1. Availability and costs of medicines for the treatment of tuberculosis in EuropeGunar Günther, Lorenzo Guglielmetti, Claude Leu, Christoph Lange, Frank van Leth, 2022, review article Abstract: Objectives. To evaluate the access to comprehensive diagnostics and novel anti-tuberculosis medicines in European countries. Methods. We investigated access to genotypic and phenotypic M. tuberculosis drug susceptibility testing, availability of anti-tuberculosis drugs and calculated cost of drugs and treatment regimens at major tuberculosis treatment centers in countries of the World Health Organization (WHO) European region where rates of drug-resistant tuberculosis are highest among all WHO regions. Results are stratified by middle-income and high-income countries. Results. Overall, 43 treatment centers in 43 countries participated in the study. For WHO Group A drugs, the frequency of countries with availability of phenotypic drug susceptibility testing was as follows: 30/40 (75%) for levofloxacin, 33/40 (82%) for moxifloxacin, 19/40 (48%) for bedaquiline and 29/40 (72%) for linezolid, respectively. Overall, 36/43 (84%) and 24/43 (56%) of countries had access to bedaquiline and delamanid, while only 6/43 (14%) had access to rifapentine. Treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was only available in 17/43 (40%) of the countries. Median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for six months) and extensively drug-resistant tuberculosis (including bedaquiline, delamanid and a carbapenem) were € 44 (min-max € 15-152), € 764 (min-max € 542-15152) and € 8709 (min-max € 7965-11759) in middle-income countries (n=12), and € 280 (min-max-€78-1084), € 29765 (min-max 11116-40584), € 217591 (min-max € 82827-320146) in high-income countries (n=29). Conclusion. In countries of the WHO Europe Region there is a widespread lack of drug susceptibility testing capacity to new and re-purposed anti-tuberculosis drugs, lack of access to essential medications in several countries and high treatment cost for drug-resistant tuberculosis.
Keywords: tuberculosis - drug therapy, Mycobacterium tuberculosis - drug therapy, health care costs - drug therapy, Europe
Published in DiRROS: 31.08.2022; Views: 693; Downloads: 144
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2. Testa QuantiFERON TB in TB Plus v Sloveniji v obdobju 2008–2019Urška Skamen, Eva Sodja, Marija Žolnir-Dovč, 2022, original scientific article Abstract: Izhodišča: Test QuantiFERON TB (QFT TB) je prvenstveno namenjen za odkrivanje latentne (LTBI) okužbe z bacili tuberkuloze (TB). Članek obsega retrospektivno analizo rezultatov testa QFT TB v Sloveniji med letoma 2008 in 2019, opozarja na vplive predanalitskih dejavnikov na rezultate testa ter govori o razlogih za nastanek nejasnih rezultatov in o občutljivosti testa pri bolnikih z aktivno obliko TB. Metode: V obdobju 2008–2019 smo v Laboratoriju za mikobakterije Klinike Golnik s testom QFT TB testirali 29.352 vzorcev krvi bolnikov iz različnih zdravstvenih ustanov v Sloveniji. Na rezultatih testa QFT TB smo izvedli retrospektivno analizo. Rezultati: Delež pozitivnih rezultatov testa QFT TB se z leti postopno znižuje. V letu 2008 je znašal 20,8 %, v letu 2019 pa 10,7 %, kar pomeni, da je v zadnjih dvanajstih letih upadel za 48,6 %. Največjo težavo predstavljajo nejasni rezultati (letno povprečno 4,3 %), saj so za zdravnika nepovedni. Občutljivost testa QFT TB pri bolnikih z aktivno obliko TB je 82,9 %, kar je primerljivo s podatki iz tujine. Zaključek: Pomembno je, da pri odvzemu in pošiljanju krvi dosledno sledimo navodilom, saj je test QFT TB zelo občutljiv na predanalitske dejavnike in klinično stanje preiskovancev. Delež pozitivnih rezultatov testa QFT TB z leti pospešeno upada, kar je povezano z napori za omejitev širjenja TB in upadom primerov aktivne TB v naši državi.
Keywords: tuberkuloza - 2008-2019, Mycobacterium tuberculosis - 2008-2019, latentna tuberkuloza - 2008-2019, Slovenija, test QuantiFERON TB, predanalitski dejavniki, nejasen rezultat
Published in DiRROS: 29.08.2022; Views: 564; Downloads: 177
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3. Next-generation sequencing to characterize pyrazinamide resistance in Mycobacterium tuberculosis isolates from two Balkan countriesEva Sodja, Simon Koren, Nataša Toplak, Sara Truden, Marija Žolnir-Dovč, 2021, original scientific article Abstract: Objectives. Next-generation sequencing (NGS) provide a comprehensive analysis of the genetic alterations that are most commonly linked with pyrazinamide (PZA) resistance. There are no studies reporting molecular background of PZA resistance in TB isolates from Balkan Peninsula. We aimed to examine the feasibility of full-length analysis of a gene linked with PZA resistance, pncA, using Ion Torrent technology in comparison to phenotypic BACTEC MGIT 960 DST in clinical TB isolates from two countries of the Balkan Peninsula. Methods. Between 1996 and 2017, we retrospectively selected 61 TB isolates. To identify gene variants related to drug resistance in genomic DNA extracted from TB isolates, AmpliSeq libraries were generated automatically using the AmpliSeq™ Kit for Chef DL8 and the Ion AmpliSeq TB Research Panel. Result.s Of all 61 TB isolates included, 56 TB were phenotypically resistant to any antibiotic. Among them, 38/56 (67.9%) TB isolates were phenotypically resistant to pyrazinamide and pncA mutations were detected in 33/38 cases (86.8%). A mutation in the pncA promoter region was the most prevalent genetic alteration, detected in eight TB isolates. Comparison of NGS to conventional BACTEC MGIT 960 DST revealed very strong agreement (90.2%) between the two methods in identifying PZA resistance, with high sensitivity (89.5%) and specificity (95.7%) for NGS. Conclusions. Detection of PZA resistance using NGS seems to be a valuable tool for surveillance of TB drug resistance also in the Balkan Peninsula, with great potential to provide useful information at least one weak earlier than is possible with phenotypic DST.
Keywords: tuberculosis, Mycobacterium tuberculosis, high-throughput nucleotide sequencing, pyrazinamide, microbial sensitivity tests, next-generation sequencing, drug susceptibility testing, Slovenia, Republic of North Macedonia
Published in DiRROS: 10.01.2022; Views: 887; Downloads: 542
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4. Tuberculosis among patients treated with TNF inhibitors for rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis in slovenia : a cohort studyŽiga Rotar, Petra Svetina, Matija Tomšič, Alojzija Hočevar, Sonja Praprotnik, 2020, original scientific article Abstract: Objectives: This 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. Design: This is a cohort, registry (biorx.si) cross-linked with the Slovenian National TB Registry. Setting: National, involving all Slovenian rheumatology centres (six secondary and two secondary/tertiary). Participants: 2429 patients with RA, AS or PsA exposed to at least one TNFi participated in the study. Primary and secondary outcome measures: The 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. Results: Among 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. Conclusions: The 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.
Keywords: epidemiology, rheumatology, tuberculosis
Published in DiRROS: 12.11.2020; Views: 1167; Downloads: 560
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5. Mycobacteria in aquarium fish : are fish handlers aware of their zoonotic potential?Mateja Pate, Andrej Ovca, Vlasta Jenčič, Marija Žolnir-Dovč, Matjaž Ocepek, 2019, original scientific article Keywords: fish tank granuloma, fish tuberculosis, mycobacteria, questionnaire, zoonosis
Published in DiRROS: 11.09.2020; Views: 2065; Downloads: 410
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6. Completeness of tuberculosis (TB) notification : inventory studies and capture-recapture analyses, six European Union countries, 2014 to 2016Masja Straetemans, Mirjam I Bakker, Sandra Alba, Christina Mergenthaler, Ente Rood, Peter H Andersen, Henrieke Schimmel, Aleksandar Šimunović, Petra Svetina, Carlos Carvalho, 2020, original scientific article Abstract: 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.
Keywords: Mycobacterium tuberculosis, tuberculosis, incidence, public health surveillance, registries, reporting, notification, data collection, data analysis
Published in DiRROS: 27.07.2020; Views: 1474; Downloads: 1055
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7. Next-generation sequencing of drug resistant Mycobacterium tuberculosis clinical isolates in low-incidence countriesEva Sodja, Nataša Toplak, Simon Koren, Minka Kovač, Sara Truden, Biljana Ilievska Poposka, Marija Žolnir-Dovč, 2019, original scientific article Abstract: Drug resistant tuberculosis (TB), especially multidrug (MDR) and extensively drug-resistant (XDR) TB, is still a serious problem in global TB control. Slovenia and North Macedonia are low-incidence countries with TB incidence rates of 5.4 and 10.4 in 2017, respectively. In both countries, the percentage of drug resistant TB is very low with sporadic cases of MDR-TB. However, global burden of drug-resistant TB continues to increase imposing huge impact on public health systems and strongly stimulating the detection of gene variants related with drug resistance in TB. Next-generation sequencing (NGS) can provide comprehensive analysis of gene variants linked to drug resistance in Mycobacterium tuberculosis. Therefore, the aim of our study was to examine the feasibility of a full-length gene analysis for the drug resistance related genes (inhA, katG, rpoB, embB) using Ion Torrent technology and to compare the NGS results with those obtained from conventional phenotypic drug susceptibility testing (DST) in TB isolates. Between 1996 and 2017, we retrospectively selected 56 TB strains from our National mycobacterial culture collection. Of those, 33 TB isolates from Slovenian patients were isolated from various clinical samples and subjected to phenotypic DST testing in Laboratory for Mycobacteria (University Clinic Golnik, Slovenia). The remaining 23 TB isolates were isolated from Macedonian patients and sent to our laboratory for assistance in phenotypic DST testing. TB strains included were either mono-, poly- or multidrug resistant. For control purposes, we also randomly selected five TB strains susceptible to first-line anti-TB drugs. High concordance between genetic (Ion Torrent technology) and standard phenotypic DST testing for isoniazid, rifampicin and ethambutol was observed, with percent of agreement of 77%, 93.4% and 93.3%, sensitivities of 68.2%, 100% and 100%, and specificities of 100%, 80% and 88.2%, respectively. In conclusion, the genotypic DST using Ion Torrent semiconductor NGS successfully predicted drug resistance with significant shortening of time needed to obtain the resistance profiles from several weeks to just a few days.
Keywords: drug resistant tuberculosis, next-generation sequencing, low-incidence countries, phenotypic drug susceptibility testing
Published in DiRROS: 24.07.2020; Views: 1852; Downloads: 1039
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