ObjectivesThis study aimed to assess the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with any of the ...commercially available tumour necrosis factor inhibitors (TNFis) in Slovenia.DesignThis is a cohort, registry (biorx.si) cross-linked with the Slovenian National TB Registry.SettingNational, involving all Slovenian rheumatology centres (six secondary and two secondary/tertiary).Participants2429 patients with RA, AS or PsA exposed to at least one TNFi participated in the study.Primary and secondary outcome measuresThe primary outcome measures were age-adjusted and sex-adjusted TB incidence rates (IRs) and the standardised incidence ratios (SIRs) compared with the general population exploring different TNFi exposure windows. The secondary outcome measures were a detailed characterisation of the national latent tuberculosis infection (LTBI) screening and TB chemoprophylaxis protocol implementation.ResultsAmong the 2429 patients exposed to at least one TNFi for a total of 10 445 (49% RA, 33% AS and 18% PsA) person-years (PY), 99% completed LTBI screening and 6% required TB chemoprophylaxis. Six RA (three adalimumab, three certolizumab), two PsA (two golimumab) and zero AS patients developed TB. Five out of eight had miliary TB, three out of eight had pulmonary TB and two patients died. The age-standardised and sex-standardised TB IR (95% CI) per 100 000 PYs/SIRs (95% CI) compared with the general Slovenian population for the current TNFi exposure were 52 (0 to 110)/6.7 (0.6 to 80), 47 (0 to 110)/6.1 (0.3 to 105), 45 (0 to 109)/5.8 (0.3 to 112) overall, in RA and PsA, respectively.ConclusionsThe TB IR in the Slovenian patients with RA, AS and PsA treated with TNFi was comparable with TB IRs in TB non-endemic countries with less than a tenth of the patients requiring TB chemoprophylaxis.
The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood.
A longitudinal prospective cohort of hospitalised ...patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors.
Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgG
T
B
NK
IL-6
and the anti-S1-IgG
T
B
NK
IL-6
had a high risk of fatal COVID-19 (HR 3.36-21.69; 95% CI 1.51-163.61 and HR 8.39-10.79; 95% CI 1.20-82.67; p≤0.03, respectively). The anti-S1-IgG
T
B
NK
IL-6
and anti-S1-IgG
T
B
NK
IL-6
cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgG
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B
NK
IL-6
and anti-S1-IgG
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B
NK
IL-6
clusters were characterised by a very low risk of mortality.
By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.
To evaluate the access to comprehensive diagnostics and novel antituberculosis medicines in European countries.
We investigated the access to genotypic and phenotypic Mycobacterium tuberculosis drug ...susceptibility testing and the availability of antituberculosis drugs and calculated the cost of drugs and treatment regimens at major tuberculosis treatment centres in countries of the WHO European region where rates of drug-resistant tuberculosis are the highest among all WHO regions. Results were stratified by middle-income and high-income countries.
Overall, 43 treatment centres from 43 countries participated in the study. For WHO group A drugs, the frequency of countries with the availability of phenotypic drug susceptibility testing was as follows: (a) 75% (30/40) for levofloxacin, (b) 82% (33/40) for moxifloxacin, (c) 48% (19/40) for bedaquiline, and (d) 72% (29/40) for linezolid. Overall, of the 43 countries, 36 (84%) and 24 (56%) countries had access to bedaquiline and delamanid, respectively, whereas only 6 (14%) countries had access to rifapentine. The treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was available only in 17 (40%) of the 43 countries. The median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for 6 months), and extensively drug-resistant tuberculosis (including bedaquiline, delamanid, and a carbapenem) were €44 (minimum–maximum, €15–152), €764 (minimum–maximum, €542–15152), and €8709 (minimum–maximum, €7965–11759) in middle-income countries (n = 12) and €280 (minimum–maximum, €78–1084), €29765 (minimum–maximum, €11116–40584), and €217591 (minimum–maximum, €82827–320146) in high-income countries (n = 29), respectively.
In countries of the WHO European region, there is a widespread lack of drug susceptibility testing capacity to new and repurposed antituberculosis drugs, lack of access to essential medications in several countries, and a high cost for the treatment of drug-resistant tuberculosis.
BackgroundProgress towards the World Health Organization's End TB Strategy is monitored by assessing tuberculosis (TB) incidence, often derived from TB notification, assuming complete case detection ...and reporting. This assumption is unlikely to hold in many settings, including European Union (EU) countries.AimWe aimed to assess observed and estimated completeness of TB notification through inventory studies and capture-recapture (CRC) methodology in six EU countries: Croatia, Denmark, Finland, the Netherlands, Portugal Slovenia.MethodsWe performed record linkage, case ascertainment and CRC analyses of data collected retrospectively from at least three national TB-related registers in each country between 2014 and 2016.ResultsObserved completeness of TB notification by inventory studies was 73.9% in Croatia, 98.7% in Denmark, 83.6% in Finland, 81.6% in the Netherlands, 85.8% in Portugal and 100% in Slovenia. Subsequent CRC analysis estimated completeness of TB notification to be 98.4% in Denmark, 76.5% in Finland and 77.0% in Portugal. In Croatia, CRC analyses produced implausible results while in the Netherlands and Slovenia, it was methodologically considered not meaningful.ConclusionInventory studies and CRC methodology suggest a TB notification completeness between 73.9% and 100% in the six EU countries. Mandatory reporting by clinicians and laboratories, and cross-checking of registers, strongly contributes to accurate notification rates, but hospital episode registers likely contain a considerable proportion of false-positive TB records and are thus less useful. Further strengthening routine surveillance to count TB cases, i.e. incidence, accurately by employing record-linkage of high-quality TB registers should make CRC studies obsolete in EU countries.
BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born ...individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.
Background: Progress towards the World Health Organization's End TB Strategy is monitored by assessing tuberculosis (TB) incidence, often derived from TB notification, assuming complete case ...detection and reporting. This assumption is unlikely to hold in many settings, including European Union (EU) countries. Aim: We aimed to assess observed and estimated completeness of TB notification through inventory studies and capture–recapture (CRC) methodology in six EU countries: Croatia, Denmark, Finland, the Netherlands, Portugal Slovenia. Methods: We performed record linkage, case ascertainment and CRC analyses of data collected retrospectively from at least three national TB-related registers in each country between 2014 and 2016. Results: Observed completeness of TB notification by inventory studies was 73.9% in Croatia, 98.7% in Denmark, 83.6% in Finland, 81.6% in the Netherlands, 85.8% in Portugal and 100% in Slovenia. Subsequent CRC analysis estimated completeness of TB notification to be 98.4% in Denmark, 76.5% in Finland and 77.0% in Portugal. In Croatia, CRC analyses produced implausible results while in the Netherlands and Slovenia, it was methodologically considered not meaningful. Conclusion: Inventory studies and CRC methodology suggest a TB notification completeness between 73.9% and 100% in the six EU countries. Mandatory reporting by clinicians and laboratories, and cross-checking of registers, strongly contributes to accurate notification rates, but hospital episode registers likely contain a considerable proportion of false-positive TB records and are thus less useful. Further strengthening routine surveillance to count TB cases, i.e. incidence, accurately by employing record-linkage of high-quality TB registers should make CRC studies obsolete in EU countries.
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.
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.
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.
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.
BACKGROUND The effectiveness and feasibility of a comprehensive strategy to reduce nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in a highly endemic setting have not ...yet been proved. Limited benefits and the high cost of such programs are the main concerns. METHODS We prospectively evaluated the effect of an aggressive infection control program on transmission of MRSA in the University Clinic of Respiratory and Allergic Diseases. All patients with MRSA carriage during 5 years (January 1, 1998, through December 31, 2002) were included and categorized into imported or hospital-acquired cases. RESULTS Methicillin-resistant S aureus was recovered from 223 hospitalized patients; 142 cases were imported and 81 were acquired at our institution. After introduction of the comprehensive infection control program in 1999, the annual incidence of MRSA carriage per 1000 admissions increased from 4.5 in 1998 to 8.0 in 1999 (P = .02), and remained stable thereafter. In this period, the proportion of MRSA cases acquired in our institution decreased from 50.0% in 1999 to 6.1% in 2002 (P<.001), whereas the proportion of MRSA cases transferred from other hospitals (P<.001) and nursing homes (P = .03) increased. All 19 MRSA carriers with 3 sets of follow-up cultures were successfully decolonized. CONCLUSIONS With a comprehensive infection control program, it was possible to reduce nosocomial transmission of MRSA in a highly endemic setting. With good hand hygiene using alcohol handrub, early detection, isolation, and a decolonization strategy, containment of MRSA was achievable, despite a high rate of transferred patients with MRSA.Arch Intern Med. 2004;164:2038-2043-->
Background. This prospective cohort study presents the effectiveness and feasibility of a comprehensive control strategy to reduce nosocomial transmission of methicillinresistant Staphylococcus ...aureus (MRSA) in a highly endemic setting.Methods. All patients with MRSA carriage admitted to the University Clinic of Respiratory and Allergic Diseases over a period of 5 years (January 1998 through December 2002) were included and categorized into imported or hospitalacquired cases. In January 1999, an aggressive infection control program was implemented. It was focused on promoting alcohol hand rub, obtaining active surveillance cultures for MRSA, implementing strict barrier precautions and decolonizing MRSA carriers.Results. MRSA was recovered from 223 hospitalized patients; 142 cases were imported and 81 were acquired at our institution. After the introduction of an active surveillance program, the annual incidence of detected MRSA carriage per 1000 admissions first increased from 4.5 in 1998 to 8.0 in 1999 (p = 0.019), but remained stable thereafter. The proportion of patients detected through active surveillance cultures progressively increased from 23% in 1999 to 78% in 2002. Since 1999, the proportion of acquired MRSA cases in our institution has steadily decreased from 50% in 1999 to 6% in 2002 (p < 0.001), whereas the proportion of patients who acquired MRSA in other hospitals (p < 0.001) and nursing homes (p = 0.025) has increased.Conclusions. With a comprehensive infection control program it is possible to substantially reduce nosocomial transmission of MRSA in a highly endemic area. With good hand hygiene, early detection, isolation and decolonization strategy, containment of MRSA is achievable despite a high rate of transferred patients colonized or infected with MRSA from other healthcare facilities.
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