiography, chest X-rays, and other relevant diagnostic laboratory testing. RESULTS: 96 patients were included in the study. Median NT-proBNP was found to be high for the Heart Failure group (11,480 pg/ml), followed by the sepsis group (780 pg/ml), and pulmonary group had an Nt ProBNP of 231 pg/ml. The mean ETCO2 value was maximum in the pulmonary group (48.610 mmHg) followed by Heart Failure (31.51 mmHg) and the sepsis group (19.46 mmHg). The results were found to be statistically significant (P < 0.05). CONCLUSION: NT-proBNP has high diagnostic accuracy in differentiating acute HF-related dyspnoea from pulmonary (COPD and ARDS)-related acute dyspnoea. The higher levels of ETCO2 help in diagnosing patients with COPD.

Keywords: NT PRO BNP, ETCO2, dyspnoea, lung USG

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

Abstract:

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

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

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Authors: Domingos Vita, Patrick Brady

Abstract:

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

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

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

Abstract:

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

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

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