Immunoloogiliste faktorite mõju HIV-i, B-hepatiidi ja C-hepatiidi viirustesse nakatumisele süstivate narkomaanide hulgas

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Inimese immuunpuudulikkuse viirus (HIV), B-hepatiidi viirus (HBV) ja C-hepatiidi viirus (HCV) põhjustavad nii maailmas kui ka Eestis mitmeid terviseprobleeme. Nende viiruste nakatumisteed on sarnased ja seega on sagedane samaaegne haigestumine nii HIV kui ka hepatiidi viirustega. Eriti suur on probleem süstivate narkomaanide (SN) seas. Kuigi süstimise teel levivad HIV, HBV ja HCV väga efektiivselt, on mitmeid inimesi, kes nende viirustega ei nakatu (eksponeeritud seronegatiivsed inimesed – ESN). Siiani ei ole teada nende mitte-nakatumise põhjuseid, kuid vastavate mehhanismide väljaselgitamine võib aidata võidelda viirusnakkuste levikuga või hõlbustada uute ravimite välja töötamist. Varasemad uuringud seksuaalsel teel eksponeeritute seas on näidanud, et HIV-i nakatumist mõjutavad ka inimese geneetilised ja immunoloogilised faktorid, sealhulgas T rakkude hulk ning jaotus. Käesoleva töö eesmärgiks oli kirjeldada, kuidas T rakkude jaotus ja interleukiin 10 (IL-10) polümorfismid mõjutavad HIV-i nakatumist ja kuidas HIV-i koosesinemine HBV ja HCV-ga ning süstiv narkomaania mõjutavad T rakkude jaotust SN-idel. Uuringusse kaasati 345 SN-i ja 496 veredoonorit ning T rakkude analüüsiks lisaks 45 vanusele ja soole kohandatud tervet vabatahtlikku. Interleukiin 10 (IL-10) polümorfismid määrati reaalaja PCR-iga ning T rakkude analüüs teostati voolutsütomeetriga. Uuringus leiti, et IL-10 –1082A ja –592A alleelid kaitsevad HIV nakkuse eest ja –592AC-d sisaldavad genotüübi paarid kaitsevad HIV ning HBV nakkuste eest SN-ide seas. Sarnaselt seksuaalsel teel nakatunud ESN-idele, on narkootikume süstivatel ESN-idel kõrgem immuunaktivatsioon, kõrgem CD45RA+RO+ rakkude protsent ja madalam CCR5 ekspresioon kui tevetel vabatahtlikel. HBV+HCV+ kaksiknakkusega SN-idel on muutunud ainult CD4+ rakkude arvukus, mis näitab, et HBV ja/või HCV seropositiivsus omab vähest mõju T raku jaotusele. HIV–HBV–HCV– SN-idel on muutunud mälurakude jaotus, kõrgem immuunaktivatsioon ja rohkem CCR5+ rakke võrreldes tervete vabatahtlikega. Seega mõjutab ka süstiv narkomaania HIV-st, HBV-st ja HCV-st sõltumata T rakkude jaotust.Intravenous drug use is one of the most important transmission routes for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Despite repeated exposure some individuals remain uninfected (exposed seronegative individuals –ESN). The reasons for remaining seronegative are not yet fully understood. The protection against HIV, HBV, and HCV has been associated with multiple genetic polymorphisms and immunological factors such as T cell distribution. However, majority of studies have been conducted in sexually exposed subjects and data regarding persons who inject drugs (PWID) is limited. We aimed to describe whether IL-10 polymorphisms influence HIV, HBV, and HCV susceptibility and how exposure and seropositivity to these viruses influence T cell distribution among Caucasian PWID. A total of 345 PWID, 496 blood donors, and 47 healthy volunteers were recruited. The IL-10 –592C/A and –1082A/G polymorphisms were determined using Real-Time PCR and T cell distribution using multicolor flow cytometry. We found, that the presence of low IL-10 producing alleles –1082A and –592A protects highly exposed PWID against HIV and HBV infections. In terms of T cell distribution, similarly to sexually exposed ESN, individuals with parenteral exposure have increased immune activation, increased percentages of CD45RA+RO+ cells and lower CCR5 expression on CD4+ cells compared to healthy volunteers. The T cell distribution among triple infected individuals HIV+HBV+HCV+ was similar to the one seen in previous studies among HIV mono-infected individuals (lower percentages of CD4+ and increased immune activation) and therefore probably triggered by the HIV infection. HBV and/or HCV co-infections had a minimal effect to these changes. Additionally to HIV, HBV/HCV double-infection influenced only the percentages of CD4+ T cells and the seropositivity to these viruses has a minimal effect to T cell distribution. Whereas intravenous drug use appeared to influence T cell distribution towards immune activation and increase in HIV co-receptor CCR5 expression

Noroviiruse tüved Eestis 2015–2016 ägeda gastroenteriidiga hospitaliseeritud lastel vanuses 0–18 aastat

Eesti Arst 2022; 101(9):50

Acute gastroenteritis hospitalizations after implementation of universal mass vaccination against rotavirus

Eesti Arst 2020; 99(7):44

Stable level of HIV transmitted drug resistance in Estonia despite significant scale-up of antiretroviral therapy

BACKGROUND: Due to the widespread use of non-nucleoside reverse transcriptase inhibitors (NNRTI) as part of first-line therapies to curb the human immunodeficiency virus (HIV) epidemic in Eastern-European countries, transmitted drug resistance (TDR) is of serious concern in this region. Therefore, TDR and its associated risk factors were investigated among newly diagnosed HIV-1 subjects in Estonia. METHODS: This nationwide observational study included all newly diagnosed HIV-1 subjects from January 1 until December 31, 2013. Demographic and clinical data were collected using the national surveillance system and the Estonian HIV-positive patient database (E-HIV). Starting from RNA, the HIV-1 protease (PR) and reverse transcriptase (RT) region was sequenced and surveillance drug resistance mutations (SDRM) were determined. Sequences from previous studies in Estonia and from public databases were included to study epidemic trends and to determine TDR clusters by phylogenetic analysis. RESULTS: Out of 325 newly diagnosed HIV-1 infections, 224 were successfully sequenced (68%). As in previous studies from Estonia, the circulating recombinant form CRF06_cpx was the most prevalent HIV subtype (164/224, 74%). Fifteen strains displayed SDRM, giving a TDR rate of 6.7% (95% CI 3.9; 11.0). The most common SDRMs were associated with NNRTI (10/15, 4.5%), followed by PI (3/15, 1.3%) and NRTI (2/15, 0.9%). K103 N (8/15, 53%) was the most common SDRM. The level of TDR and mutational patterns were comparable to previous years. Twenty-six transmission clusters containing Estonian sequences were observed, of which 23/26 belonged to CRF06_cpx and 2/26 displayed evidence of TDR. The only risk factor associated with the presence of TDR was imprisonment (OR 5.187, CI 1.139-25.565, p = 0.034). CONCLUSIONS: TDR remained stable at a moderate level in Estonia, K103N is the main SDRM with only one transmission-pair detected. We suggest screening for TDR at the time of diagnosis or prior to antiretroviral treatment initiation to tailor first-line regimens accordingly. SUMMARY: The third consecutive transmitted drug resistance (TDR) study demonstrated a stable TDR in Estonia. TDR reached 6.7% (moderate level) in 2013, with imprisonment being the only associated risk factor. Few drug resistance-associated transmission clusters were identified.status: publishe

A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.

The role of CC chemokine receptor 5 (CCR5) and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID) from Estonia.Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four CCL5 haplotypes (A-D) were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789) typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis.Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C) decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40), which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29). An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively) compared to those who did not possess these haplotypes, respectively.Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV