From pulmonary susceptible tuberculosis to extensively drug resistant tuberculosis: An interesting case report of a young Indian girl.

Tuberculosis is one of the top ten causes of death and the leading cause from a single infectious agent. Drug-resistant Tuberculosis continues to be a public health crisis. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people with drug-resistant Tuberculosis. Patients with pulmonary Tuberculosis can spread the disease by coughing, sneezing, or simply talking. For that reason, it is important to diagnosis Tuberculosis in order to start treatment as soon as possible. In the present manuscript we present the case of a 25-year-old Indian HIV-negative female, no comorbidity, with a history of drug susceptible tuberculosis diagnosed in 2015 which advanced in extensively drug-resistant tuberculosis after two years of treatment. This case report highlights the risk of mismanagement of patient affected by Tuberculosis and the consequences related which could harm the patient's health.

TB sequel: incidence, pathogenesis and risk factors of long-term medical and social sequelae of pulmonary TB - a study protocol

Background: Up to fifty percent of microbiologically cured tuberculosis (TB) patients may be left with permanent, moderate or severe pulmonary function impairment. Very few studies have systematically examined pulmonary outcomes in patients to understand the pathophysiologic basis and long-term socio-economic consequences of this injury. The planned multi-country, multi-centre observational TB cohort study, aims to advance the understanding of the clinical, microbiological, immunological and socio-economic risk factors affecting long-term outcome of pulmonary TB. It will also determine the occurrence of reversible and irreversible socio-economic consequences to patients, their households and the health sector related to pulmonary TB disease and its treatment

Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment.

In 2013, 86% of patients with newly diagnosed tuberculosis (TB) successfully completed treatment and were discharged from care. However, long-term studies in industrialised and resource-poor countries all point to a higher risk of death in TB survivors than in the general population. The likely explanation is chronic restrictive and obstructive lung disease consequent to TB. We call for better linkages between TB control programmes and respiratory medicine services, a better understanding of the burden of respiratory disability at the end of anti-tuberculosis treatment, and political, programmatic, clinical and research action to improve the quality of life of affected patients.

Significance of nutrition in pulmonary tuberculosis.

Malnutrition and tuberculosis are both problems mostly of the developing countries. Tuberculosis can lead to malnutrition and malnutrition may predispose to tuberculosis. Poor nutrition leads to protein-energy malnutrition and micronutrients deficiencies which lead to immunodeficiency. This secondary immunodeficiency increases the host's susceptibility to infection and hence increase the risk for developing tuberculosis. Tuberculosis itself leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting and poor nutritional status. Nutritional status and dietary intake and hence nutritional status of patients get improved during antituberculosis treatment.

Papel de la vitamina D en enfermedad pulmonar obstructiva crónica, asma y otras enfermedades respiratorias / The Role of Vitamin D in Chronic Obstructive Pulmonary Disease, Asthma and Other Respiratory Diseases

En los últimos años existe un creciente interés por las acciones extraóseas de la vitamina D. En este artículo revisamos la fisiología de la vitamina D, los aspectos fisiopatológicos asociados a su déficit y la evidencia existente sobre su papel etiopatogénico en enfermedades respiratorias. Teniendo en cuenta las acciones pleiotrópicas de la vitamina D, existe plausibilidad biológica sobre un potencial papel patogénico del déficit de esta vitamina en el desarrollo de diversas enfermedades respiratorias. Sin embargo, los numerosos estudios epidemiológicos que han encontrado asociación entre niveles bajos de vitamina D y mayor riesgo de desarrollar diversas enfermedades respiratorias o de conllevar un peor pronóstico no permiten demostrar causalidad. Los análisis post hoc de algunos ensayos clínicos, especialmente en enfermedad pulmonar obstructiva crónica (EPOC) y asma, parecen demostrar que ciertos subtipos de pacientes podrían beneficiarse de la corrección del déficit de vitamina D. En este sentido, resultará interesante averiguar si las variantes genéticas implicadas en el metabolismo de la vitamina D pueden explicar las diferencias interindividuales encontradas en cuanto al efecto del déficit de vitamina D y la respuesta a su corrección. En último término, solo los ensayos clínicos adecuadamente diseñados permitirán determinar si los suplementos de 25-OH D pueden tener un efecto preventivo o mejorar la evolución de las distintas enfermedades respiratorias en las que se ha descrito asociación epidemiológica entre su pronóstico y el déficit de esta vitamina

There has been a growing interest in recent years in the extraosseous effects of vitamin D. In this article, we review the physiology of vitamin D, the physiopathological effects associated with vitamin D deficit and the available evidence on its etiopathogenic role in respiratory diseases. Given the pleiotropic actions of vitamin D, it is biologically plausible that the deficit of this vitamin could play a pathogenic role in the development of various respiratory diseases. However, the many epidemiological studies that have shown an association between low vitamin D levels and a higher risk of developing various respiratory diseases, or a poorer prognosis if they do appear, were unable to show causality. Post hoc analyses of some clinical trials, particularly in chronic obstructive pulmonary disease (COPD) and asthma, appear to suggest that some patient subtypes may benefit from correction of a vitamin D deficit. In this respect, it would be interesting to determine if the interindividual differences found in the effect of vitamin D deficit and responses to correcting this deficit could be explained by the genetic variants involved in vitamin D metabolism. Ultimately, only appropriately designed clinical trials will determine whether 25-OH D supplements can prevent or improve the course of the various respiratory diseases in which an epidemiological association between prognosis and vitamin D deficit has been described

Assessment of health-related quality of life in patients with pulmonary tuberculosis under programme conditions.

SETTING: Newly diagnosed pulmonary tuberculosis (PTB) patients starting treatment under the Revised National Tuberculosis Control Programme (RNTCP) in a North Indian city. OBJECTIVE: To quantify impairment in health-related quality of life (HRQoL) of PTB patients at the time of diagnosis and during treatment, and to assess the utility of these assessments as a measure of outcome under programme conditions. DESIGN: HRQoL was assessed using the Hindi version of the 26-item World Health Organization Quality of Life (WHOQOL-BREF) scale at the start and end of the intensive phase and at completion of treatment. Four domain scores-physical, psychological, social relationships and environment-were calculated and compared between groups, based on different patient and disease characteristics. Psychometric evaluation was conducted by assessing acceptability, validity and responsiveness of the questionnaire. RESULTS: A total of 2654 HRQoL assessments were performed among 1034 patients. Domain scores were generally better among men, urban residents, younger patients, patients with higher socio-economic status and those with less severe disease. The WHOQOL-BREF demonstrated good psychometric properties, and domain scores improved with treatment. Residual HRQoL impairment was noted in some patients even at treatment completion. CONCLUSION: HRQoL is impaired in patients with PTB, and improves rapidly and significantly with programme-based treatment. HRQoL assessment can be used as an adjunct outcome measure for patients treated by the RNTCP.

The effect of energy-protein supplementation on weight, body composition and handgrip strength among pulmonary tuberculosis HIV-co-infected patients: randomised controlled trial in Mwanza, Tanzania.

Undernutrition is common among smear-positive pulmonary tuberculosis (PTB+) patients. Micronutrient supplementation may improve treatment outcomes, but it is unclear whether additional energy-protein would be beneficial. The present study aimed to assess the effect of energy-protein supplementation on weight, body composition and handgrip strength against a background of high micronutrient intake during tuberculosis (TB) treatment. A total of 377 PTB+ patients co-infected with HIV were randomly allocated one or six biscuits daily for 60 d during TB treatment. Weight, arm fat area, arm muscle area and handgrip strength were assessed at baseline and 2 and 5 months. There were no effects on any outcome at 2 months, but energy-protein supplementation was associated with a 1·3 (95 % CI - 0·1, 2·8) kg marginally significant gain in handgrip strength at 5 months. However, after 2 months, energy-protein supplementation led to a weight gain of 1·9 (95 % CI 0·1, 3·7) kg among patients with cluster of differentiation 4 (CD4) counts ≥ 350 cells/µl, but not among patients with low CD4 counts ( - 0·2 kg; 95 % CI - 1·3, 0·8, Pinteraction = 0·03). Similarly, at 5 months, energy-protein supplementation led to a 2·3 (95 % CI 0·6, 4·1) kg higher handgrip strength gain among patients with CD4 counts < 350 cells/µl, but not in those with high CD4 counts (Pinteraction = 0·04). In conclusion, energy-protein supplementation to PTB+ HIV-co-infected patients had no overall effects on weight and body composition, but was associated with marginally significant gain in handgrip strength. More research is needed to develop an effective supplement, before it is recommended to TB programmes.

Anemia and pregnancy: a link to maternal chronic diseases.

Anemia is a global public health problem. It has serious short- and long-term consequences during pregnancy and beyond. The anemic condition is often worsened by the presence of other chronic diseases such as malaria, tuberculosis, HIV, and diabetes. Untreated anemia also leads to increased morbidity and mortality from these chronic conditions as well. It is surprising that despite these chronic conditions (such as malaria, tuberculosis, and HIV) often being preventable, they still pose a real threat to public health. This article aims to review the current understanding of the pathophysiology, risks, prevention, and treatment of anemia in the light of these chronic conditions.

Catheter ablation of atrial fibrillation in patients with chronic lung disease.

BACKGROUND: Chronic lung disease (CLD) is one of the important underlying diseases of atrial fibrillation (AF). The outcomes after radiofrequency catheter ablation of AF in patients with CLD have not yet been reported. We investigated the electroanatomic alterations in pulmonary veins (PVs) in CLD patients with AF and assessed their effect on the outcomes of radiofrequency catheter ablation of AF. METHOD AND RESULTS: We assessed 15 patients who had CLD and underwent radiofrequency catheter ablation of AF. CLD included chronic obstructive pulmonary disease, a tuberculosis-destroyed lung, and interstitial lung disease. For controls, we selected 60 sex-, age-, and procedure era-matched non-CLD patients who received radiofrequency catheter ablation for AF (4 controls for each CLD patient). Eight patients had chronic obstructive pulmonary disease, 6 had a tuberculosis-destroyed lung, and 1 had interstitial lung disease. PV morphology in the affected lung was altered significantly, ie, obliteration, pulling of the PVs toward the destroyed lung, or compensatory bulging of the PV antrum. These alterations were related to arrhythmogenicity in 6 (40%) of 15 patients with CLD. Non-PV foci were more common in the CLD group (4/15, 26.7%) than in the control group (3/60, 5.0%; P=0.025). All non-PV foci were located in the right atrium. The AF recurrence rate in the CLD group (26.7%, 4/15) was similar to that in the control group (18.3%, 11/60; P=0.45). CONCLUSIONS: Significant alteration of PV anatomy was related to arrhythmogenicity, and non-PV foci from the right atrium were commonly observed in the CLD group. Radiofrequency catheter ablation can be performed safely for AF in CLD patients with a comparable success rate to that in patients with normal lungs.

The Yin-Yang of TNFalpha in the guinea pig model of tuberculosis.

Tumour necrosis factor alpha (TNF-alpha) is a prototypic pro-inflammatory cytokine that has a central role in the initial host response to Mycobacterium tuberculosis infection. It is a key player in granuloma formation, macrophage activation, bacterial killing, and pathology in vivo. However, the exact mechanism has not been completely understood. This review summarizes the TNFalpha data acquired from the 'gold standard' guinea pig animal model of tuberculosis. While production of TNFalpha is widely accepted as beneficial to the host response, we have found that this hypothesis is just one side of the story. TNFalpha can up-regulate and down-regulate some key pro-inflammatory cytokines (IFNgamma, IL-12p40) and differentially modulate macrophage activation and intracellular bacterial growth. Neutralization of TNFalpha in vivo allows an antiinflammatory TGFbeta-mediated response to develop. Furthermore, BCG vaccination modulates TNFalpha responses directly in the pulmonary granulomas to reduce tissue damage. The bipolar nature of TNFalpha should be considered as knowledge of this critical molecule continues to grow.

Enhancement of efficacy of tuberculosis drugs with Immunoxel (Dzherelo) in HIV-infected patients with active pulmonary tuberculosis.

Immunoxel (Dzherelo) is an oral, herbal immunomodulator used in Ukraine for adjunct therapy of infectious and autoimmune diseases. Antiretroviral drug-naive, tuberculosis (TB)/HIV coinfected patients with active pulmonary TB were divided into two arms, A (n = 20) and B (n = 20), to receive first-line anti-TB therapy (ATT) or ATT + Dzherelo, respectively. As a result, three (16%) versus 12 (67%; p = 0.003) patients had Mycobacterium tuberculosis culture conversion, with time to negative culture of 6 and 4 months in arms A and B, respectively. In the ATT-alone arm, the healing of pulmonary cavitations was observed in 25% of patients at weeks 24-28, while 60% of individuals in arm B healed at 16-18 weeks (p = 0.025). The TB lesions, on chest x-ray, had cleared in 46 and 84%, with time-to-clearance of 24-28 and 16-18 weeks in arms A and B, respectively. In the ATT-alone arm, the bodyweight at baseline was 64 +/- 6.3 kg, with 13 cachexic patients who had an average weight deficit of -5.2 +/- 1.7 kg. At the end of 6 months of follow-up, they have lost an additional 0.6 kg (-5.8 +/- 2.4). The study entry-level weight in arm B was 52 +/- 5.7 kg, with 12 individuals who had a body mass deficit of -8.5 +/- 2.7 kg. The immunotherapeutic intervention increased bodyweight by an average of 5.8 +/- 2.6 kg above baseline (p < 0.0001). The inclusion of Dzherelo into the ATT regimen decreased the incidence of new opportunistic infections (OI) with three episodes of OI versus 12 in arm A (p = 0.003). These findings indicate that Dzherelo contributes positively to the clinical efficacy of TB drugs.

The road to tuberculosis treatment in rural Nepal: A qualitative assessment of 26 journeys.

BACKGROUND: The fact that tuberculosis can be treated with the DOTS strategy (Directly Observed Treatment, Short-course) is not enough to control the disease. Patients have to find their way to tuberculosis treatment first. To better understand the route to tuberculosis treatment in rural Nepal we interviewed twenty-six patients under treatment. METHODS: In semi-structured interviews patients shared their disease history and health seeking behaviour. The analysis focused on the encounters with the health care system before enrolment in the tuberculosis treatment program. RESULTS: Patient routes often started in the medical shop and led via intricate routes with multiple providers to facilities with higher qualified and more competent staff where tuberculosis was diagnosed. Several factors influenced the route to tuberculosis treatment. Besides known patients factors (such as severity of complaints, the ability to pay for services, availability of services and peer support for choosing a provider) specific health services factors were also identified. These included the perceived quality, costs and service level of a provider, and lack of provider initiated referral. Self referral because of waned trust in the provider was very common. In contrast, once tuberculosis was considered a possible diagnosis, referral to diagnostic testing and tuberculosis treatment was prompt. CONCLUSION: Patient routes towards tuberculosis treatment are characterised by self referral and include both private and public health care providers. Once tuberculosis is suspected referral for diagnosis and treatment is prompt. Given the importance of the private practitioners in the patient routes, quality improvement initiatives need to address not only the public sector but the private health care sector as well.

Respiratory muscle training in restrictive thoracic disease: a randomized controlled trial.

OBJECTIVE: To investigate the effects of respiratory muscle training (RMT) in patients with restrictive thoracic disorders and intermittent noninvasive positive-pressure ventilation (NPPV). DESIGN: Prospective randomized controlled trial. SETTING: Home-based RMT, with assessment in a primary care pulmonary center. PARTICIPANTS: Thirty patients with restrictive thoracic disorders; 28 patients completed the trial. INTERVENTION: Three months of RMT by isocapnic hyperpnea or sham training. MAIN OUTCOME MEASURES: Respiratory muscle strength and endurance, lung function, exercise performance, and health-related quality of life (HRQOL). RESULTS: After RMT, maximal inspiratory mouth pressure was increased (27.6%+/-36.5%, P=.013). In patients who could perform cycle ergometer testing (n=17), peak oxygen consumption (2.24+/-3.39mLxkg(-1).min(-1) vs -1.71+/-2.54mLxkg(-1).min(-1), P=.014) and maximal work rate (9.4+/-14.8W vs -5.1+/-10.8W, P=.043) increased relative to a control group. Similar differences occurred regarding changes of HRQOL (physical performance, 3.3+/-11.4 score vs -6.6+/-9.0 score; P=.012) and time of ventilator use (-0.6+/-1.2h/d vs 0.4+/-0.5h/d, P=.010). Lung volumes, 12-second maximum voluntary ventilation, 6-minute walking distance, and blood gases were unchanged. CONCLUSIONS: In patients with restrictive thoracic disorders and NPPV, RMT improved inspiratory muscle strength. Exercise performance and HRQOL were improved when the 2 groups were compared. RMT was practicable and safe despite severe respiratory impairment. Further evaluation, including different training intensities and modalities, seems warranted.

[Use of alpha-tocopherol acetate in the treatment of hemodynamic disorders in patients with pulmonary tuberculosis].

Examination of 101 patients with pulmonary tuberculosis established the impact of specific intoxication on central hemodynamics in 51 patients. Specific treatment was found to have a certain positive effect on impaired hemodynamics. However, there were no significant changes in patients with severe tuberculosis. Hemodynamics substantially improved when alpha-tocopherol acetate was supplemented to antibacterial therapy.

The endocrinology of adrenal tuberculosis: the effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function.

Tuberculosis may affect many of the endocrine glands including the hypothalamus, pituitary, thyroid and adrenals. The most commonly involved endocrine organ in tuberculosis is the adrenal gland. Adrenal glands may be directly or indirectly affected by tuberculosis. Tuberculous Addison's disease is still an important cause of primary adrenocortical insufficiency particularly in the developing countries. Recent improvements in imaging techniques and modern endocrinological tests for the investigation of adrenal function have given us greater insight into the endocrinology of adrenal tuberculosis. Hypothalamo-pituitary-adrenal (HPA) axis is also involved in tuberculosis and recent findings revealed that HPA axis is activated rather than underactivated in active pulmonary tuberculosis. Activated HPA axis in tuberculosis causes increased cortisol secretion which results in a shift in the Th1/Th2 balance towards Th2. T cell dysfunction due to high cortisol and low DHEAS levels may be responsible for immunologically-mediated tissue damage in tuberculosis. In this review, recent findings concerning the adrenocortical function, radiological changes in adrenal glands and HPA axis involvement in tuberculosis are discussed.

Randomized trial of yoga as a complementary therapy for pulmonary tuberculosis.

OBJECTIVE: The present prospective, randomized trial compared the efficacy of anti-tuberculosis treatment (ATT) with two separate programs (yoga and breath awareness), on lung capacities and bacteriological status in pulmonary tuberculosis patients. METHODOLOGY: A total of 1009 pulmonary tuberculosis patients were screened and 73 were alternately allocated, to yoga (n = 36) or breath awareness (n = 37) groups, with 48 patients completing the 2-month trial. Patients aged between 20 and 55 years, who were sputum-positive on three consecutive examinations, had no prior ATT, and no comorbidities or extrapulmonary tuberculosis were included. In addition to ATT, one group practised yoga (n = 25) and the other practised breath awareness (n = 23) for 6 h per week, each session being 60 min. The main outcome measures were: symptom scores, bodyweight, FVC, FEV(1), FEV(1)/FVC%, sputum microscopy, sputum culture, and postero-anterior view of the CXR. RESULTS: At the end of 2 months, the yoga group showed a significant reduction in symptom scores (88.1%), and an increase in weight (10.9%), FVC (64.7%) and FEV(1) (83.6%) (P = 0.001, in all comparisons, paired t-test). The breath awareness group also showed a significant (paired t-test) reduction in symptom scores (16.3%, P= 0.02), and an increase in weight (2.1%, P= 0.003) and FEV(1) (63.8%, P= 0.04). Significantly more patients in the yoga group showed sputum conversion based on microscopy on days 30 and 45 compared to the breath awareness group (P = 0.045 and P= 0.002, respectively, chi(2) test). Ten of 13 in the yoga group had negative sputum culture after 60 days compared with four of 19 in the breath awareness group (P = 0.005, chi(2) test). Improvement in the radiographic picture occurred in 16/25 in the yoga group compared to 3/22 in the breath awareness group on day 60 (P = 0.001, chi(2) test). CONCLUSIONS: The improved level of infection, radiographic picture, FVC, weight gain and reduced symptoms in the yoga group suggest a complementary role for yoga in the management of pulmonary tuberculosis.

[Evaluation of the efficacy of a plant adaptogen (spirulina) in the pathognic therapy of primary tuberculosis in children]. / Otsenka efektyvnosti zastosuvannia adaptohenu roslynnoho pokhodzhennia (spiruliny) u patohenetychnii terapii pervinnoho tuberkul'ozu y direi.

The use of spirulina and its efficiency have been studied in a comparative aspect as a systemic biocorrector, in a combined treatment of tuberculosis in 26 children. It has been ascertained that application of spirulina as a pathogenetic means of remediation permits shortening the intoxication syndrome regression time, reducing the frequency of adverse reactions in administering antituberculous preparations.

Low dose (1 microg) adrenocorticotropin stimulation test in the evaluation of hypothalamo-pituitary-adrenal axis in patients with active pulmonary tuberculosis.

Adrenocortical function in patients with active pulmonary tuberculosis is a debate of matter. Previous studies related to adrenocortical function in patients with active pulmonary tuberculosis demonstrated a high rate of suboptimal cortisol response to standard dose ACTH (250 microg) stimulation test. The aim of this study was to assess the hypothalamo-pituitary-adrenal (HPA) axis in low dose (1 microg) and standard dose ACTH (250 microg) stimulation tests in the patients with active pulmonary tuberculosis. Twenty-seven patients and 21 healthy subjects were included in the study. Cortisol levels were measured before, 30 and 60 min after ACTH (1 microg or 250 microg iv) injection. Cortisol responses to 1 microg ACTH at 30 and 60 min were significantly higher in the patient group than in the control group (p<0.05). Peak cortisol levels were significantly higher in the patient group than in the control group after both 1 microg and 250 microg ACTH administration (p<0.05). Cortisol responses to 250 microg ACTH at 30 and (at 30 and 60) 60 min were significantly higher in the patient group than in the control group (p<0.05). Peak cortisol levels obtained after 250 microg ACTH and after 1 microg ACTH were similar in the patient group (p>0.05). This study shows that 1 microg ACTH iv gives an equivalent peak cortisol value to 250 microg ACTH in patients with activated HPA axis. The cortisol levels obtained at 08:00, 11:00, 17:00 and 24:00 h were significantly higher in the patients than in the controls. This study clearly shows that HPA axis is activated in active pulmonary tuberculosis rather than underactivated.