To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic.
This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission.
582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 7% patients), followed by remdesivir (17 3% patients), lopinavir-ritonavir (six 1% patients), and oseltamivir (three 1% patients). Immunomodulatory medication used included corticosteroids (22 4% patients), intravenous immunoglobulin (seven 1% patients), tocilizumab (four 1% patients), anakinra (three 1% patients), and siltuximab (one <1% patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support.
COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed.
ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.
This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out ...priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.
Tuberculosis is a major global health issue, with approximately 10 million people falling ill and 1.4 million dying yearly. One of the most significant challenges to public health is the emergence of ...drug-resistant tuberculosis. For the last half-century, treating tuberculosis has adhered to a uniform management strategy in most patients. However, treatment ineffectiveness in some individuals with pulmonary tuberculosis presents a major challenge to the global tuberculosis control initiative. Unfavorable outcomes of tuberculosis treatment (including mortality, treatment failure, loss of follow-up, and unevaluated cases) may result in increased transmission of tuberculosis and the emergence of drug-resistant strains. Treatment failure may occur due to drug-resistant strains, non-adherence to medication, inadequate absorption of drugs, or low-quality healthcare. Identifying the underlying cause and adjusting the treatment accordingly to address treatment failure is important. This is where approaches such as artificial intelligence, genetic screening, and whole genome sequencing can play a critical role. In this review, we suggest a set of particular clinical applications of these approaches, which might have the potential to influence decisions regarding the clinical management of tuberculosis patients.
Nontuberculous mycobacteria (NTM) are opportunistic human pathogens found worldwide, primarily in the environment. They predominantly affect the lungs, especially in individuals with compromised ...immune systems. Recent studies suggest an increasing incidence of NTM disease; however, their actual clinical impact in Slovakia remains uncertain. In this study, we conducted a retrospective analysis using a representative collection of NTM cases in the country. We searched the national database for patients with positive NTM cultures between January 2016 and December 2021. A total of 1355 NTM-positive cultures were identified in Slovakia, with no significant increase observed during the study period. Among these, 358 cases (26.4%) were confirmed as NTM disease. The incidence of the disease was notably higher in individuals over 55 years old (p < 0.0001). Moreover, women diagnosed with NTM disease exhibited a significantly higher average age than men (p = 0.0005). The majority of NTM disease cases were attributed to Mycobacterium (M.) intracellulare (39.9%) and M. avium (38.5%). Geographically, the highest incidence of NTM disease was observed in the Bratislava region (10.69 per 100,000 population).
•Compared to other European countries, Slovakia is among the countries with the highest prevalence of NTM disease.•Since 2010, there has been a significant upward trend in the incidence of NTM diseases.•Results indicating significant changes in the circulation of individual NTM strains in recent years.•The incidence rate for NTM disease was significantly higher in age groups 55–64 and > 65.
Rationale
Tuberculosis (TB) remains a challenging global infectious disease, mainly affecting the lungs. First‐line anti‐TB drugs play a crucial role in slowing down the rapid spread of TB. In ...addition, the patient might benefit from therapeutic drug monitoring since it has become an accepted clinical tool for optimizing TB treatment.
Methods
A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed to monitor the plasma level of isoniazid, ethambutol and pyrazinamide in plasma samples. A one‐step extraction procedure using an Ostro™ plate was applied, and extracts were analyzed by gradient elution followed by detection on a mass spectrometer by multiple reaction monitoring mode.
Results
The analytes were separated within 4.2 min and over the concentration range of 0.2–10 μg/ml for isoniazid and ethambutol and 1–65 μg/ml for pyrazinamide. The method was successfully validated according to the European Medicine Agency guideline for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability, and applied for quantification of analytes in clinical samples from TB patients.
Conclusions
The presented method allows sensitive and reproducible determination of selected anti‐TB drugs with advantages such as low sample volume requirement, short run time of analysis, one‐step sample preparation procedure with capabilities for phospholipids removal, and a low quantification limit as well as a high degree of selectivity.
The International Standards for Tuberculosis Care define the essential level of care for managing patients who have or are presumed to have tuberculosis, or are at increased risk of developing the ...disease. The resources and capacity in the European Union (EU) and the European Economic Area permit higher standards of care to secure quality and timely TB diagnosis, prevention and treatment. On this basis, the European Union Standards for Tuberculosis Care (ESTC) were published in 2012 as standards specifically tailored to the EU setting. Since the publication of the ESTC, new scientific evidence has become available and, therefore, the standards were reviewed and updated.A panel of international experts, led by a writing group from the European Respiratory Society (ERS) and the European Centre for Disease Prevention and Control (ECDC), updated the ESTC on the basis of new published evidence. The underlying principles of these patient-centred standards remain unchanged. The second edition of the ESTC includes 21 standards in the areas of diagnosis, treatment, HIV and comorbidities, and public health and prevention.The ESTC target clinicians and public health workers, provide an easy-to-use resource and act as a guide through all the required activities to ensure optimal diagnosis, treatment and prevention of TB.
The numbers of patients with tuberculosis (TB) caused by resistant strains are still alarming. Therefore, it is necessary to determine resistance more quickly and precisely, than it is with the ...currently used phenotypic and genotypic methods. In recent years, technological advances have been made and the whole-genome sequencing (WGS) method has been introduced as a part of routine diagnostics in clinical laboratories. Comparing a wide range of mycobacterial genomic variations with a reference genome leads to a consistent evaluation of molecular-epidemiology and resistance of Mycobacterium tuberculosis (M. tuberculosis) to a wide range of anti-TB drugs. The quality of the obtained sequencing data is closely related to the type of sample and the method used for DNA extraction and sequencing library preparation. Moreover, the correct interpretation of results is also influenced by a bioinformatic data processing. A large number of bioinformatics pipelines are currently available, the sensitivity of which varies due to the different sizes of databases containing relevant mutations. This review focuses on the individual steps included in the sequencing workflow and factors that may affect the interpretation of final results.
Infections caused by non-tuberculous mycobacteria (NTM) have been a public health problem in recent decades and contribute significantly to the clinical and economic burden globally. The diagnosis of ...infections is difficult and time-consuming and, in addition, the conventional diagnostics tests do not have sufficient discrimination power in species identification due to cross-reactions and not fully specific probes. However, technological advances have been made and the whole genome sequencing (WGS) method has been shown to be an essential part of routine diagnostics in clinical mycobacteriology laboratories. The use of this technology has contributed to the characterization of new species of mycobacteria, as well as the identification of gene mutations encoding resistance and virulence factors. Sequencing data also allowed to track global outbreaks of nosocomial NTM infections caused by M. abscessus complex and M. chimaera. To highlight the utility of WGS, we summarize recent scientific studies on WGS as a tool suitable for the management of NTM-induced infections in clinical practice.
•WHO recommends countries monitor the safety profile of new drugs and regimens.•WHO developed the active TB drug safety monitoring and management (aDSM) package.•aDSM data are not yet available ...globally.•A project to prove aDSM feasibility was launched by the Global Tuberculosis Network; 41 centres in 27 countries participated.•309 cases were fully reported as of February 2019 out of 781 cases countries committed to report in 2019.
The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries.
The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs.
Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile.
A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.
Despite the available diagnostics and treatment, tuberculosis (TB) is a serious infectious disease currently occurring. Even some high-income countries in the world do not fully control it at this ...time. The reason for this situation is the lack of elimination programs to address the situation. The aim of the update of the prediction data was to create a presumption of TB development in Slovakia by 2040.
We used the time series prediction method with exponential equalization. The basis for the calculation were historical data on the incidence of TB from 1960 to 2018 in Slovakia (data for the last 58 yr). This time series has a clearly declining level. In view of this trend, we have set a threshold, whether and when the incidence in the future will fall below 5.0 patients per 100,000 inhabitants.
In case of a favorable development, the limit of our incidence drop below 5.0 cases per 100 000 inhabitants in 2022, when the incidence will be 4.91 per 100 000 inhabitants. In 2040, the predicted incidence of TB should be 1.78 per 100 000 inhabitants. A gradual decline may also be related to a decrease in the population of the Slovak Republic.
Slovakia belongs to those countries of the world where TB is under control. Increased surveillance of high-risk communities through community interventions and countries' readiness for global migration can help to influence factors that may aggravate the epidemiological situation of TB.
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