Tuberculosis in Poland in 2020.

AIM OF THE STUDY: To evaluate the main features of epidemiology of tuberculosis (TB) in 2020 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. MATERIAL AND METHODS: Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2020, data from Statistics Poland on deaths from tuberculosis in 2019, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2020 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." RESULTS: In 2020, 3,388 TB cases were reported in Poland. The incidence rate was 8.8 cases per 100,000 with large variability between voivodeships from 5.5 to 13.3 per 100,000. A decrease in the incidence was found in 15 voivodeships, the most significant in Slaskie voivodship (63.9%). The number of all pulmonary tuberculosis cases was 3,237 i.e. 8.4 per 100,000. Pulmonary cases represented 95.5% of all TB cases. In 2020, 151 extrapulmonary TB cases were notified (4.5% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,573 cases (79.5% of all pulmonary TB cases, the incidence rate 6.7 per 100,000). The number of smear-positive pulmonary TB cases was 1,771 i.e. 4.6 per 100,000 (54.7% of all pulmonary TB cases). In 2020, there were 38 cases (15 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.6% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with increasing age from 0.7 per 100,000 among children (0-14 years) to 15.0 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 12.1 per 100,000. There were 39 cases in children up to 14 years of age (1.2% of the total) and 49 cases in adolescents between 15 and 19 years of age - rates 0.7 and 2.7 per 100,000 respectively. In 2020, there were 2,506 cases of tuberculosis in men and 882 in women. The TB incidence in men - 13.5 per 100,000 was 3.0 times higher than among women - 4.5. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 50-54 years - 26.8 vs. 4.1 and in age group 55 to 59 years - 28.7 vs. 4.8. In 2020, there were 116 patients of foreign origin among all cases of tuberculosis in Poland (3.4%). In 2019, TB was the cause of death for 456 people (mortality rate - 1.2 per 100,000). CONCLUSIONS: TB incidence in Poland in 2020 was 36.7% lower than in 2019. Such significant declines in the incidence have not been observed in the last two decades. As in previous years, there were differences in incidence rates between voivodeships with an unexpectedly sharp decrease in incidence in Silesia (Slaskie voivodeship). The percentage of tuberculosis cases with bacteriological confirmation exceeded 78%, more than in EU/EEA countries (67.3%). The percentage of MDR-TB cases was still lower than the average in EU/EEA countries (1.6% vs. 3.8%). The highest incidence rates were found in Poland in the older age groups (EU/EEAaged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.2%, less than the average in EU/EEA countries (3.8%). The incidence of tuberculosis in men was three times higher than in women in Poland, and six times higher in patients aged 50 to 59. The impact of migration on the TB pattern in Poland has not yet become significant in 2020. The percentage of foreigners among TB patients was 3.4% (33% in EU/EEA countries).

Current therapeutic delivery approaches using nanocarriers for the treatment of tuberculosis disease.

Tuberculosis is a major health issue globally and a leading cause of death due to the infective microorganism Mycobacterium tuberculosis. Treatment of drug resistance tuberculosis requires longer treatment with multiple daily doses of drugs. Unfortunately, these drugs are often associated with poor patient compliance. In this situation, a need has been felt for the less toxic, shorter, and more effective treatment of the infected tuberculosis patients. Current research to develop novel anti-tubercular drugs shows hope for better management of the disease. Research on drug targeting and precise delivery of the old anti-tubercular drugs with the help of nanotechnology is promising for effective treatment. This review has discussed the status currently available treatments for tuberculosis patients infected with Mycobacterium alone or in comorbid conditions like diabetes, HIV and cancer. This review also highlighted the challenges in the current treatment and research on the novel anti-tubercular drugs to prevent multi-drug-resistant tuberculosis. It presents the research highlights on the targeted delivery of anti-tubercular drugs using different nanocarriers for preventing multi-drug resistant tuberculosis. Report has shown the importance and development of the research on nanocarriers mediated anti-tubercular delivery of the drugs to overcome the current challenges in tuberculosis treatment.

Multidrug-Resistant TB (MDR-TB) and Extensively Drug-Resistant TB (XDR-TB) Among Children: Where We Stand Now.

Drug-resistant tuberculosis (DR-TB) has continued to be a global health cataclysm. It is an arduous condition to tackle but is curable with the proper choice of drug and adherence to the drug therapy. WHO has introduced newer drugs with all-oral shorter regimens, but the COVID-19 pandemic has disrupted the achievements and raised the severity. The COVID-19 controlling mechanism is based on social distancing, using face masks, personal protective equipment, medical glove, head shoe cover, face shield, goggles, hand hygiene, and many more. Around the globe, national and international health authorities impose lockdown and movement control orders to ensure social distancing and prevent transmission of COVID-19 infection. Therefore, WHO proposed a TB control program impaired during a pandemic. Children, the most vulnerable group, suffer more from the drug-resistant form and act as the storehouse of future fatal cases. It has dire effects on physical health and hampers their mental health and academic career. Treatment of drug-resistant cases has more success stories in children than adults, but enrollment for treatment has been persistently low in this age group. Despite that, drug-resistant childhood tuberculosis has been neglected, and proper surveillance has not yet been achieved. Insufficient reporting, lack of appropriate screening tools for children, less accessibility to the treatment facility, inadequate awareness, and reduced funding for TB have worsened the situation. All these have resulted in jeopardizing our dream to terminate this deadly condition. So, it is high time to focus on this issue to achieve our Sustainable Development Goals (SDGs), the goal of ending TB by 2030, as planned by WHO. This review explores childhood TB's current position and areas to improve. This review utilized electronic-based data searched through PubMed, Google Scholar, Google Search Engine, Science Direct, and Embase.

Challenges of diabetes in elderly TB patients.

Diabetes mellitus (DM) and tuberculosis (TB) are worldwide health burdens post-COVID-19. TB is the second-leading cause of death by a single infectious microbe. There is much evidence around the world about the responsibility of TB-DM co-morbidity. Both TB and DM prevalence is high in low- and middle-income countries. Especially the elderly with diabetes are more prone to TB infection due to compromised immune systems. Diabetic patients are three times as likely to develop tuberculosis as non-diabetic patients. DM interferes with the status of TB and leads to undesirable outcomes in the treatment of TB. This may later lead to the development of multidrug-resistant tuberculosis (MDR-TB). The coexistence of TB and DM leads to a high mortality rate and therefore becomes an enormous challenge for the medical field. This viewpoint includes the most current information about TB and DM, disease complications, treatment strategies, challenges to be faced in disease management and the importance of TB-DM bidirectional screening in older adults, which helps in early detection and better treatment programme.

The surfactant inhaled therapy in a complex lung tuberculosis treatment: clinical reviews

The article describes the clinical case reports of patients with respiratory tuberculosis who were hospitalized at the Regional Clinical Antituberculosis Center in Kursk. One of them was in the pediatric department for patients with tuberculosis of respiratory organs and the other in the 1st department for patients with multidrug-resistant tuberculosis. As pathogenetic therapy in the complex treatment of pulmonary tuberculosis, in the intensive phase of anti-tuberculosis chemotherapy, we added inhalation therapy with surfactant (medicinal product surfactant-BL lyophilisate for emulsion preparation, 75 mg, manufactured by Biosurf LLC, Russia) according to the instructions to the drug. Treatment of pulmonary tuberculosis is performed by multiple inhalations of surfactant-BL as part of complex therapy against the background of fully deployed antituberculosis drugs (ATD), i.e. when the patient empirically or based on data on drug sensitivity of the pathogen is selected 4-6 ATD that are well tolerated by the patient in the prescribed dose and combination. It should be noted that an adult patient during the intensive phase of anti-tuberculosis chemotherapy had COVID-19. Against the background of inhalation therapy with surfactant, it was possible to stabilize the clinical and radiological condition of the patients, and to improve their condition. Clinically it was expressed in reduction of coughing, increase of tolerance to physical exertion. For example, according to spirometry data on the admission of an adult patient and in dynamics, the vital capacity index (VCI) increased from an extremely sharp decrease (31.25%) to 75%, which corresponded to a very mild decrease. At the moment the patient from the children's ward is completing a course of antituberculosis therapy with small residual changes in the lungs, and the adult patient was operated on at the Russian Ministry of Health at the Federal State Budgetary Institution "National Research Center of Pulmonary Medicine” for installation of a bronchial valve. Based on the above, we can conclude about the successful, pathogenetically sound use of surfactant-BL in patients with respiratory tuberculosis in both children and adults. © 2022, Remedium Group Ltd. All rights reserved.

The surfactant inhaled therapy in a complex lung tuberculosis treatment: clinical reviews

The article describes the clinical case reports of patients with respiratory tuberculosis who were hospitalized at the Regional Clinical Antituberculosis Center in Kursk. One of them was in the pediatric department for patients with tuberculosis of respiratory organs and the other in the 1st department for patients with multidrug-resistant tuberculosis. As pathogenetic therapy in the complex treatment of pulmonary tuberculosis, in the intensive phase of anti-tuberculosis chemotherapy, we added inhalation therapy with surfactant (medicinal product surfactant-BL lyophilisate for emulsion preparation, 75 mg, manufactured by Biosurf LLC, Russia) according to the instructions to the drug. Treatment of pulmonary tuberculosis is performed by multiple inhalations of surfactant-BL as part of complex therapy against the background of fully deployed antituberculosis drugs (ATD), i.e. when the patient empirically or based on data on drug sensitivity of the pathogen is selected 4-6 ATD that are well tolerated by the patient in the prescribed dose and combination. It should be noted that an adult patient during the intensive phase of anti-tuberculosis chemotherapy had COVID-19. Against the background of inhalation therapy with surfactant, it was possible to stabilize the clinical and radiological condition of the patients, and to improve their condition. Clinically it was expressed in reduction of coughing, increase of tolerance to physical exertion. For example, according to spirometry data on the admission of an adult patient and in dynamics, the vital capacity index (VCI) increased from an extremely sharp decrease (31.25%) to 75%, which corresponded to a very mild decrease. At the moment the patient from the children's ward is completing a course of antituberculosis therapy with small residual changes in the lungs, and the adult patient was operated on at the Russian Ministry of Health at the Federal State Budgetary Institution "National Research Center of Pulmonary Medicine” for installation of a bronchial valve. Based on the above, we can conclude about the successful, pathogenetically sound use of surfactant-BL in patients with respiratory tuberculosis in both children and adults. © 2022, Remedium Group Ltd. All rights reserved.

Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. METHODS: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. RESULTS: After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). CONCLUSIONS: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.

MDR-TB in Pakistan: Challenges, efforts, and recommendations.

Tuberculosis (TB), a global health concern is also a leading cause of mortality and morbidity across Pakistan affecting a major proportion of the population. The absence of an integrated system to control the spread of TB has led to a rise in multidrug resistant strains of TB (MDR-Tb) which do not exhibit any sensitivity towards the first line therapy for TB. Such adverse circumstances call for effective planning strategies to mitigate the health hazards of MDR-TB. This article briefly highlights the challenges encountered by the already burdened healthcare system and suggests relatively inexpensive approaches to tackle the ongoing crisis associated with MDR-TB on a national scale.

Tuberculosis the Lernaean Hydra of 21st Century - A Post Covid Update on the Indian Scenario

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Tuberculosis usually affects the lungs, but it can also affect other parts of the body, such as the brain, kidneys, and spine. In most cases, tuberculosis is preventable. However, tuberculosis patients can die if not treated properly. According to the World Health Organization (WHO), tuberculosis (TB) is a worldwide pandemic. It is the primary cause of mortality among HIV-infected individuals. Poor adherence to Tuberculosis treatment can lead to prolonged infection and poor treatment outcomes. Prevention plays a very important role in the fight against TB. Directly Observed Treatment aims to improve adherence to TB treatment by observing patients while they take TB medications. India's DOTS (directly observed treatment short course) program is the world's fastest-growing and biggest in terms of patients beginning on treatment, as well as the second-largest in terms of population coverage. Its purpose is to reduce TB mortality and morbidity while also reducing infection transmission until TB is no longer a serious public health concern in India. Multidrug-resistant tuberculosis (MDR-TB) is caused by organisms that are resistant to at least two of the most potent tuberculosis drugs, isoniazid and rifampicin. Multidrug-resistant tuberculosis (MDR-TB) is an increasing danger to tuberculosis eradication, and it is the outcome of a failing tuberculosis control program. Community-based programs can improve patient outcomes by allowing patients to receive treatment at home and addressing socioeconomic barriers to adherence to treatment. This article discusses about Tuberculosis and the ways to manage tuberculosis.

Pre-Clinical Tools for Predicting Drug Efficacy in Treatment of Tuberculosis.

Combination therapy has, to some extent, been successful in limiting the emergence of drug-resistant tuberculosis. Drug combinations achieve this advantage by simultaneously acting on different targets and metabolic pathways. Additionally, drug combination therapies are shown to shorten the duration of therapy for tuberculosis. As new drugs are being developed, to overcome the challenge of finding new and effective drug combinations, systems biology commonly uses approaches that analyse mycobacterial cellular processes. These approaches identify the regulatory networks, metabolic pathways, and signaling programs associated with M. tuberculosis infection and survival. Different preclinical models that assess anti-tuberculosis drug activity are available, but the combination of models that is most predictive of clinical treatment efficacy remains unclear. In this structured literature review, we appraise the options to accelerate the TB drug development pipeline through the evaluation of preclinical testing assays of drug combinations.

COVID-19 Pandemic Disruption on the Management of Tuberculosis Treatment in Indonesia.

The current coronavirus disease 2019 (COVID-19) situation might deteriorate the efforts to eliminate tuberculosis (TB) in Indonesia. This study aimed to review the COVID-19 pandemic disruption on the management of TB treatment in Indonesia. We identified several disruptions due to the pandemic on TB control management. Firstly, there is a potential decrease in the funding for TB treatment. Financial disruptions caused by the COVID-19 pandemic have led to further setbacks. In many countries, including Indonesia, financial and other resources have been reallocated from TB to the COVID-19 response. Secondly, it has been highlighted that all TB services, including case detection and rapid diagnostic, have been disrupted by the pandemic. Thirdly, the pandemic would be associated with the lower quality of care and treatment for TB in Indonesia. It might decrease the enthusiasm of patients with TB, multi-drug resistant (MDR)-TB, and TB-human immunodeficiency virus (HIV) to visit TB hospitals because of social distancing measures by the government. Finally, the COVID-19 pandemic also has impacted critical activities of monitoring, evaluation, and surveillance. There are several lessons from other countries about managing TB treatment during the pandemic, such as combining screening for COVID-19 and TB by applying x-ray technology and artificial intelligence-based software. In addition, the use of telemedicine or telehealth in TB treatment is also beneficial to deliver medication, assess patients' progress, and inform prevention strategies. To reach the target with the end TB strategy, the government of Indonesia can adopt the World Health Organization's (WHO's) comprehensive strategies, such as integrated, patient-centered TB care and prevention strategies; bold policies and supportive systems; and intensified research and innovations.

Accelerating development of new shorter TB treatment regimens in anticipation of a resurgence of multi-drug resistant TB due to the COVID-19 pandemic.

The WHO 2020 global TB Report estimates that in 2019 there were an estimated 500,000 cases of multi-drug resistant TB (MDR-TB) of which only 186,772 MDR-TB cases were diagnosed, and positive treatment outcomes were achieved in 57% of them. These data highlight the need for accelerating and improving MDR-TB screening, diagnostic, treatment and patient follow-up services. The last decade has seen three new TB drugs being licensed; bedaquiline, delamanid and pretomanid, and combinations these new, existing and repurposed drugs are leading to improved cure rates. The all oral six month WHO regimen for MDR-TB is more tolerable, has higher treatment success rates and lower mortality. However, the unprecedented ongoing COVID-19 pandemic is having major direct and indirect negative impacts on health services overall, including national TB programs and TB services. This adds further to longstanding challenges for tackling MDR-TB such as cost, rollout of diagnostics and drugs, and implementation of latest WHO guidelines for MDR-TB. In light of COVID-19 disruption of TB services, it is anticipated the numbers of MDR-TB cases will rise in 2021 and 2022 and will affect treatment outcomes further. Investing more in development of new TB drugs and shorter MDR-TB treatment regimens is required in anticipation of emerging drug resistance to new TB drug regimens. There is an urgent need for protecting current investments in TB services, sustaining gains being made in TB control and accelerating roll out of TB diagnostic and treatment services.

Multidrug-resistant tuberculosis in COVID-19: Double trouble.

COVID-19 pandemic has changed the lives of many especially those living with chronic diseases. India has the highest burden of multidrug resistant tuberculosis (MDR TB) in the world. The pandemic and the lockdown created multiple bottlenecks in the provision of healthcare as well as the distribution of medications. The stigma of tuberculosis leads to mental trauma, suffering, delay in diagnosis, and non-compliance to therapy. Lockdown imposed due to COVID-19, aggravated the fears of each patient and had made medical care access difficult. Here we describe a patient with MDR TB and chronic hepatitis B and how the course of the disease and its management was affected by COVID-19.

Reducing the risk of tuberculosis transmission for HCWs in high incidence settings.

Globally, tuberculosis (TB) is a leading cause of death from a single infectious agent. Healthcare workers (HCWs) are at increased risk of hospital-acquired TB infection due to persistent exposure to Mycobacterium tuberculosis (Mtb) in healthcare settings. The World Health Organization (WHO) has developed an international system of infection prevention and control (IPC) interventions to interrupt the cycle of nosocomial TB transmission. The guidelines on TB IPC have proposed a comprehensive hierarchy of three core practices, comprising: administrative controls, environmental controls, and personal respiratory protection. However, the implementation of most recommendations goes beyond minimal physical and organisational requirements and thus cannot be appropriately introduced in resource-constrained settings and areas of high TB incidence. In many low- and middle-income countries (LMICs) the lack of knowledge, expertise and practice on TB IPC is a major barrier to the implementation of essential interventions. HCWs often underestimate the risk of airborne Mtb dissemination during tidal breathing. The lack of required expertise and funding to design, install and maintain the environmental control systems can lead to inadequate dilution of infectious particles in the air, and in turn, increase the risk of TB dissemination. Insufficient supply of particulate respirators and lack of direction on the re-use of respiratory protection is associated with unsafe working practices and increased risk of TB transmission between patients and HCWs. Delayed diagnosis and initiation of treatment are commonly influenced by the effectiveness of healthcare systems to identify TB patients, and the availability of rapid molecular diagnostic tools. Failure to recognise resistance to first-line drugs contributes to the emergence of drug-resistant Mtb strains, including multidrug-resistant and extensively drug-resistant Mtb. Future guideline development must consider the social, economic, cultural and climatic conditions to ensure that recommended control measures can be implemented in not only high-income countries, but more importantly low-income, high TB burden settings. Urgent action and more ambitious investments are needed at both regional and national levels to get back on track to reach the global TB targets, especially in the context of the COVID-19 pandemic.

COVID-19 -Tuberculosis interactions: When dark forces collide.

The SARS-2 pandemic which has moved with frightening speed over the last 5 months has several synergies with another older, and far more neglected airborne disease, tuberculosis. Patients with tuberculosis are not only more likely to be infected by SARS-CoV-2 but also likely to have adverse outcomes once infected. The sequelae of more severe forms of COVID-19 in patients who have recovered from TB but have residual compromised lung function, are also likely to be devastating. These diseases share almost identical bio-social determinants like poverty, overcrowding, diabetes and pollution and some clinical similarities. The consequences of the COVID-19 pandemic, and our global response to it with lockdowns, are likely to leave a profound and long-lasting impact on TB diagnosis and control, potentially leading to an additional 6.3 million cases of TB between 2020 and 2025, and an additional 1.4 million TB deaths during this time. Novel solutions will need to be urgently devised or else TB control targets will never be met and indeed may be set back by 5-8 years.

Tuberculosis among prisoners & health care workers.

TB in prisons and among HCW is a major public health concern in countries having high burden of disease. Prompt detection of TB is must in prisons by screening on entry, passive screening, mass screening and contact screening via clinical evaluation, smear microscopy and chest X-rays. The new rapid diagnostic methods - True-NAAT, CBNAAT and Line Probe Assay are important tools in the diagnosis. Implementation of effective preventive measures at every steps in various settings, along with airborne infection control and protective measures for staff must be ensured.

Challenges in Tuberculosis Clinical Trials in the Face of the COVID-19 Pandemic: A Sponsor's Perspective.

The COVID-19 pandemic has caused unforeseen and extreme changes in societal and health system functioning not previously experienced in most countries in a lifetime. The impact of the pandemic on clinical trials can be especially profound given their complexities and operational requirements. The STREAM Clinical Trial is the largest trial for MDR-TB ever conducted. Currently operating in seven countries, the trial had 126 participants on treatment and 312 additional participants in active follow up as of March 31, 2020. Areas of particular concern during this global emergency include treatment continuity, supply chain management and participant safety monitoring. This commentary highlights some of the challenges faced due to the pandemic and the steps taken to protect the safety of trial participants and the integrity of the trial.