Promocijas darbs

Elektroniskā versija nesatur pielikumusAnotacija Ixodidae dzimtas erces ir pasaule pazistamas ka daudzveidigu cilveku un dzivnieku patogenu cirkulacijas uzturetajas daba. Musu valsti noverotas vairakas Ixodidae dzimtas sugas, tomer epidemiologiska nozime lidz šim konstateta tikai divam Ixodidae dzimtas Ixodes gints ercem: Ixodes ricinus L., kas izplatita visa valsts teritorija, retak tas austrumdala, kur domine Ixodes persulcatus P. Sch. Latvija tiek registreta iedzivotaju saslimstiba ar tris šo ercu parnesatam infekcijas slimibam - ercu encefalitu, Laima boreliozem un ari ar erlihiozi (anaplazmozi). Ši petijuma galvenais merkis bija noskaidrot Ixodidae epidemiologiski nozimigo ercu sugu izplatibu, to parnesato infekcijas slimibu nozimi un molekularo epidemiologiju Latvija. Šeit apkopoti un analizeti ilggadigi statistikas dati un kopš 1995. gada praktiski izdaritie noverojumi ercu parnesto slimibu dabas pereklos, to saistiba ar saslimstibas tendencem, veikta Ixodes ercu aktivitates un izplatibas ilggadigas tendences ietekmejušo faktoru izpete, ka ari apskatiti atsevišku Ixodes ercu parnesto patogeno un neskaidras patogenitates mikroorganismu sugu molekularie petijumi ar merki noskaidrot to izplatibu un sastopamibu Latvija. Attistitas molekularas metodes Anaplasmataceae dzimtas prokariotu prevalences noteikšanai erces (divpakapju PCR, hibridizacijas un sekvencešanas), ar hibridizacijas metodi noskaidrota Babesia gints sugu prevalence abu dzimumu erces un geografiska izplatiba Latvija. Tika noskaidrots, ka ercu encefalita incidences ikgadejie maksimumi 1994. un 1995. gada bija saistiti galvenokart tikai ar I. ricinus aktivitati šis ercu sugas izplatibas rajonos Latvija. I. ricinus un I. persulcatus ikgadejai aktivitatei monitoringa vietas noverota lidziga tendence (r=0,72; p<0,05), tomer atškiriga amplituda – kopš 1990. gada videjais ikgadejais I. ricinus imago skaits izmainijas seškartigi, kamer videjais ikgadejais I. persulcatus imago skaits tikai 3,6 reizes. Konstateta butiska virusa prevalences atškiriba daba savaktajam ercem un pacientiem nonemtajam ercem, attiecigi ap 1:10. Ikgadejai ercu encefalita incidencei (kopš 1973. gada) un ercu encefalita virusa prevalencei daba savaktajas abu dzimumu erces ir kopiga tendence (r=0,63; p<0,05). Butisku faktoru vidu, kas iespaido ikgadejo ercu aktivitates modeli, bija tieši videja lieluma ercu izbarotaju – jenotu, lapsu, zaku un vaveru skaita svarstibas, kuru ikgadejas skaita svarstibas uzradija ciešako saistibu ar imago un nimfu aktivitates tendencem (r=[0,52-0,81], p<0,05). Meteorologisko apstaklu saistiba ar Ixodes sugu attistibas stadiju aktivitati: vasaras-rudens temperaturu summa iepriekšeja gada, nokrišnu summa februari un aprila temperatura esošaja gada uzradija pozitivu korelaciju ar ikgadejam ercu aktivitates svarstibam (r=[0,49-0,65], p<0,05), savukart septembra nokrišnu summa – negativu korelaciju (r=[-0,50-(-0,54)], p<0,05). Ixodes sugas tika noteiktas morfologiski un attistita PCR metode Ixodes ercu morfologiski noteikto sugu molekularai parbaudei, pamatojoties uz ercu ITS2 gena fragmenta sugas specifiskam atškiribam. Apstiprinata 5’NCR-RT-PCR metodes jutiba un izmantošanas iespeja molekularai ercu encefalita virusa noteikšanai, lai gan nepieciešama tas talaka attistišana. B. burgdorferi s.l. prevalence erces, noteikta ar divpakapju PCR metodi 1999. – 2001. gada varieja no 18% lidz 38% I. ricinus imago, un no 25% lidz 51% I. persulcatus imago. Netika konstateta atškiriba Borrelia sp. prevalencei matites un tevinos, kas noradija uz iespejami atškirigu B. burgdorferi s.l. un ercu encefalita virusa transmisijas paraugu. Attistitas metodes Anaplasmataceae dzimtas prokariotu prevalences noteikšanai Ixodes ercu pulos (nested-PCR, hibridizacija un sekvencešana). Parbauditi 424 ercu puli, no kuriem 48 imago puli (11,3%) satureja Anaplasmataceae dzimtas prokariotus. Nimfu puliem netika konstatets pozitivs rezultats. 4% pulu tika konstateta A. phagocytophilum, 5,

The effect of chronic cigarette smoking on microvascular function, insulin resistance and inflammatory state

Cigarette smoking, a major risk factor for cardiovascular disease, can induce proinflammatory state and endothelial injury - the earliest manifestations of atherosclerotic changes. The aim of the study was to assess cutaneous vascular reactivity, insulin resistance and circulating levels of inflammatory cytokines in 20 healthy habitual smokers and 24 healthy non-smokers. The groups were matched for age. We used laser Doppler imaging with iontophoretic application of 1% acethylcholine solution and local heating 44 °C on the dorsum of the palm. Serum monocyte chemotactic protein-1, tumour necrosis factor-alpha and interleukin-6 were measured by xMAP technology. Insulin resdistance was assessed by HOMA-IR method. Local heating-induced neurally-mediated and endotheliumdependent vasodilatation was significantly decreased in elderly smokers vs. elderly non-smokers (p < 0.05). Young smokers showed significantly reduced endothelium-dependent vasodilatation vs. young non-smokers (p < 0.05). Ach-induced vasodilatation was significantly decreased in the elderly smokers and elderly non-smokers groups vs. young smokers and young non-smokers groups (p < 0.05). The level of tumour necrosis factor-alpha was significantly higher in both groups of smokers vs. non-smokers (p < 0.05). The level of monocyte chemotactic protein-1 was slightly higher in smokers. Only the elderly smokers group exhibited a tendency to higher values of HOMA-IR. Data showed that long-lasting cigarette smoking significantly impairs peripheral microvascular function due to increased inflammatory response.publishersversionPeer reviewe

Occurrence of Cryptosporidium spp. and Giardia spp. Infection in Humans in Latvia : Evidence of Underdiagnosed and Underreported Cases

Funding Information: Funding: This research was funded by the Fundamental and applied research “Transmission of Foodborne Parasitic pathogen from animals to humans: TRANSPAR” (lzp-2021/1-0055) and financed by the Ministry of Education and Science, Latvia. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Background and Objectives: Protozoan parasites—Cryptosporidium and Giardia—are important causes of diarrhea with an underestimated short-term burden on childhood growth and wellbeing in children under five years of age. The main transmission routes for both parasites are food and drinking water; transmission from person to person; and, due to their zoonotic nature, from domestic or wild animals to humans. The aims of the present study were to summarize the officially reported human cases of cryptosporidiosis and giardiasis in Latvia and to assess the occurrence of Cryptosporidium and Giardia in children within a prospective prevalence study. Materials and Methods: The number of officially reported cases of cryptosporidiosis and giardiasis in the time period of 2000–2020 was collected from the Centre for Disease Prevention and Control of Latvia. Data from a clinical diagnostic laboratory were included in the study in the period from 1 January 2008 to 31 December 2018. Additionally, a prospective study was performed, and fecal samples were collected from unique 0–17-year-old patients from January to February 2021 and tested using fluorescent microscopy. Results: Overall, during the 20-year period, 71 cases (mean per year = 9) of cryptosporidiosis and 1020 (mean per year = 34) cases of giardiasis were officially reported in Latvia. Meanwhile, within the prospective study, we found 35 (6.0%; 95%CI 4.3–8.1) Cryptosporidium and 42 (7.2%; 95%CI 5.3–9.6) Giardia cases. Conclusions: Here, we provide clear proof that both Cryptosporidium and Giardia are underdiagnosed in Latvia, which could also be true for neighboring Baltic and European countries, where a low number of cases are officially reported. Therefore, we highlight the hypothesis that the actual number of cryptosporidiosis and giardiasis human cases in the Baltic states is higher than that officially reported, including in Latvia.publishersversionPeer reviewe

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Centre for Genomic Pathogen Surveillance and the Euro-GASP study group: Sonja Pleininger, Alexander Indra, Irith De Baetselier, Wim Vanden Berghe, Blaženka Hunjak, Tatjana Nemeth Blažić, Panayiota Maikanti-Charalambous, Despo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Lasse Jessen Schwartz, Rita Peetso, Jevgenia Epstein, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Cécile Bébéar, Florence Lot, Susanne Buder, Klaus Jansen, Vivi Miriagou, Georgios Rigakos, Vasilios Raftopoulos, Eszter Balla, Mária Dudás, Lena Rós Ásmundsdóttir, Guðrún Sigmundsdóttir, Guðrún Svanborg Hauksdóttir, Thorolfur Gudnason, Aoife Colgan, Brendan Crowley, Sinéad Saab, Paola Stefanelli, Anna Carannante, Patrizia Parodi, Gatis Pakarna, Raina Nikiforova, Antra Bormane, Elina Dimina, Monique Perrin, Tamir Abdelrahman, Joël Mossong, Jean-Claude Schmit, Friedrich Mühlschlegel, Christopher Barbara, Francesca Mifsud, Alje Van Dam, Birgit Van Benthem, Maartje Visser, Ineke Linde, Hilde Kløvstad, Dominique Caugant, Beata Młynarczyk-Bonikowska, Jacinta Azevedo, Maria-José Borrego, Marina Lurdes Ramos Nascimento, Peter Pavlik, Irena Klavs, Andreja Murnik, Samo Jeverica, Tanja Kustec, Julio Vázquez Moreno, Asuncion Diaz, Raquel Abad, Inga Velicko, Magnus Unemo, Helen Fifer, Jill Shepherd, Lynsey PattersonBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.This study was supported by the European Centre for Disease Prevention and Control, the Centre for Genomic Pathogen Surveillance, the Li Ka Shing Foundation (Big Data Institute, University of Oxford), the Wellcome Genome Campus, the Foundation for Medical Research at Örebro University Hospital, and grants from Wellcome (098051 and 099202). LSB was funded by Conselleria de Sanitat Universal i Salut Pública, Generalitat Valenciana (Plan GenT CDEI-06/20-B), Valencia, Spain, and Ministry of Science, Innovation and Universities (PID2020–120113RA-I00), Spain, at the time of analysing and writing this manuscript.info:eu-repo/semantics/publishedVersio

Ixodes ricinus L. un Ixodes persulcatus P.Sch. (Acari: Ixodidae) izplatība, to pārnēsāto infekcijas slimību nozīme un molekulārā epidemioloģija Latvijā

Anotacija Ixodidae dzimtas erces ir pasaule pazistamas ka daudzveidigu cilveku un dzivnieku patogenu cirkulacijas uzturetajas daba. Musu valsti noverotas vairakas Ixodidae dzimtas sugas, tomer epidemiologiska nozime lidz šim konstateta tikai divam Ixodidae dzimtas Ixodes gints ercem: Ixodes ricinus L., kas izplatita visa valsts teritorija, retak tas austrumdala, kur domine Ixodes persulcatus P. Sch. Latvija tiek registreta iedzivotaju saslimstiba ar tris šo ercu parnesatam infekcijas slimibam - ercu encefalitu, Laima boreliozem un ari ar erlihiozi (anaplazmozi). Ši petijuma galvenais merkis bija noskaidrot Ixodidae epidemiologiski nozimigo ercu sugu izplatibu, to parnesato infekcijas slimibu nozimi un molekularo epidemiologiju Latvija. Šeit apkopoti un analizeti ilggadigi statistikas dati un kopš 1995. gada praktiski izdaritie noverojumi ercu parnesto slimibu dabas pereklos, to saistiba ar saslimstibas tendencem, veikta Ixodes ercu aktivitates un izplatibas ilggadigas tendences ietekmejušo faktoru izpete, ka ari apskatiti atsevišku Ixodes ercu parnesto patogeno un neskaidras patogenitates mikroorganismu sugu molekularie petijumi ar merki noskaidrot to izplatibu un sastopamibu Latvija. Attistitas molekularas metodes Anaplasmataceae dzimtas prokariotu prevalences noteikšanai erces (divpakapju PCR, hibridizacijas un sekvencešanas), ar hibridizacijas metodi noskaidrota Babesia gints sugu prevalence abu dzimumu erces un geografiska izplatiba Latvija. Tika noskaidrots, ka ercu encefalita incidences ikgadejie maksimumi 1994. un 1995. gada bija saistiti galvenokart tikai ar I. ricinus aktivitati šis ercu sugas izplatibas rajonos Latvija. I. ricinus un I. persulcatus ikgadejai aktivitatei monitoringa vietas noverota lidziga tendence (r=0,72; p<0,05), tomer atškiriga amplituda – kopš 1990. gada videjais ikgadejais I. ricinus imago skaits izmainijas seškartigi, kamer videjais ikgadejais I. persulcatus imago skaits tikai 3,6 reizes. Konstateta butiska virusa prevalences atškiriba daba savaktajam ercem un pacientiem nonemtajam ercem, attiecigi ap 1:10. Ikgadejai ercu encefalita incidencei (kopš 1973. gada) un ercu encefalita virusa prevalencei daba savaktajas abu dzimumu erces ir kopiga tendence (r=0,63; p<0,05). Butisku faktoru vidu, kas iespaido ikgadejo ercu aktivitates modeli, bija tieši videja lieluma ercu izbarotaju – jenotu, lapsu, zaku un vaveru skaita svarstibas, kuru ikgadejas skaita svarstibas uzradija ciešako saistibu ar imago un nimfu aktivitates tendencem (r=[0,52-0,81], p<0,05). Meteorologisko apstaklu saistiba ar Ixodes sugu attistibas stadiju aktivitati: vasaras-rudens temperaturu summa iepriekšeja gada, nokrišnu summa februari un aprila temperatura esošaja gada uzradija pozitivu korelaciju ar ikgadejam ercu aktivitates svarstibam (r=[0,49-0,65], p<0,05), savukart septembra nokrišnu summa – negativu korelaciju (r=[-0,50-(-0,54)], p<0,05). Ixodes sugas tika noteiktas morfologiski un attistita PCR metode Ixodes ercu morfologiski noteikto sugu molekularai parbaudei, pamatojoties uz ercu ITS2 gena fragmenta sugas specifiskam atškiribam. Apstiprinata 5’NCR-RT-PCR metodes jutiba un izmantošanas iespeja molekularai ercu encefalita virusa noteikšanai, lai gan nepieciešama tas talaka attistišana. B. burgdorferi s.l. prevalence erces, noteikta ar divpakapju PCR metodi 1999. – 2001. gada varieja no 18% lidz 38% I. ricinus imago, un no 25% lidz 51% I. persulcatus imago. Netika konstateta atškiriba Borrelia sp. prevalencei matites un tevinos, kas noradija uz iespejami atškirigu B. burgdorferi s.l. un ercu encefalita virusa transmisijas paraugu. Attistitas metodes Anaplasmataceae dzimtas prokariotu prevalences noteikšanai Ixodes ercu pulos (nested-PCR, hibridizacija un sekvencešana). Parbauditi 424 ercu puli, no kuriem 48 imago puli (11,3%) satureja Anaplasmataceae dzimtas prokariotus. Nimfu puliem netika konstatets pozitivs rezultats. 4% pulu tika konstateta A. phagocytophilum, 5,

Identification of Three Clinically Relevant Borrelia burgdorferi Sensu Lato Genospecies by PCR-Restriction Fragment Length Polymorphism Analysis of 16S-23S Ribosomal DNA Spacer Amplicons

We report the results of a study of the prevalences of three clinically relevant Borrelia burgdorferi sensu lato genospecies (Borrelia burgdorferi sensu stricto, Borrelia afzelii, and Borrelia garinii) in 1,040 questing Ixodes ticks from all regions of Latvia, where Lyme borreliosis is endemic. The prevalences of Borrelia in Ixodes ricinus and Ixodes persulcatus were 22.6 and 27.9%, respectively. Molecular typing of B. burgdorferi from infected ticks was performed by restriction fragment length polymorphism (RFLP) analysis of PCR-amplified fragments of the 16S-23S (rrs-rrlA) rRNA intergenic spacer by using species-specific primers and subsequent sequencing. The dominant Borrelia species in both Ixodes species was B. afzelii. In addition, different restriction patterns of B. garinii and B. afzelii were also identified. This study demonstrates that the 16S-23S rRNA PCR-RFLP typing method is simple, sensitive, and fast and that it allows one to differentiate among B. burgdorferi species and subspecies with various degrees of pathogenic potential directly in ticks. These features are important in monitoring Lyme disease

Prevalence of various Borrelia burgdorferi sensu lato Borrelia burgdorferi sensu lato Borrelia burgdorferi species in Ixodes ticks in three Baltic countries

Abstract Borrelia burgdorferi sensu lato, a tick-borne spirochete, is the causative agent of Lyme disease, the most prevalent vector-borne disease in Europe and United States. However, the incidence of this disease is variable and the clinical picture depends on the pathogen species. The infectivity of Ixodes ticks with Borrelia, was 46 % and 35 % in 2000 and 2001 in Latvia, respectively, and 14 % in 2002 in Lithuania, assessed by nested polymerase chain reaction (PCR) amplifi cation of the plasmid OspA gene fragment of Borrelia. PCR-restriction fragment length polymorphism (RFLP) analysis of the 16S-23S (rrs-rrlA) rRNA intergenic spacer was used for typing of Borrelia directly in ticks. Species-specifi c primers and subsequent sequences analysis were used as another approach for Borrelia species typing. All three clinically relevant B. burgdorferi sensu lato genospecies (B. afzelii, B. garinii, B. burgdorferi sensu stricto) were detected in the ticks collected in Latvia. The same result was obtained earlier in Estonia. B. valaisiana, a possible infectious agent of Lyme borreliosis, was detected only in Latvia. Only B. afzelii and B. garinii species were detected in ticks from Lithuania. Different subspecies were also identifi ed. This study demonstrates the predominance of the genospecies B. afzelii in all three Baltic countries, and the circulation of different B. burgdorferi sensu lato subspecies in the environment. This knowledge might have a signifi cant importance for monitoring of Lyme disease in Europe