Availability of drugs and resistance testing for BPaLM regimen for rifampicin-resistant tuberculosis in Europe.

OBJECTIVES: Multidrug-resistant/Rifampicin-resistant tuberculosis (TB) is a major obstacle to successful TB control. The recommendation by the World Health Organization to use bedaquiline, pretomanid, linezolid and moxifloxacin (BPaL(M)) for 6 months, based on results of three trials with high efficacy and low toxicity, has revolutionized treatment options. METHODS: In this study, representatives of the Tuberculosis Network European Trialsgroup (TBnet) in 44/54 countries of the WHO Europe region document the availability of the medicines and drug susceptibility testing (DST) of the BPaL(M) regimen through a structured questionnaire between September to November 2023. RESULTS: 24/44 (54.5%), 42/44 (95.5%), 43/44 (97.7%), and 43/44 (97.7%) had access to pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, 23/44 (52.3%) had access to all the drugs composing the BPaL(M) regimen. 7/44 (15.9%), 28/44 (63.6%), 34/44 (77.3%) and 36/44 (81.8%) had access to DST for pretomanid, bedaquiline, linezolid and moxifloxacin, respectively. DST was available for all medicines composing the BPaL(M) regimen in 6/44 (13.6%) countries. CONCLUSION: Only in about half of the countries participating in the survey clinicians have access to all the BPaL(M) regimen drugs. In less than a fifth of countries, a complete DST is possible. Rapid scale up of DST capacity to prevent unnoticed spread of drug resistance and equal access to new regimens are urgently needed in Europe.

Influence of the COVID-19 pandemic on the incidence of tuberculosis and influenza.

We examined whether the COVID-19 pandemic has affected the incidence of tuberculosis (TB) and influenza in Serbia, a Southeast European country with a low TB incidence rate and a mandatory BCG vaccination at birth. The first case of COVID-19 was registered on March 6, 2020. Despite the need for a sudden adaptation of the health care system, routines of mycobacterial laboratories have never stopped. In 2020, the number of newly diagnosed TB patients was significantly lower than expected (p = 0.04), but the number of patients with influenza increased when compared to 2019. Although many patients with influenza A H1N1 were observed before the beginning of the COVID-19 pandemic, the increment of cases could also be a consequence of cases of influenza with COVID-like symptoms detected thereafter. It may also be attributed to misclassification of clinical cases that were negative for SARS-CoV-2 and reported as influenza. Difficulties to seek medical attention because of the COVID-19 pandemic and possible underreporting are considered as reasons for the decline in the incidence rate of TB. On the other hand, individual and social measures to prevent the spread of SARS-CoV-2 such as wearing face masks, social distancing, lockdown, which were strictly applied to COVID-19 patients, health care staffs and most of the population, could have hindered TB infections more than the two viral diseases, which appear to be more contagious. The increased motivation of the population to protect their health during the COVID-19 pandemic provided an opportunity for their effective education. This is crucial in further combating TB as a preventable disease.

Improving the evidence for indicator condition guided HIV testing in Europe: Results from the HIDES II Study - 2012 - 2015.

BACKGROUND: It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. METHODS: Individuals aged 18-65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. RESULTS: Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5-3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. CONCLUSION: The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.

Prevalence of diabetes mellitus (DM) in tuberculosis (TB) patients: clinical and radiologic features in the TB-DM association based on a five-year hospital study.

A previously known association of tuberculosis (TB), now a global emergency, with diabetes mellitus (DM), a chronic disease of increasing prevalence worldwide, has resurfaced. DM is a recognised TB risk factor and M. tuberculosis infection usually disturbs glycoregulation. We aimed to estimate DM prevalence among TB patients and to analyse clinical and radiologic manifestations of TB in this group. The cross-sectional study included 1017 patients discharged with a TB diagnosis from a tertiary level facility in a five-year period. After exclusion of 128 patients with TB sequelae, we selected 889 patients with confirmed active TB, and the final selection led to 88 subjects with both active TB and DM. DM was found in 9.89% of active TB patients. Testing hypotheses for single-sample proportions showed that the prevalence was significantly higher than the prevalence in the general population (p<0.01). The average patient age was 60.47±14.88 years (range: 20-88), while the male/female ratio was 2.26. We found pulmonary TB in 96.3% of the 88 subjects, and extrapulmonary in 3.4%, the latter more frequently in women (p=0.08). Cavities were more frequently found in tobacco smokers compared to non-smokers (p=0.002) and in patients living in rural settings (p=0.002); haemoptysis was detected more frequently in men compared to women (p=0.044). Half of the patients had no fever at all, and only 14.8% had tachycardia. Auscultatory findings were positive in 57 (64.8%) patients. Radiographic changes were atypical in 17/88 (19.3%) patients and included pulmonary bases in seven patients, upper lobe anterior segment, and disseminated miliary pattern in two patients. DM prevalence is significantly higher among TB patients compared to the general population. The mean age of TB patients with DM is significantly higher than expected in TB patients alone. Knowledge of TB clinical and radiologic variations in this group of patients may reduce the delay in TB diagnosis with its clinical and epidemiologic consequences.

First reported case of fulminant TB with progression of infection from lungs to the genitourinary region.

Although tuberculosis (TB) is a curable disease, it continues to be one of the leading infections associated with death in the world. Extra-pulmonary TB (EPTB) occurs in approximately 10% of the total cases, presenting with lymph nodes, pleura, bone and genitourinary tract as the most common locations. Genitourinary tuberculosis, the second most common EPTB, is very difficult to diagnose unless there is a high index of suspicion. Isolated TB orchitis or prostatitis without clinical evidence of renal involvement is a rare entity among genitourinary tuberculosis. We presented the first reported case of TB prostatitis and orchitis associated with pulmonary TB and the presence of an acute massive caseous pneumonia in an immunocompetent man. Despite the anti-TB therapy, the patient presented a rapid progression of disease and deterioration of general conditions taking to death, which occurred four days after TB treatment had started. Disseminated TB is a relatively uncommon cause of acute massive caseous pneumonia; however, there should always be suspicion of the disease, since it is a potentially treatable cause. This rare case supports the assertion that TB should be considered as an important differential diagnosis of genitourinary tumors irrespective of evidence of active TB elsewhere in the body.

First reported case of fulminant TB with progression of infection from lungs to the genitourinary region

ABSTRACT Although tuberculosis (TB) is a curable disease, it continues to be one of the leading infections associated with death in the world. Extra-pulmonary TB (EPTB) occurs in approximately 10% of the total cases, presenting with lymph nodes, pleura, bone and genitourinary tract as the most common locations. Genitourinary tuberculosis, the second most common EPTB, is very difficult to diagnose unless there is a high index of suspicion. Isolated TB orchitis or prostatitis without clinical evidence of renal involvement is a rare entity among genitourinary tuberculosis. We presented the first reported case of TB prostatitis and orchitis associated with pulmonary TB and the presence of an acute massive caseous pneumonia in an immunocompetent man. Despite the anti-TB therapy, the patient presented a rapid progression of disease and deterioration of general conditions taking to death, which occurred four days after TB treatment had started. Disseminated TB is a relatively uncommon cause of acute massive caseous pneumonia; however, there should always be suspicion of the disease, since it is a potentially treatable cause. This rare case supports the assertion that TB should be considered as an important differential diagnosis of genitourinary tumors irrespective of evidence of active TB elsewhere in the body.

Pulmonary and Vertebral Mycobacterium avium Disease in a HIV-negative 71-year-old Man - A Case Report.

Nontuberculous mycobacteria (NTM) caused pulmonary disease is on increase worldwide, especially in countries with decreasing time trend of tuberculosis incidence. NTM skeletal affection is rare. Mycobacterium avium related disease, with still unclear clinical and radiologic features, is in current focus of both clinicians and researchers. An exhausted severely ill 71-year-old man was admitted on emergency due to cough, dyspnea and lumbar back pain to be diagnosed with terminal phase M. avium disease. Three sputum smears were positive for acid fast bacilli and M. avium was identified with hybridization reaction by means of GenoType ® MTBC (Hain). Apart from pulmonary disease, compressive fractures of the 12th thoracic and 1-4th lumbar vertebrae were detected. We found age, chronic alcoholism, previous professional exposure, tobacco smoking, chronic obstructive pulmonary disease and previous tuberculosis as risk factors for NTM disease in the HIV-negative patient. Despite combined antibiotic treatment, disease had lethal outcome. This case report might contribute to clinicians' awareness and improved knowledge on this sort of pathology, and lead to earlier diagnosis with possibly better disease outcome.

Pregnancy in patients with tuberculosis: a TBNET cross-sectional survey.

BACKGROUND: Objectives: To determine whether the incidence of tuberculosis with pregnancy is more common than would be expected from the crude birth rate; to see whether there is significant delay in the diagnosis of tuberculosis during pregnancy. METHOD: Design: A cross-sectional survey. SETTING: 13 tuberculosis clinics within different European countries and the USA. POPULATION/SAMPLE: All patients with tuberculosis seen at these clinics for a period > 1 year. INSTRUMENT: Questionnaire survey based on continuous data collection. MAIN OUTCOME MEASURES: number and proportion of women with tuberculosis who were pregnant; timing of diagnosis in relation to pregnancy, including those who were pregnant or delivered in the 3 months prior to the diagnosis of TB and those who developed TB within 3 months after delivery. RESULTS: Pregnancy occurred in 224 (1.5 %) of 15,217 TB patients and followed the expected rate predicted from the crude birth rate for the clinic populations. TB was diagnosed more commonly in the 3 months after delivery (n = 103) than during pregnancy (n = 68; χ 2 = 25.1, P < 0.001). CONCLUSIONS: TB is diagnosed more frequently after delivery, despite variations in local TB incidence and healthcare systems.

Synchronous advanced pulmonary tuberculosis and acute virus myocarditis mimicked Wegener granulomatosis in a 26-year-old man ­ A case report.

Introduction: Tuberculosis patients are rarely asymptomatic. Acute virus myocarditis presents with a wide range of symptoms, from mild dyspnea or chest pain to cardiogenic shock and death. Case Outline: A 26-year-old Caucasian man non-smoker presented with one-week history of lower extremities' swelling. The patient's medical history also revealed a two-day episode of subfebrile temperature with scanty hemoptysis three weeks prior to admission. The episode had not provoked him to seek medical care. Physical examination revealed generalized oedema, and laboratory analysis showed signs of acute renal insufficiency. Enlarged heart and hilar shadows, bilateral massive cavitary pulmonary opacities and pleural effusion were found at chest radiography. Sputum smears were Mycobacteria negative on direct microscopy. Electrocardiogram changes and echocardiography were suggestive of acute myocarditis with dilated cardiomyopathy. IgM titer to adenovirus was positive. Under diuretics, angiotensin-converting-enzyme inhibitor, beta-blocker, antibiotics and bed rest, fast heart compensation and renal function repair were achieved. Radiographic pulmonary changes promptly regressed except for a cavity in the right upper lobe. Bronchial aspirate from the affected lobe was Mycobacteria positive on direct microscopy and culture positive for Mycobacterium tuberculosis. Standard anti-tuberculosis drug regimen led to recovery. Conclusion: In the unusual common existence of two diseases whose presentation initially mimicked Wegener's granulomatosis, acute dilated cardiomyopathy contributed to pulmonary tuberculosis detection. To prevent diagnostic delay in tuberculosis, further efforts in population education are necessary together with continual medical education

Bullous lung diseases as a risk factor for lung cancer: A case report.

Introduction: A possible association between lung cancer and bullous lung disease has been suggested and recently supported by the results of genetic studies. Case report: A previously healthy 43-year-old man, smoker, was diagnosed with bullous lung disease at the age of 31 years. He was followed up for 12 years when lung cancer (adenocarcinoma) was found at the site. In the meantime, he was treated for recurrent respiratory infections. Conclusion: There is the need for active approach in following up the patients with pulmonary bulla for potential development of lung cancer.

Drug induced lung disease--amiodarone in focus.

More than 380 medications are known to cause pulmonary toxicity. Selected drugs that are important causes of pulmonary toxicity fall into the following classes: cytotoxic, cardiovascular, anti-inflammatory, antimicrobial, illicit drugs, miscellaneous. The adverse reactions can involve the pulmonary parenchyma, pleura, the airways, pulmonary vascular system, and mediastinum. Drug-induced lung diseases have no pathognomonic clinical, laboratory, physical, radiographic or histological findings. A drug-induced lung disease is usually considered a diagnosis of exclusion of other diseases. The diagnosis of drug-mediated pulmonary toxicity is usually made based on clinical findings. In general, laboratory analyses do not help in establishing the diagnosis. High-resolution computed tomography scanning is more sensitive than chest radiography for defining radiographic abnormalities. The treatment of drug-induced lung disease consists of immediate discontinuation of the offending drug and appropriate management of the pulmonary symptoms. Glucocorticoids have been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. Before starting any medication, patients should be educated about the potential adverse effects of the drug. Amiodarone is an antiarrhythmic agent used in the treatment of many types of tachyarrhythmia. Amiodarone-caused pulmonary toxicity is a well-known side effect (complication) of this medication. The incidence of amiodarone-induced lung disease is approximately 5-7%.

Illness perception in tuberculosis by implementation of the Brief Illness Perception Questionnaire - a TBNET study.

How patients relate to the experience of their illness has a direct impact over their behavior. We aimed to assess illness perception in patients with pulmonary tuberculosis (TB) by means of the Brief Illness Perception Questionnaire (BIPQ) in correlation with patients' demographic features and clinical TB score. Our observational questionnaire based study included series of consecutive TB patients enrolled in several countries from October 2008 to January 2011 with 167 valid questionnaires analyzed. Each BIPQ item assessed one dimension of illness perceptions like the consequences, timeline, personal control, treatment control, identity, coherence, emotional representation and concern. An open question referred to the main causes of TB in each patient's opinion. The over-all BIPQ score (36.25 ± 11.054) was in concordance with the clinical TB score (p ≤ 0.001). TB patients believed in the treatment (the highest item-related score for treatment control) but were unsure about the illness identity. Illness understanding and the clinical TB score were negatively correlated (p < 0.01). Only 25% of the participants stated bacteria or TB contact as the first ranked cause of the illness. For routine clinical practice implementation of the BIPQ is convenient for obtaining fast and easy assessment of illness perception with potential utility in intervention design. This time saving effective personalized approach may improve communication with TB patients and contribute to better behavioral strategies in disease control.

[Amiodarone pulmonary toxicity: case report].

INTRODUCTION: Amiodarone, an antiarrhythmic drug, which contains iodine compound, has a tendency to accumulate in some organs including the lungs.This is age, drug dosage and therapy duration dependent. CASE OUTLINE: We present a case of a 73-year-old man, a smoker, who was admitted as emergency case due to severe dyspnea, tachypnea with signs of cyanosis and respiratory insufficiency. Chest x-ray revealed bilateral diffuse pulmonary shadows in the middle and upper parts of the lungs, similar to those in tuberculosis. His illness history showed chronic obstructive pulmonary disease, arterial hypertension, and atrial fibrillation which has been treated with amiodarone for six years. Sputum smears were negative for mycobacteria, and by the diagnostic elimination method for specific, non-specific and malignant disease the diagnosis of amiodarone pulmonary toxicity was made. Fiberoptic bronchoscopy and pathohistological findings of bronchiolitis obliterans organizing pneumonia confirmed the diagnosis. As the first therapeutic approach, amiodarone therapy was stopped.Then, systemic therapy with methylprednisolone 21 (sodium succinate) 40 mg i.v. daily during the first two weeks was initiated and continued with daily dose of methylprednisolone 30 mg orally during the next three months. The patient showed a marked subjective improvement during the first week, which was followed by the improvement of respiratory function and withdrawal of pulmonary changes with complete radiographic and CT resolution after eight months. CONCLUSION: Amiodarone pulmonary toxicity should be taken into consideration, especially in elderly patients with respiratory symptoms and pulmonary changes, even if only a low dose of amiodarone is administred over a longer time period.

Gender differences revealed by the Brief Illness Perception Questionnaire in allergic rhinitis.

BACKGROUND: The increasing prevalence of allergic rhinitis (AR) is reported worldwide. Illness perception (IP) assessment is warranted in current routine clinical practice to assist communication between patients and medical staff, and improve adherence to treatment and disease outcome. OBJECTIVE: To investigate a group of patients with AR in terms of their IP by the Brief Illness Perception Questionnaire (BIPQ) and to correlate the findings with demographic and clinical features. METHODS: In this observational questionnaire-based study, a successive series of patients treated for AR at the Allergology and Immunology Teaching Hospital, Clinical Centre of Serbia in Belgrade, were enrolled from September 2010 to January 2011, and 93 valid questionnaires were analyzed. Each item of the BIPQ assessed one dimension of IP like the consequences, timeline, personal control, treatment control, identity, coherence, emotional representation and concern. RESULTS: The patients' average age: 35.25 ± 12.42; male/female ratio: 0.79; the overall BIPQ score = 34.69 ± 11.89. The highest item-related scores were found for treatment control (8.17 ± 2.28), illness understanding (7.34 ± 2.96) and emotional representation (6.30 ± 3.45), and the lowest for identity (4.8 ± 2.78) and affection (4.83 ± 2.65). Women compared with men perceive AR as a significantly more threatening disease (P = 0.04). No significant correlation between the BIPQ total or item-related scores was found for any other demographic or clinical feature. CONCLUSION: The BIPQ, which allows rapid assessment of IP and reveals gender differences in AR, is a convenient tool for use in routine clinical practice. Further investigation is needed to demonstrate how IP may influence patients' behavior in AR, treatment adherence and disease outcome.

Clinical and radiological manifestations of primary tracheobronchial tumours: a single centre experience.

INTRODUCTION: Tracheobronchial tumours usually cause an airway obstruction and secondary pulmonary infections. Although rare, they are an important differential diagnosis as they may mimic other conditions and diseases. This paper aims to analyse clinical, radiological and histological characteristics of the patients with tracheobronchial tumours diagnosed for a period of 7 years. MATERIALS AND METHODS: In this retrospective, observational study, we carefully reviewed 65 patients who were diagnosed with tracheal and endobronchial tumours, and performed statistical analysis on the results. RESULTS: Among these 65 patients (36 men and 29 women) with a mean age of 48.8 years (range, 15 to 75), 50 had malignant tumours while 15 had benign ones. The most common symptoms were cough, chest pain and haemoptysis. Cough was a more frequent symptom in patients with benign tumours (P <0.0014). Only 2 patients were asymptomatic. Tumours were predominantly localised in the large airways (46 in large bronchi and 2 in trachea). The most common radiological manifestation of malignant tumours was tumour mass (46%) followed by atelectasis. One third benign tumour caused atelectasis, while tumour mass and consolidation were found in 3 patients each. Computerised tomography revealed endoluminal tumour mass in 29.2% of the cases, which was more frequently found in benign than malignant tumours (47% vs 24%, respectively). On bronchoscopy, tumours were visible in 73% and 70% benign and malignant cases respectively. CONCLUSION: Tracheobronchial tumours should be ruled as a possible diagnosis in patients with cough, haemoptysis, dyspnoea and chest pain. The imaging techniques and histological examination of the tissue would subsequently lead to correct diagnosis and proper treatment can be administered.

Symptoms of anxiety and depression in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Despite the prevalence and importance of anxiety and depressive symptoms in chronic obstructive pulmonary disease (COPD) patients, procedures for routine screening in therapeutic protocols are not commonly used. OBJECTIVE: to assess the symptoms of anxiety and depression in COPD patients and to evaluate their relation to patients' demographic parameters and clinical characteristics. METHODS: The research included 40 COPD patients, treated at the Institute of Lung Diseases and Tuberculosis, Clinical Centre Serbia in Belgrade, from November 2010 to February 2011. Study data were assessed by the questionnaire designed for the purposes of the present study together with Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating Scale (HDRS). RESULTS: Mean HARS score was 10.7 (SD=6.5) (22.5% subjects scored > or = 17) and mean HDRS score was 10.7 (SD=8.2) (20.0% subjects scored > or = 17). Depression was significantly higher in women (Z=-1.971: p=0.049). Lower value of forced expiratory volume in one second (FEV1) correlated with higher HDRS score (p=-0.321; p=0.042). The incidence of anxiety and depression symptoms is higher in patients with more hospitalizations and longer hospital stay. CONCLUSION: The prevalence and importance of anxiety and depressive symptoms in COPD patients require implementation of a specific questionnaire as the procedure for routine screening in order to detect affective symptoms early and to prevent the progression.

Knowledge and attitudes towards tuberculosis in non medical students University of Belgrade.

BACKGROUND: Population's knowledge on tuberculosis (TB) is crucial in early seeking of medical care. Delay in diagnosis for any reason contributes to advanced forms and TB transmission in the community. Knowledge about TB in general population of Serbia is poor, including vulnerable groups. AIM: to assess knowledge about TB in a group of non medical students in University of Belgrade, their attitudes towards TB patients, sources of medical information they use or desire. METHODS: Observational, questionnaire based study. University students of the Faculty of Organizational Science and Faculty of Geography completed the 27-item questionnaires voluntarily and anonymously. The questions related to TB etiology, way of transmission, risk factors and the source of health information students preffer. Statistical analysis was performed. RESULTS: All the participants (69 students aged 20 +/- 0.777 years, 69.7% male, 30.3% female) previously heard about TB, mostly describing it as pulmonary disease. Only 22 (31.88%) selected bacillus as the only cause of TB, and 20% selected answer "I do not know". TB is curable (95%). One third does not know about TB symptoms and 45/69 (65%) think that TB is an infectious disease. Majority (78.3%) would pay visit to TB patient, 1/2 with fear of infection that is in positive correlation with knowledge on infectiousness (p=0.041). Television is the most common used source of health information. Students have the greatest confidence in doctors' information. CONCLUSION: Students' knowledge on TB is inadequate, especially on its cause and way of transmission. More effort is needed in university students' health education.