Browsing by Author "Rasa, Santa"

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    Association of active human herpesvirus-6, -7 and parvovirus B19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome
    (2012) Chapenko, Svetlana; Krumina, Angelika; Logina, Inara; Rasa, Santa; Chistjakovs, Maksims; Sultanova, Alina; Viksna, Ludmila; Murovska, Modra; Department of Infectology; Department of Neurology and Neurosurgery; Institute of Microbiology and Virology
    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.
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    Association of active human herpesvirus-6, -7 and parvovirus B19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome
    (2012) Chapenko, Svetlana; Krumina, Angelika; Logina, Inara; Rasa, Santa; Chistjakovs, Maksims; Sultanova, Alīna; Viksna, Ludmila; Murovska, Modra; Department of Infectology; Department of Neurology and Neurosurgery; Institute of Microbiology and Virology
    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.
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    Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
    (2018) Rasa, Santa; Nora-Krukle, Zaiga; Henning, Nina; Eliassen, Eva; Shikova, Evelina; Harrer, Thomas; Scheibenbogen, Carmen; Murovska, Modra; Prusty, Bhupesh K.; The European Network on ME/CFS (EUROMENE)
    Background and main text Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. Conclusions This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.
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    Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
    (2018-10-01) Rasa, Santa; Nora-Krukle, Zaiga; Henning, Nina; Eliassen, Eva; Shikova, Evelina; Harrer, Thomas; Scheibenbogen, Carmen; Murovska, Modra; Prusty, Bhupesh K.; Institute of Microbiology and Virology
    Background and main text: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. Conclusions: This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.
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    Human bocavirus infection markers in peripheral blood and stool samples of children with acute gastroenteritis
    (2018-11-15) Nora-Krukle, Zaiga; Vilmane, Anda; Xu, Man; Rasa, Santa; Ziemele, Inga; Silina, Elina; Söderlund-Venermo, Maria; Gardovska, Dace; Murovska, Modra; Institute of Microbiology and Virology; Department of Paediatrics
    Human bocaviruses (HBoVs) 1–4 belong to the Parvoviridae family, and they infect the respiratory or gastrointestinal tracts in children. We investigated the prevalence of HBoV1–4 DNAs in the blood and stool samples, and of HBoV1–4 IgG and IgM in the plasma samples, of children presenting with acute gastroenteritis (AGE). In addition, we identified HBoV co-infections with the five most frequent gastrointestinal pathogens. A total of 83 paired blood and stool samples were collected from children aged five years or less. Infection markers of HBoV1, 2, or 3 (viral DNA in blood and/or stool and/or antibodies) were detected in 61 out of 83 (73.5%) patients. HBoV1, 2, or 3 DNA as a monoinfection was revealed in 18.1%, 2.4%, and 1.2%, respectively, and 21.7% in totalIn 56.1% of the HBoV DNA-positive patients, the presence in stool of another virus—most frequently norovirus or rotavirus—was observed. In conclusion, this study, for the first time, illustrates the prevalence and genetic diversity of HBoVs in Latvian children with gastroenteritis, and shows a widespread distribution of these viruses in the community. HBoV1 and 2 are commonly found as single infectious agents in children with AGE, suggesting that the viruses can be as pathogenic by themselves as other enteric agents are.
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    Myalgic encephalomyelitis/chronic fatigue Syndrome (ME/CFS) : Investigating care practices pointed out to disparities in diagnosis and treatment across European Union
    (2019-12-01) European Network on ME/CFS (EUROMENE); Krumina, Angelika; Murovska, Modra; Berkis, Uldis; Nora-Krukle, Zaiga; Rasa, Santa; Rīga Stradiņš University
    ME/CFS is a chronic, complex, multisystem disease that often limits the health and functioning of the affected patients. Diagnosing patients with ME/CFS is a challenge, and many different case definitions exist and are used in clinical practice and research. Even after diagnosis, medical treatment is very challenging. Symptom relief and coping may affect how patients live with their disease and their quality of life. There is no consensus on which diagnostic criteria should be used and which treatment strategies can be recommended for patients. The purpose of the current project was to map the landscape of the Euromene countries in respect of national guidelines and recommendations for case definition, diagnosis and clinical approaches for ME/CFS patients. A 23 items questionnaire was sent out by email to the members of Euromene. The form contained questions on existing guidelines for case definitions, treatment/management of the disease, tests and questionnaires applied, and the prioritization of information for data sampling in research. We obtained information from 17 countries. Five countries reported having national guidelines for diagnosis, and five countries reported having guidelines for clinical approaches. For diagnostic purposes, the Fukuda criteria were most often recommended, and also the Canadian Consensus criteria, the International Consensus Criteria and the Oxford criteria were used. A mix of diagnostic criteria was applied within those countries having no guidelines. Many different questionnaires and tests were used for symptom registration and diagnostic investigation. For symptom relief, pain and anti-depressive medication were most often recommended. Cognitive Behavioral Therapy and Graded Exercise treatment were often recommended as disease management and rehabilitative/palliative strategies. The lack of consistency in recommendations across European countries urges the development of regulations, guidance and standards. The results of this study will contribute to the harmonization of diagnostic criteria and treatment for ME/CFS in Europe.
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    Possible chromosomal and germline integration of human herpesvirus 7
    (2017-02) Prusty, Bhupesh K.; Gulve, Nitish; Rasa, Santa; Murovska, Modra; Hernandez, Pilar Collado; Ablashi, Dharam V.; Institute of Microbiology and Virology
    Human herpesvirus 7 (HHV-7) is a betaherpesvirus, and is phylogenetically related to both HHV-6A and HHV-6B. The presence of telomeric repeat sequences at both ends of its genome should make it equally likely to integrate into the human telomere as HHV-6. However, numerous studies have failed to detect germline integration of HHV-7, suggesting an important difference between the HHV-6A/-6B and HHV-7 genomes. In search of possible germline integrated HHV-7, we developed a sensitive and quantitative real-time PCR assay and discovered that primers designed against some parts of the HHV-7 genome can frequently miss HHV-7 positive clinical samples even though they work efficiently in cell-culture-derived HHV-7 positive materials. Using a primer pair against the U90 ORF of HHV-7, we identified a possible case of germline integration of HHV-7 with one copy of viral genome per cell in both peripheral blood cells and hair follicles. Chromosomal integration of HHV-7 in these individuals was confirmed by fluorescence in situ hybridization analysis. Germline integration of HHV-7 was further confirmed by detection of ~2.6 copies of HHV-7 in the hair follicles of one of the parents. Our results shed light on the complex nature of the HHV-7 genome in human-derived materials in comparison to cell-culture-derived materials and show the need for stringent criteria in the selection of primers for epidemiological HHV-7 studies.
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    Possible Relation of Roseolovirus Infection with Fibromyalgia
    (2016-08-01) Capenko, Svetlana; Mihailova, Marija; Rasa, Santa; Krūminą, Angelika; Zazerska, Zane; Logina, Inara; Murovska, Modra; Department of Neurology and Neurosurgery; Institute of Microbiology and Virology; Department of Infectology
    Fibromyalgia (FM) is a chronic widespread pain disorder that impacts 0.5%-7% of the general population worldwide. The aetiology and pathogenesis of the disease are still unknown. Human herpesvirus-6 and-7 belong to the family Herpesviridae, subfamily Betaherpesvirinae, and genus Roseolovirus and are immunomodulating viruses potentially pathogenic to the nervous system. Presence of anti-HHV-6 and-HHV-7 antibodies and viral genomic sequences, viral loads, HHV-6 variant-specificity, and TNF-α level were studied in 41 FM patients and 50 healthy individuals using polymerase chain reactions, restriction endonuclease analysis and ELISA. There was no difference in the presence of anti-HHV-6 and anti-HHV-7 IgG class antibodies between FM patients and control group individuals. Viral sequences were found in 80.5% of FM patients and in 62.0% of controls. Significantly higher rate of concurrent HHV-6 and HHV-7 infection and higher viral loads in peripheral blood were detected in FM patients compared to the control group individuals. Plasma viremia was detected only in FM patients. Significantly higher TNF-α levels were detected in virus positive FM patients. From all positive cases only in two FM patients HHV-6A was revealed. Significantly higher detection frequency of concurrent HHV-6 and HHV-7 infection, simultaneous HHV-6 and HHV-7 activation, higher viral loads and TNF-α expression levels in primary FM patients than in control group individuals indicate the potential involvement of Roseoloviruses in development of this disorder.
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    Potential effect of two different anaesthesia techniques on the activation of hhv-6 and hhv-7 infection in relation to changes in total lymphocyte count and peripheral immune cell distribution after prolonged microvascular free flap surgery
    (2014-12-01) Vilks, Arnis; Rasa, Santa; Doniņa, Simona; Murovska, Modra; Mamaja, Biruta; Department of Doctoral Studies; Institute of Microbiology and Virology; Department of Anaesthesiology, Intensive Care and Clinical simulations
    Microvascular free flap surgery is a complex method of wound closure for large wounds. Tissue trauma, surgical stress and general anaesthesia are known immunosuppressors that may exacerbate postoperative infections. Beta-herpesviruses HHV-6 and HHV-7 are immunomodulating viruses highly prevalent in the population of healthy individuals, which can interfere with the function of the host immune system. These viruses can be reactivated in immunosuppressed conditions. The aim of this study was to monitor the potential effects of two different anaesthesia techniques - general anaesthesia (GA) and regional anaesthesia (RA) - on the activation of HHV-6 and HHV-7 infection in relation to changes in the total lymphocyte count and peripheral immune cell distribution after microvascular free flap surgery. We found significant increase in the frequency of active HHV-7 infection after surgery (p < 0.05) in the GA group. In the RA group changes were not significant. The activation of HHV-7 infection was associated with decrease in the total lymphocyte count post-operatively in patients from the GA group. The data of our study show that reconstructive flap surgery under GA is linked with more frequent postoperative lymphopenia, which is a potential post-operative immunosuppressor that probably triggers the activation of HHV-6 and HHV-7 infection.
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    Presence of human bocavirus 1 and other respiratory viruses in children with lower respiratory tract infection in Latvia
    (2019-05-01) Vilmane, Anda; Ziemele, Inga; Rasa, Santa; Terentjeva, Anna; Murovska, Modra; Gardovska, Dace; Lin, Yung Cheng; Nora-Krukle, Zaiga; Institute of Microbiology and Virology; Department of Paediatrics; Faculty of Medicine
    Lower respiratory tract infection (LRTI) is the major cause of morbidity and mortality of children in the world. In addition to respiratory syncytial virus, influenza virus types A and B, parainfluenza types 1, 2 and 3, and adenoviruses, several new respiratory viruses associated with LRTI were discovered in the 21 st century. These are metapneumovirus, coronaviruses NL63 and HKU1, parainfluenza virus type four and human bocavirus one (HBoV1). HBoV1 was discovered in 2005 and is considered as the fourth most prevalent respiratory virus worldwide. However, the high frequency of co-infections detected together with HBoV1 raises doubt about whether HBoV1 is a true pathogen or just a bystander. This is the first study aimed to determine the presence of HBoV1 and 18 other respiratory viruses in nasopharyngeal aspirates (NPA) of children with LRTI in Latvia. Using multiplex real-time polymerase chain reaction method, the HBoV1 genomic sequence was detected in 60.0% of NPA samples, showing that HBoV1 prevalence is high among children with LRTI in Latvia. HBoV1 mono-infection was revealed in 6.67%. The most common co-infections associated with HBoV1 were rhinovirus, adenovirus, respiratory syncytial virus A and B, metapneumovirus, and enterovirus.
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    Presence of Human Bocavirus 1 in Hospitalised Children with Acute Respiratory Tract Infections in Latvia and Lithuania
    (2016-08-01) Nora-Krūkle, Zaiga; Rasa, Santa; Vilmane, Anda; Grāvelsiņa, Sabīne; Kālis, Mārtiņš; Ziemele, Inga; Naciute, Milda; Petraitiene, Sigita; Mieliauskaite, Diana; Klimantaviciene, Migle; Girkontaite, Irute; Liu, Hsin Fu; Lin, Jih Hui; Lin, Yung Cheng; Chan, Hsiu Chuan; Gardovska, Dace; Murovska, Modra; Institute of Microbiology and Virology; Rīga Stradiņš University
    Human bocavirus 1 (HBoV1) is a parvovirus recently found to be a possible aetiologic agent of acute respiratory disease in children. We conducted the first clinical and molecular study on this virus in Latvia (LV) and Lithuania (LT). The aim of the study was to determine the occurrence of HBoV1 in respiratory tract samples taken from hospitalised children with acute respiratory tract infections in LV and LT. In total 186 children with age one to 50 months, and who fulfilled criteria of acute respiratory tract infection, including lower respiratory tract infections, with or without fever, were included in this study. A nasopharyngeal aspirate was obtained from each patient on admission. DNA was isolated and polimerase chain reaction (PCR) performed targeting the HBoV1 NS1sequence. HBoV1 positive samples were sequenced and phylogenetic analysis was performed. HBoV1 sequence was detected in 42 (32%) of 130 LV and in 8 (14%) of 56 LT samples. In LV the majority of patients with HBoV1 infection were observed in February while in LT in October. The phylogenetic tree for HBoV1 indicated that isolates of HBoV1 cluster closely and include almost all of the isolates in this study. HBoV1 is common in Latvia and Lithuania and might be a significant pathogen that contributes to acute respiratory tract infections in children.
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    The role of HHV-6 and HHV-7 infections in the development of fibromyalgia
    (2019) Krumina, Angelika; Chapenko, Svetlana; Kenina, Viktorija; Mihailova, Marija; Logina, Inara; Rasa, Santa; Gintere, Sandra; Viksna, Ludmila; Svirskis, Simons; Murovska, Modra
    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.
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    The role of HHV-6 and HHV-7 infections in the development of fibromyalgia
    (2019-04-15) Krumina, Angelika; Chapenko, Svetlana; Kenina, Viktorija; Mihailova, Marija; Logina, Inara; Rasa, Santa; Gintere, Sandra; Viksna, Ludmila; Svirskis, Simons; Murovska, Modra; Department of Infectology; Department of Neurology and Neurosurgery; Rīga Stradiņš University; Department of Family Medicine; Institute of Microbiology and Virology
    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.
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    Thermal Quantitative Sensory Testing in Fibromyalgia Patients
    (2015-09-01) Mihailova, Marija; Logina, Ināra; Rasa, Santa; Čapenko, Svetlana; Murovska, Modra; Krūmiņa, Angelika; Department of Neurology and Neurosurgery; Institute of Microbiology and Virology; Department of Infectology
    Fibromyalgia (FM) is a chronic disorder manifested by diffuse musculoskeletal pain, fatigue, sleep, and emotional disturbance. The disorder is probably associated with dysfunction of C and A delta peripheral nerve fibres. Thermal quantitative sensory testing (QST) was used to analyse thinly myelinated A delta fibres and nonmylinated C fibres, which function in the nociceptive sensory system, and the spinothalamic pathway. The observation that FM pain has neuropathic nature increased the value of QST as an additional diagnostic tool. The research group included 51 patients. Somatic symptoms were assessed using the Fatigue Severity Score (FSS), Fibromyalgia Impact Questionnaire (FIQ) and American College of Rheumatology (ACR) 2010 year diagnostic criteria. QST was performed by using thermal stimulus at wrist and feet. QST results were compared with 20 non-FM controls matched for age and sex. FM patients showed significant alteration of thermal perception and pain threshold compared with that in healthy controls, which demonstrated possible neuropathic pain nature in FM patients. Changes were more expressed in warm perception and heat pain threshold, which probably indicates that in FM patients C fibres are more damaged and warm perception and warm pain threshold are more sensitive, which may be used as FM diagnostics. We also found statistically significant negative correlations between warm and cold perception thresholds and between heat and cold pain thresholds, reflecting central sensitization or a defective pain inhibitory system.