6 research outputs found
Towards the Goal of Hepatitis C Elimination in Latvia ā Using Patient Survey Results
Get PDFThe success of global strategies to eliminate hepatitis C as a public threat by 2030 depends on local country-wide activities of all involved stakeholders, the most important being general practitioners (GP) and the entire country population. The opinion of currently diagnosed patients can help stakeholders to plan further actions such as addressing new target groups. Our aim was to determine the experiences, opinions, and attitudes of viral hepatitis C (VHC) patients towards the hepatitis C virus (HCV) infection and corresponding healthcare services in Latvia. Questionnaires were distributed by nurses in hospitals of major cities in Latvia. The survey results highlighted the importance of the role of the general practitioner and time from diagnosis to specialist consultation. The majority of respondents were not aware of VHC symptoms, although they were informed about possible complications such as liver cirrhosis and hepatocellular carcinoma. The major VHC patient pool was not composed of drug users, but people who never used narcotics, highlighting the importance to increase VHC awareness in other risk groups and in the general population. Consequently, targeted VHC screening programmes are essential tools in achieving elimination of HCV infection as a public threat in Latvia. The action plans should be updated regularly aiming to strengthening of the GP role and shortening time to consultation with a specialist.publishersversionPeer reviewe
Human leukocyte antigens class II alleles affecting the response to 5-7 year antiretroviral therapy in A Latvian cohort
Get PDFPublisher Copyright: Ā© 2019 Vladislavs Jasinskis et al., published by Sciendo 2019. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Antiretroviral therapy (ART) aims at suppressing viral replication and strengthening immune system in patients with HIV-1. Human Leukocyte Antigens (HLA) are among factors responsible for effectiveness of ART. The aim of this study was to determine the effect of HLA Class II alleles on the response to long-time ART, assessed by a change in CD4 + T-cell count in relation to viral load. The sample included 69 patients (17 females and 52 males) aged 20 to 50 with HIV-1 infection, who were undergoing ART in the Latvian Centre of Infectious Diseases. The median period of observation was 5.7 years. CD4 + T-cell count and viral load were analysed at the baseline and end of the period of observation. HLA typing was performed by polymerase chain reaction with low resolution sequence specific primers. Multiple hierarchical linear regression analysis confirmed that an increase in HIV-1 viral load was associated with a decrease in the level of CD4 + T-cell count. In addition, HLA-DRB1ā04 and HLA-DQB1ā06:01 alleles contributed negatively to the level of CD4 + T-cell count.Peer reviewe
The Immunogenetic Aspects of HIV-Associated Tuberculosis. Doctoral Thesis
No full textPromocijas darbs izstrÄdÄts: SIA RÄ«gas Austrumu klÄ«niskÄs universitÄtes slimnÄ«cas stacionÄrÄ āLatvijas InfektoloÄ£ijas centrsā. AizstÄvÄÅ”ana: 2017. gada 30. augustÄ plkst. 15.00 RÄ«gas StradiÅa universitÄtes MedicÄ«nas promocijas padomes atklÄtÄ sÄdÄ RÄ«gÄ, Dzirciema ielÄ 16, HipokrÄta auditorijÄ.Tuberkuloze ir infekcija, kas bieži attÄ«stÄs HIV-1 infekcijas gadÄ«jumÄ, vÄl vairÄk pastiprina imÅ«ndeficÄ«tu un veicina cilvÄka nÄvi. Par bÅ«tisku problÄmu ir atzÄ«ta novÄlota HIV asociÄtÄs tuberkulozes diagnostika, jo imÅ«ndeficÄ«ta stÄvoklÄ« mikobaktÄriju infekcijai zÅ«d tipiskie klÄ«niskie un rentgenoloÄ£iskie simptomi. LatvijÄ lÄ«dz ar HIV-1 infekcijas gadÄ«jumu skaita pieaugumu palielinÄs arÄ« HIV asociÄtas tuberkulozes gadÄ«jumu skaits. IepriekÅ”Äjie pÄtÄ«jumi parÄdÄ«ja, ka tuberkulozes attÄ«stÄ«bu HIV-1 infekcijas gadÄ«jumÄ ietekmÄ ne tikai HIV-1 vÄ«rusa aktivitÄte, bet arÄ« pacienta galvenÄ audu saderÄ«bas kompleksa II klases gÄnu (HLA II) uzbÅ«ves varianti un izmaiÅas imÅ«najÄ reakcijÄ. TajÄ paÅ”Ä laikÄ nav skaidrs, kÄds ir minÄto faktoru pienesums, kas varÄtu izskaidrot tuberkulozes pievienoÅ”anos pacientiem ar HIV-1 infekciju. TÄpÄc promocijas darba mÄrÄ·is bija izpÄtÄ«t HLA II klases gÄnu alÄļu saistÄ«bu ar imunoloÄ£iskÄ statusa rÄdÄ«tÄjiem un vÄ«rusa slodzi pacientiem ar HIV asociÄto tuberkulozi LatvijÄ. PÄtÄ«jums norisinÄjÄs RÄ«gas Austrumu klÄ«niskÄs universitÄtes slimnÄ«cas stacionÄrÄ āLatvijas InfektoloÄ£ijas centrsā laika periodÄ no 2012. gada lÄ«dz 2016. gadam. Paraugkopu veidoja 258 cilvÄki, no tiem 158 cilvÄki vecumÄ no 23 lÄ«dz 59 gadiem bija ar pierÄdÄ«tu HIV-1 infekciju un tuberkulozi (HIV-1/TB grupa) un 100 cilvÄki vecumÄ no 18 lÄ«dz 48 gadiem ar pierÄdÄ«tu HIV-1 infekciju bez tuberkulozes (HIV-1 grupa). Pacienti bija saÅÄmuÅ”i antiretrovirÄlo un prettuberkulozes terapiju atbilstoÅ”i Eiropas HIV-1 infekcijas diagnostikas, ÄrstÄÅ”anas un profilakses klÄ«niskajÄm vadlÄ«nijÄm. Tuberkulozes Ä£enÄtiskÄs predispozÄ«cijas izvÄrtÄÅ”anai tika veikta HLA II klases gÄnu (HLA-DRB1*, HLA-DQA1* un HLA-DQB1*) tipÄÅ”ana ar polimerÄzes Ä·Ädes reakcijas metodi reÄlÄ laika režīmÄ. Lai izvÄrtÄtu pacientu imunoloÄ£isko statusu, perifÄrajÄs asinÄ«s tika noteikts CD4+ Ŕūnu skaits, trÄ«s interleikÄ«nu (IL-1Ī², IL-10, IL-18) lÄ«menis un interferona-Ī³ (IFN-Ī³) lÄ«menis, HIV-1 infekcijas aktivitÄte tika izvÄrtÄta pÄc vÄ«rusa slodzes rÄdÄ«tÄja (HIV RNS). ImunoÄ£enÄtiskÄs analÄ«zes rezultÄtÄ tika identificÄtas 4 riska un 5 protektÄ«vÄs alÄles, kas ir saistÄ«tas ar HIV asociÄtÄs tuberkulozes attÄ«stÄ«bu. Tuberkuloze pacientiem ar HIV-1 infekciju ir asociÄta ar HLA-DQA1* gÄna 01:03, 05:01 alÄli, kÄ arÄ« ar HLA-DQB1* gÄna 02:01, 04:01 alÄli genotipÄ. SavukÄrt neuzÅÄmÄ«bu pret tuberkulozi ietekmÄ HLA-DRB1* gÄna 01 alÄle, HLA-DQA1* gÄna 01:01 un 01:02 alÄle, HLA-DQB1* gÄna 05:02 un 06:02 alÄle. Regresijas analÄ«ze ir parÄdÄ«jusi, ka no pÄtÄmajiem faktoriem, ar kuriem ir asociÄta tuberkulozes pievienoÅ”anÄs, galvenais faktors ir CD4+ T limfocÄ«tu skaits. KorelÄciju analÄ«ze rÄda, ka CD4+ Ŕūnu skaits ir saistÄ«ts ne tikai ar vÄ«rusa slodzi, kÄ tas bija parÄdÄ«ts iepriekÅ”Äjos pÄtÄ«jumos, bet arÄ« ar riska un protektÄ«vo alÄļu esamÄ«bu genotipÄ. SavukÄrt atklÄtÄ saistÄ«ba starp alÄlÄm, citokÄ«nu lÄ«meÅiem un CD4+ T limfocÄ«tu skaitu HIV asociÄtÄs tuberkulozes gadÄ«jumÄ apliecina alÄļu ietekmi uz organisma imunoloÄ£isko reakciju. AtseviŔķu HLA II klases gÄnu alÄļu efekts var izpausties, arÄ« ietekmÄjot tuberkulozes attÄ«stÄ«bas laiku. LÄ«dz ar iepriekÅ” zinÄmo sliktÄs prognozes rÄdÄ«tÄju, zemu CD4+ limfocÄ«tu skaitu, promocijas darbÄ saistÄ«bu ar exitus letalis uzrÄdÄ«ja arÄ« IL-18 lÄ«menis, kas miruÅ”iem pacientiem bija augstÄks nekÄ pacientiem, kuri konkrÄtajÄ laika ŔķÄrsgiezumÄ bija dzÄ«vi. KopumÄ iegÅ«tie rezultÄti sniedz detalizÄtÄku ieskatu Ä£enÄtisko faktoru lomÄ HIV asociÄtÄs tuberkulozes attÄ«stÄ«bÄ, kas var bÅ«t noderÄ«gs agrÄ«nÄ pacienta statusa novÄrtÄÅ”anÄ un terapijas nozÄ«mÄÅ”anÄ
The Immunogenetic Aspects of HIV-Associated Tuberculosis. Summary of the Doctoral Thesis
No full textPromocijas darbs izstrÄdÄts: SIA RÄ«gas Austrumu klÄ«niskÄs universitÄtes slimnÄ«cas stacionÄrÄ āLatvijas InfektoloÄ£ijas centrsā. AizstÄvÄÅ”ana: 2017. gada 30. augustÄ plkst. 15.00 RÄ«gas StradiÅa universitÄtes MedicÄ«nas promocijas padomes atklÄtÄ sÄdÄ RÄ«gÄ, Dzirciema ielÄ 16, HipokrÄta auditorijÄ.Tuberkuloze ir infekcija, kas bieži attÄ«stÄs HIV-1 infekcijas gadÄ«jumÄ, vÄl vairÄk pastiprina imÅ«ndeficÄ«tu un veicina cilvÄka nÄvi. Par bÅ«tisku problÄmu ir atzÄ«ta novÄlota HIV asociÄtÄs tuberkulozes diagnostika, jo imÅ«ndeficÄ«ta stÄvoklÄ« mikobaktÄriju infekcijai zÅ«d tipiskie klÄ«niskie un rentgenoloÄ£iskie simptomi. LatvijÄ lÄ«dz ar HIV-1 infekcijas gadÄ«jumu skaita pieaugumu palielinÄs arÄ« HIV asociÄtas tuberkulozes gadÄ«jumu skaits. IepriekÅ”Äjie pÄtÄ«jumi parÄdÄ«ja, ka tuberkulozes attÄ«stÄ«bu HIV-1 infekcijas gadÄ«jumÄ ietekmÄ ne tikai HIV-1 vÄ«rusa aktivitÄte, bet arÄ« pacienta galvenÄ audu saderÄ«bas kompleksa II klases gÄnu (HLA II) uzbÅ«ves varianti un izmaiÅas imÅ«najÄ reakcijÄ. TajÄ paÅ”Ä laikÄ nav skaidrs, kÄds ir minÄto faktoru pienesums, kas varÄtu izskaidrot tuberkulozes pievienoÅ”anos pacientiem ar HIV-1 infekciju. TÄpÄc promocijas darba mÄrÄ·is bija izpÄtÄ«t HLA II klases gÄnu alÄļu saistÄ«bu ar imunoloÄ£iskÄ statusa rÄdÄ«tÄjiem un vÄ«rusa slodzi pacientiem ar HIV asociÄto tuberkulozi LatvijÄ. PÄtÄ«jums norisinÄjÄs RÄ«gas Austrumu klÄ«niskÄs universitÄtes slimnÄ«cas stacionÄrÄ āLatvijas InfektoloÄ£ijas centrsā laika periodÄ no 2012. gada lÄ«dz 2016. gadam. Paraugkopu veidoja 258 cilvÄki, no tiem 158 cilvÄki vecumÄ no 23 lÄ«dz 59 gadiem bija ar pierÄdÄ«tu HIV-1 infekciju un tuberkulozi (HIV-1/TB grupa) un 100 cilvÄki vecumÄ no 18 lÄ«dz 48 gadiem ar pierÄdÄ«tu HIV-1 infekciju bez tuberkulozes (HIV-1 grupa). Pacienti bija saÅÄmuÅ”i antiretrovirÄlo un prettuberkulozes terapiju atbilstoÅ”i Eiropas HIV-1 infekcijas diagnostikas, ÄrstÄÅ”anas un profilakses klÄ«niskajÄm vadlÄ«nijÄm. Tuberkulozes Ä£enÄtiskÄs predispozÄ«cijas izvÄrtÄÅ”anai tika veikta HLA II klases gÄnu (HLA-DRB1*, HLA-DQA1* un HLA-DQB1*) tipÄÅ”ana ar polimerÄzes Ä·Ädes reakcijas metodi reÄlÄ laika režīmÄ. Lai izvÄrtÄtu pacientu imunoloÄ£isko statusu, perifÄrajÄs asinÄ«s tika noteikts CD4+ Ŕūnu skaits, trÄ«s interleikÄ«nu (IL-1Ī², IL-10, IL-18) lÄ«menis un interferona-Ī³ (IFN-Ī³) lÄ«menis, HIV-1 infekcijas aktivitÄte tika izvÄrtÄta pÄc vÄ«rusa slodzes rÄdÄ«tÄja (HIV RNS). ImunoÄ£enÄtiskÄs analÄ«zes rezultÄtÄ tika identificÄtas 4 riska un 5 protektÄ«vÄs alÄles, kas ir saistÄ«tas ar HIV asociÄtÄs tuberkulozes attÄ«stÄ«bu. Tuberkuloze pacientiem ar HIV-1 infekciju ir asociÄta ar HLA-DQA1* gÄna 01:03, 05:01 alÄli, kÄ arÄ« ar HLA-DQB1* gÄna 02:01, 04:01 alÄli genotipÄ. SavukÄrt neuzÅÄmÄ«bu pret tuberkulozi ietekmÄ HLA-DRB1* gÄna 01 alÄle, HLA-DQA1* gÄna 01:01 un 01:02 alÄle, HLA-DQB1* gÄna 05:02 un 06:02 alÄle. Regresijas analÄ«ze ir parÄdÄ«jusi, ka no pÄtÄmajiem faktoriem, ar kuriem ir asociÄta tuberkulozes pievienoÅ”anÄs, galvenais faktors ir CD4+ T limfocÄ«tu skaits. KorelÄciju analÄ«ze rÄda, ka CD4+ Ŕūnu skaits ir saistÄ«ts ne tikai ar vÄ«rusa slodzi, kÄ tas bija parÄdÄ«ts iepriekÅ”Äjos pÄtÄ«jumos, bet arÄ« ar riska un protektÄ«vo alÄļu esamÄ«bu genotipÄ. SavukÄrt atklÄtÄ saistÄ«ba starp alÄlÄm, citokÄ«nu lÄ«meÅiem un CD4+ T limfocÄ«tu skaitu HIV asociÄtÄs tuberkulozes gadÄ«jumÄ apliecina alÄļu ietekmi uz organisma imunoloÄ£isko reakciju. AtseviŔķu HLA II klases gÄnu alÄļu efekts var izpausties, arÄ« ietekmÄjot tuberkulozes attÄ«stÄ«bas laiku. LÄ«dz ar iepriekÅ” zinÄmo sliktÄs prognozes rÄdÄ«tÄju, zemu CD4+ limfocÄ«tu skaitu, promocijas darbÄ saistÄ«bu ar exitus letalis uzrÄdÄ«ja arÄ« IL-18 lÄ«menis, kas miruÅ”iem pacientiem bija augstÄks nekÄ pacientiem, kuri konkrÄtajÄ laika ŔķÄrsgiezumÄ bija dzÄ«vi. KopumÄ iegÅ«tie rezultÄti sniedz detalizÄtÄku ieskatu Ä£enÄtisko faktoru lomÄ HIV asociÄtÄs tuberkulozes attÄ«stÄ«bÄ, kas var bÅ«t noderÄ«gs agrÄ«nÄ pacienta statusa novÄrtÄÅ”anÄ un terapijas nozÄ«mÄÅ”anÄ
HIV asociÄtÄs tuberkulozes imunoÄ£enÄtiskie aspekti. Promocijas darba kopsavilkums
No full textThe dissertation was written in the Latvian Centre of Infectious Diseases of Riga Eastern Clinical University Hospital. Defence: on the 30th of August, 2017 at 15.00 at an open meeting of Promotion Council of Medicine of RÄ«ga StradiÅÅ” University at the Hippocrates Lecture Theatre, in Dzirciema Street 16, Riga.Tuberculosis is an infectious disease, which develops frequently during HIV-1 infection and increases immunodeficiency accelerating oneās death. Diagnostics of HIV-associated tuberculosis is an important problem, because of losing typical clinical and roentgenological symptoms of the mycobacterial infection under pronounced immunodeficiency. In Latvia, the number of patients with HIV-associated tuberculosis increased simultaneously with increasing number of patients with HIV-1. Previous studies demonstrated that development of tuberculosis in patients with HIV-1 is impacted not only by HIV-1 virus activity but also by allelic variants of genesā class II of the major histocompatibility complex and by change in an immune reaction. At the same time, there is no clarity regarding the contribution of each factor explaining development of tuberculosis in patients with HIV-1 infection. Therefore, the aim of the doctoral thesis (The Immunogenetic aspects of HIV-associated tuberculosis) was to investigate the relationship of HLA Class II alleles with markers of immunological status and HIV-1 viral load in patients with HIV-associated tuberculosis in Latvia. The research was performed in Riga East University Hospital, Latvian Centre of Infectious Disease between 2012 and 2016. The research sample consisted of 258 patients. The first group included 158 HIV-associated tuberculosis patients at age from 23 to 59 with HIV-1 infection and confirmed active tuberculosis (HIV-1/TB group). The second group included 100 patients at age from 18 to 48 with HIV-1 infection without tuberculosis (HIV-1 group). All patients with HIV-1 infection and tuberculosis received antiretroviral therapy and anti-tuberculosis therapy according to Guidelines for treatment of HIV-1 infected adults in Europe. In order to assess genetic predisposition, HLA class II (HLA-DRB1*, HLA-DQA1*, and HLA-DQB1*) typing was performed by real time polymerase chain reaction. In order to assess immunological status, CD4+ cells count, levels of three interleukins (IL-1Ī², IL-10, IL-18) and of interferon-Ī³ (IFN-Ī³) were detected in peripheral blood. HIV-1 viral activity was represented by viral load (HIV RNS). The results of immunogenetic analysis revealed five protective and four risk alleles associated with development of HIV-associated tuberculosis. In patients with HIV-1, development of tuberculosis associates with HLA-DQA1*01:03, HLA-DQA1*05:01, HLA-DQB1*02:01, and HLA-DQB1*04:01 alleles. Resistance against tuberculosis associates with HLA-DRB1*01, HLA-DQA1*01:01, HLA-DQA1*01:02, HLA-DQB1*05:02, and HLA-DQB1*06:02 alleles. The results of a regression analysis demonstrate that the number of CD4+ T lymphocytes is the main factor associated with the development of tuberculosis coinfection among factors included into analysis. A correlative analysis indicate that the number of CD4+ cells is related to viral load that is in accordance with the previous studies. In addition, the number of CD4+ cells correlates with risk and protectives alleles. Within a group of HIV-associated tuberculosis, correlations between alleles, levels of cytokines, and the number of CD4+ T lymphocytes confirm an impact of alleles on immunological reaction. Some alleles of HLA class II can have an effect on time of tuberculosis development. In addition to revealed effect of CD4+ T lymphocytes, this study revealed the relationship between exitus letalis and the level of IL-18 (higher in the group of patients who were alive in a certain time point). In summary, the results provide more detailed view of genetic factors in the development of HIV-associated tuberculosis. The findings can be also helpful in the early assessment of the patientās status and assigning a therapy
