Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19.

Introduction: Pathogenic mechanisms and long-term consequences of COVID-19 require attention in studies on SARS-CoV-2. The association of the severity of COVID-19 with genetic factors, such as human leukocyte antigen (HLA) genes, remains underexplored. Our study assessed the relationships between HLA class II alleles and COVID-19 severity and blood-based indicators of systemic inflammation and organ damage, serum markers of epithelial cell apoptosis such as caspase-cleaved CK18 fragment M30 (CK18-M30) and the extracellular matrix product hyaluronic acid (HA). Material and methods: The study included 101 hospitalized COVID-19 patients (mean age 60 ±14 years). Clinical tests were performed at admission to the hospital. The levels of CK18-M30 and HA were detected in serum by enzyme-linked immunosorbent assay (ELISA). HLA typing was performed in HLA-DRB1, -DQA1, and -DQB1 loci by the polymerase chain reaction with low-resolution sequence-specific primers. Results: Sixty-one patients had a non-severe and 40 had a severe or critical disease course (following the WHO definition). The severity was associated with older age, male gender, higher HA, CK18-M30, and some indicators of inflammation. Despite the lack of direct association between HLA alleles and the severity of COVID-19, the presence of HLA-DRB1*04 and 12 alleles in the genotype was associated with lowered or elevated HA, respectively. The HLA-DQB1*03:01 allele was associated with lowered CK18-M30, aspartate aminotransferase, and ferritin. In addition, HLA-DQB1*06:01 was associated with elevated alanine aminotransferase. Conclusions: Associations of HLA class II alleles with markers of epithelial cell apoptosis and extracellular matrix production indirectly support the influence of HLA genes on acute COVID-19 severity.

Gut-Lung Microbiota Interaction in COPD Patients: A Literature Review.

Respiratory diseases are one of the leading causes of death in the world, which is why a lot of attention has been recently paid to studying the possible mechanisms for the development of pulmonary diseases and assessing the impact on their course. The microbiota plays an important role in these processes and influences the functionality of the human immune system. Thus, alterations in the normal microflora contribute to a reduction in immunity and a more severe course of diseases. In this review, we summarized the information about gut and lung microbiota interactions with particular attention to their influence on the course of chronic obstructive pulmonary disease (COPD).

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

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.

Seroprevalence of diphtheria and measles antibodies and their association with demographics, self-reported immunity, and immunogenetic factors in healthcare workers in Latvia.

Latvia is among European countries with outbreaks of diphtheria and measles. Healthcare workers (HCW) are exposed to infections and can transmit them to unvaccinated patients. We assessed the seroprevalence of antibodies against diphtheria and measles and their association with demographics, self-reported immunity, the presence of the HLA-B27 allele, and level of interferon regulatory factor 5 (IRF5) in Latvian HCW. Anti-diphtheria and anti-measles IgG antibodies and the level of IRF5 in serum were tested by enzyme immunoassay. The presence of the HLA-B27 allele was detected by a real-time polymerase chain reaction. The study involved 176 HCW, including 29% doctors and 44% nurses. Among HCW, 95.5% were seropositive for diphtheria. However, only 65.9% had full seroprotection against it. The seronegativity for measles (21.6%) was higher than for diphtheria (4.5%) without differences in gender and medical staff groups. Older age was associated with waning immunity against diphtheria and a higher rate of seropositivity for measles. Considered immunogenetic factors did not affect the level of antibodies, and variability of the level of IRF5 in serum can reflect ageing processes. Self-reported vaccination status had a low informative value regarding full seroprotection against diphtheria and seropositivity for measles indicating the need for pre-vaccination IgG screening in planning the booster vaccination.

Post-COVID-19 Liver Injury: Comprehensive Imaging With Multiparametric Ultrasound.

OBJECTIVES: This study aimed to define patterns of liver injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using multiparametric ultrasound (mpUS) in a variable patient population with differing severities of COVID-19. METHODS: Ninety patients were enrolled into the study: 56 had SARS-CoV-2 3-9 months prior to enrolment; 34 served as a clinically healthy control group. All patients underwent an mpUS evaluation of the liver (elastography, dispersion and attenuation imaging). Seventy-six patients had abdominal magnetic resonance (MR) and noncontrast enhanced thoracic computed tomography (CT) scans performed at the same day. All patients were screened for biochemical markers of liver injury. RESULTS: Liver elasticity, viscosity, and steatosis values were significantly altered in patients after COVID-19, with particularly higher fibrosis scores compared to the control group (P < .001). Increased biochemical markers of liver injury correlated with changes in mpUS (P < .05), but not with findings on CT or MR findings. Seventeen of 34 hospitalized patients had a moderate or severe course of the disease course with more pronounced changes in mpUS. Increased body mass index was found to influence liver injury and correlated with more severe forms of COVID-19 (P < .001). CONCLUSIONS: COVID-19 can cause liver injury observable using mpUS. More severe forms of COVID-19 and patient obesity are related to increased values of liver damage observed. In comparison to MRI and CT, mpUS appears to be more sensitive to involvement of liver parenchyma. Further research is warranted to establish this promising method for evaluating post-COVID-19 liver involvement in the aftermath of the pandemic.

Amino Acid Metabolism is Significantly Altered at the Time of Admission in Hospital for Severe COVID-19 Patients: Findings from Longitudinal Targeted Metabolomics Analysis.

The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we suggest that glutamine deprivation may further result in inhibited M2 macrophage polarization as a complementary process, and highlight the contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application. IMPORTANCE Although the host defense mechanisms against SARS-CoV-2 infection are still poorly described, they are of central importance in shaping the course of the disease and the possible outcome. Metabolomic profiling may complement the lacking knowledge of the molecular mechanisms underlying clinical manifestations and pathogenesis of COVID-19. Moreover, early identification of metabolomics-based biomarker signatures is proved to serve as an effective approach for the prediction of disease outcome. Here we provide the list of metabolites describing the severe, acute phase of the infection and bring the evidence of crucial metabolic pathways linked to aggressive immune responses. Finally, we suggest metabolomic phenotyping as a promising method for developing personalized care strategies in COVID-19 patients.

Invasive Pneumococcal Disease in Latvia in PCV10 Vaccination Era, 2012-2018.

In 2010 in Latvia, invasive pneumococcal disease (IPD) became a cause for concern and vaccination of infants with four doses of 7-valent pneumococcal conjugate vaccine (PCV7) commenced. In 2012, 10-valent pneumococcal conjugate vaccine (PCV10) (three doses at 2, 4, and 12-15 month of age) vaccination was introduced. We described incidence and serotype distribution of IPD in Latvia and investigated serotypes associated with death from IPD based on surveillance data. Adult vaccination against pneumococcal infection is not included in the national immunization program. Laboratory confirmed IPD cases are passively notified to the Center for Disease Prevention and Control of Latvia (CDPC) by laboratories and clinicians. We calculated incidence by age, sex, case fatality, and trend in serotypes by conducting a retrospective population-based cross-sectional study based on national IPD surveillance data. From 2012 to 2018 466 cases of IPD were reported. The highest notified incidence was in 2015 at 4.4/100,000, which fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in the elderly (6.0). PCV10 vaccine serotypes were the most prevalent in IPD cases up to 2015 with a decreasing trend from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend of odds = 0.000). PCV23nonPCV13 vaccine serotypes had an increasing trend and rose from 18% (7/40) to 34% (25/74) (chi2 test for trend of odds = 0.000). Non-Vaccine serotypes had an increasing trend and rose from 13% (5/40) to 27% (20/74) (chi2 test for trend of odds = 0.038). Reported total case fatality was 19% (87/466). The highest, at 36% (20/56), was reported in 2013. After adjusting for age, Streptococcus pneumoniae serotype 3 was associated with death from IPD (adjusted OR 2.3 95%CI 1.25-4.12 p 0.007). Surveillance data indicate evidence of serotype replacement with an increasing trend of serotype 19A and PPV23nonPCV13 and Non-Vaccine serotypes. Serotype 3 and age were associated with fatal IPD outcome. Further studies of S. pneumoniae carriage would be useful in providing more evidence to characterize serotypes' circulation.

Intriguing findings of liver fibrosis following COVID-19.

BACKGROUND: Studies on a new coronavirus disease (COVID-19) show the elevation of liver enzymes and liver fibrosis index (FIB-4) independently on pre-existing liver diseases. It points to increased liver fibrogenesis during acute COVID-19 with possible long-term consequences. This study aimed to assess liver fibrosis in COVID-19 patients by serum hyaluronic acid (HA) and FIB-4. METHODS: The study included the acute COVID-19 group (66 patients, 50% females, mean age 58.3 ± 14.6), the post-COVID group (58 patients in 3-6 months after the recovery, 47% females, mean age 41.2 ± 13.4), and a control group (17 people, 47% females, mean age 42.8 ± 11.0). Ultrasound elastography was performed in the post-COVID and control groups. RESULTS: Sixty-five percent of the acute COVID-19 group had increased FIB-4 (> 1.45), and 38% of patients had FIB-4 ≥ 3.25. After matching by demographics, 52% of acute COVID-19 and 5% of the post-COVID group had FIB-4 > 1.45, and 29% and 2% of patients had FIB-4 ≥ 3.25, respectively. Increased serum HA (≥ 75 ng/ml) was observed in 54% of the acute COVID-19 and 15% of the post-COVID group. In the acute COVID-19 group, HA positively correlated with FIB-4, AST, ALT, LDH, IL-6, and ferritin and negatively with blood oxygen saturation. In the post-COVID group, HA did not correlate with FIB-4, but it was positively associated with higher liver stiffness and ALT. CONCLUSION: More than half of acute COVID-19 patients had increased serum HA and FIB-4 related to liver function tests, inflammatory markers, and blood oxygen saturation. It provides evidence for the induction of liver fibrosis by multiple factors during acute COVID-19. Findings also indicate possible liver fibrosis in about 5% of the post-COVID group.

Electrocardiographic Abnormalities and Mortality in Epilepsy Patients.

Background and Objectives: People with epilepsy (PWE) have a 2-3 times higher mortality rate than the general population. Sudden unexpected death in epilepsy (SUDEP) comprises a significant proportion of premature deaths, whereas sudden cardiac death (SCD) is among the leading causes of sudden death in the general population. Cardiac pathologies are significantly more prevalent in PWE. Whether electrocardiographic (ECG) parameters are associated with remote death in PWE has yet to be elucidated. The study objective was to assess whether interictal ECG parameters are associated with mortality in the long-term. Materials and Methods: The study involved 471 epilepsy patients who were hospitalized after a bilateral tonic-clonic seizure(s). ECG parameters were obtained on the day of hospitalization (heart rate, PQ interval, QRS complex, QT interval, heart rate corrected QT interval (QTc), ST segment and T wave changes), as well as reported ECG abnormalities. Mortality data were obtained from the Latvian National Cause-of-Death database 3-11, mean 7.0 years after hospitalization. The association between the ECG parameters and the long-term clinical outcome were examined. Results: At the time of assessment, 75.4% of patients were alive and 24.6% were deceased. Short QTc interval (odds ratio (OR) 4.780; 95% confidence interval (CI) 1.668-13.698; p = 0.004) was associated with a remote death. After the exclusion of known comorbidities with high mortality rates, short QTc (OR 4.631) and ECG signs of left ventricular hypertrophy (OR 5.009) were associated with a remote death. Conclusions: The association between routine 12-lead rest ECG parameters-short QTc interval and a pattern of left ventricular hypertrophy-and remote death in epilepsy patients was found. To the best of our knowledge, this is the first study to associate rest ECG parameters with remote death in an epileptic population.

Analysis of Mycobacterium tuberculosis genetic lineages circulating in Riga and Riga region, Latvia, isolated between 2008 and 2012.

Although the number of new tuberculosis (TB) cases registered per year has decreased by 3-fold between 2001 and 2017 in Latvia, the TB incidence and rates of multidrug resistant TB in this Baltic country remain substantially higher than in most other European countries. Molecular typing methods of Mycobacterium tuberculosis (MTB) play an important role both in clinical studies of the disease and the epidemiological investigations, allowing to describe and characterize the pathogen's population structure and spread of particular genotypes. Aim of this study was to examine the prevalence of MTB lineages in Riga and Riga region of Latvia within a five-year period (2008-2012), and to evaluate the discriminatory power (DP) of spoligotyping, standard 24-locus MIRU-VNTR and IS6110-RFLP methods in this setting. The results showed that the main MTB spoligotype families were Beijing (25.3%) and LAM (24.3%), followed by T (22.1%), Ural (11.2%), Haarlem (6.6%) and X superfamily (3.4%). This distribution remained stable over the five consecutive years. 67.6% of MTB isolates were pan-susceptible, and 32.4% were resistant to any drug; multi-drug resistance was found in 5.8% of MTB strains, and 7.6% of MTB isolates were extensively drug-resistant. Drug resistance was associated with SIT1, SIT283 and SIT42 genotypes, while SIT1 and SIT42 were overrepresented among multi drug-resistant MTB strains. Overall, DP of spoligotyping method alone was 0.8953, while DP of both 24-locus MIRU-VNTR analysis and IS6110 RFLP was higher (DP = 0.9846 and 0.9927, respectively), mainly due to the improvement of the resolution for the Beijing strains. In conclusion, this work represents the first comprehensive molecular epidemiological description of TB in Latvia, highlighting the high genetic diversity of MTB strains circulating in Riga and Riga region. In combination with detailed epidemiological data this approach was helpful for the in-depth understanding of epidemiological processes in settings where the Next-Gen sequencing is not available as a routine method.

Ultrasound-Assisted Lumbar Interlaminar Epidural Dye Injection and Evaluation of Its Distribution by Anatomical Dissection.

Background: Epidural steroid injections are frequently used to treat lumbar radicular pain. However, the spread of a solute in the epidural space needs further elucidation. We aimed at assessing the distribution of green dye in the epidural space after lumbar epidural injection on cadavers. Methods: We performed ultrasound-guided injections of green dye between lumbar vertebrae 4 and 5 in 24 cadavers. The cadavers were randomly divided into group A and B according to the volume of injected dye; 3 ml in group A (n = 13) and 6 ml in group B (n = 11). Accuracy of the needle insertion and patterns and distributions of the spread were compared between the groups. After local dissection, we examined the spread of dye in dorsal and ventral epidural spaces and presented the distribution as whole numbers and quartiles of intervertebral segments. Mann-Whitney U Test was used to compare distribution of dye spread between groups A and B. Wilcoxon Signed-Rank Test was used to compare the spread of dye in cranial and caudal direction within the group. We considered P < 0.05 as significant. Results: Data were obtained from all 24 cadavers. Median levels of dorsal cranial dye distribution in groups A and B were 2 and 4 (P = 0.02), respectively. In the dorsal caudal-2 and 2, respectively (P = 0.04). In the ventral epidural space cranial dye spread medians were-0 and 2 in groups, respectively (P = 0.04). Ventral caudal spread was 0 and 1, respectively (P = 0.03). We found a significant difference between cranial and caudal dye distribution in group B (P < 0.05). In group A the dye spread was bilateral. In group B cranial and caudal dye spread was observed. Conclusions: Ventral dye flow was observed in 50% of injections. Bilateral spread of dye occurred in 63%, and more often in group A. Cranial spread was slightly higher than caudal spread in group A despite a smaller injected volume, and significantly higher in group B following a larger volume.

Risk Factors for Human Cystic Echinococcosis in Latvia.

Despite the importance of Echinococcus spp. in the Baltic States, little is known about the locally relevant risk factors for contracting the human disease they can cause. The aim of this study was to compare the frequency of selected potential risk factors in individuals diagnosed with cystic echinococcosis (CE) in 1999-2015 and matched controls. The diagnoses of the cases were based on combination of serology and diagnostic imaging, and they were not confirmed to species level of the causative parasite. A total of 46 cases and 46 control individuals were included in the study and answered questions covering a selection of potential risk factors for CE. Living in rural dwelling, owning dogs kept or roaming outdoors, owning dogs fed with viscera of livestock, having close contact with dogs or cats, owning livestock, home slaughtering, and having hunters in the family were significantly more common among the cases than the controls. The identified risk factors can inform planning preventive measures, but species/strain-level diagnoses of human echinococcosis would help in targeting the preventive measures more specifically.

Correction to: The role of HHV-6 and HHV-7 infections in the development of fibromyalgia.

There are several typographical errors in the section "Statistical Analysis" The corrected version follows.

The role of HHV-6 and HHV-7 infections in the development of fibromyalgia.

Human herpes virus-6 (HHV-6) and human herpes virus-7 (HHV-7) are immunomodulating viruses potentially affecting the nervous system. We evaluated the influence of HHV-6 and HHV-7 infections on fibromyalgia (FM) clinical course. Forty-three FM patients and 50 control group participants were enrolled. 39.50% (n = 17) FM patients had light A delta and C nerve fiber damage, 27.91% (n = 12) had severe A delta and C nerve fiber damage. 67.44% (n = 29) FM patients had loss of warm sensation in feet, loss of heat pain sensation, and increased cold pain sensation (34.90%, n = 15 in both findings). HHV-6 and HHV-7 genomic sequences in peripheral blood DNA in 23/43 (51.00%) and 34/43 (75.50%) of samples from FM patients and in 3/50 (6.00%) and 26/50 (52.00%) of samples from the control group individuals were detected. Active HHV-6 (plasma viremia) or HHV-7 infection was revealed only in FM patients (4/23, 17.40% and 4/34, 11.80%, respectively). A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). 23/43 patients from the FM group and control group participants HHV-6 and 34/45 HHV-7 did have infection markers. A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). No difference was found between detection frequency of persistent HHV-6 and HHV-7 infection between FM patients and the control group. Statistically significant correlation was observed between quantitation of changes in QST thermal modalities and HHV-6 infection. There was no correlation between A delta and C nerve fiber damage and HHV-7 infection.

Fibrinolytic System Changes in Liver Surgery: A Pilot Observational Study.

Introduction: Bleeding occurs frequently in liver surgery. Unbalance between tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) concentrations might increase bleeding. Our aim was to analyze perioperative fibrinolytic changes during liver surgery. Materials and Methods: We evaluated 15 patients for inclusion into a prospective pilot study of liver surgery. We assessed fibrinolysis by plasma PAI-1 and t-PA: before surgery (T1), before Pringle maneuver (PM;T2), at the end of surgery (T3) and 24 h postoperatively (T4), and registered demographic and laboratory data, extent and duration of surgery, hemodynamic parameters, blood loss, and transfused volumes of blood products. Data presented as mean ± SD. Significance at P < 0.05. Results: After exclusion of six patients only undergoing biopsies, we included six women and three men aged 49.1 ± 19.6 years; two patients with liver metastases of colorectal cancer and hepatocellular carcinoma, respectively, two with focal nodular hyperplasia, two with hepatic hemangioma, and one with angiomyolipoma. Six patients underwent PM. PAI-1 plasma concentration (n = 9) rose from 6.25 ± 2.25 at T1 through 17.30 ± 14.59 ng/ml at T2 and 28.74 ± 20.4 (p = 0.007) and 22.5 ± 16.0 ng/ml (p = 0.04), respectively, at T3 and T4. Correspondingly, t-PA plasma concentration (n = 9) increased from 4.76 ± 3.08 ng/ml at T1 through 8.00 ± 5.10 ng/ml (p = 0.012) at T2 and decreased to 4.25 ± 2.29 ng/ml and 3.04 ± 3.09 at T3 and T4, respectively. Plasma t-PA level at T2 was significantly different from those at T1, T3, and T4 (p < 0.004). In PM patients, t-PA levels increased from T1, peaked at T2 (p = 0.001), and subsequently decreased at T3 and T4 (p = 0.011 and p = 0.037), respectively. Mean blood loss was 1,377.7 ± 1,062.8 ml; seven patients received blood products. Patients with higher PAI-1 levels at T3 received more fresh frozen plasma (r = 0.79; p = 0.01) and red blood cells (r = 0.88; p = 0.002). Conclusions: During liver surgery, fibrinolysis increased, as evidenced by rises in plasma PAI-1and t-PA, especially after start of surgery and following PM. Transfused volumes of blood products correlated with higher plasma concentrations of PAI-1. Confirming this tendency requires a larger cohort of patients.

Immunogenetic Markers Definition in Latvian Patients with Lyme Borreliosis and Lyme Neuroborreliosis.

The aim of this study was to determine the human leukocyte antigen (HLA)-DRB1 alleles in two groups of patients in Latvia: patients with Lyme borreliosis and patients with Lyme neuroborreliosis. The study included 216 patients with Lyme borreliosis, 29 patients with Lyme neuroborreliosis and 282 control persons. All surveyed persons were residents of Latvia. The HLA-DR genotyping was performed by polymerase chain reaction- sequence specific primer (PCR-SSP). The predisposition to the Lyme borreliosis is associated with the HLA-DRB1*07, -DRB1*17(03), -DRB1*04, -DRB1*15(02) alleles. The allele -DRB1*11(05), -DRB1*14(06) and -DRB1*13(06) were significantly more frequent in controls. In-group with Lyme neuroborreliosis differences were found for the -DRB1*07 and -DRB1*04 alleles, but only HLA-DRB1*07 allele was statistically significant after Bonferroni correction and associated with Lyme neuroborreliosis in Latvian patients.

Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients.

BACKGROUND: Many autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy) persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage - erythema migrans and 30 control (healthy) persons. HLA genotyping was performed by PCR with sequence-specific primers. RESULTS: The results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p < 0.007) and HLA-DRB1 *17 (03) (OR 8.05; p < 0.033) were increased in the Lyme disease patients. And the frequency of allele DRB1*13 (OR 0.12; p < 0.017) was lower in Borreliosis patients and higher in control group. But, significant differences in frequencies of HLA-DQ alleles we did not detect. CONCLUSIONS: HLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03) may contribute to the Lyme borreliosis development in Latvian population.

Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated. 108 ME/CFS patients and 90 practically healthy persons were enrolled in the study. Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels-by ELISA, HHV-6 variants-by restriction analysis. Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines' levels was detected in patients during active viral infection. Definite relationship was observed between active betaherpesvirus infection and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain. Neuropsychological disturbances were detected in all patients. The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection. The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines' level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS.