Case of parvovirus B19 infection and immunodeficiency in the patient with Gilbert syndrome

A case of long-term persistence of parvovirus B19 is described for the first time in a patient with Gilbert's syndrome against the background of immunodeficiency with predominance of infectious symptoms (chronic herpesvirus infection). Previously, the patient (male, 48 years old) was diagnosed with Gilbert's syndrome, chronic rhinosinusopharyngitis, and chronic herpesvirus infection. In July 2017, parvovirus B19 DNA was detected in blood. No clinical manifestations of infectious erythema were noted. The patient was admitted to the medical center of St. Petersburg Pasteur Institute. His blood samples obtained under informed consent were examined at the medical center in Central Clinical and Diagnostic Laboratory of St. Petersburg Pasteur Institute in January and June 2018 and in November 2019. ELISA test systems “Anti-Parvovirus B19 ELISA (IgM)” and “Anti-Parvovirus B19 ELISA (IgG)” (Euroimmune, Germany), as well PCR reagent kit “AmpliSens Parvovirus B19-FL” (FSB Central Research Institute of Epidemiology of Rospotrebnadzor, Russia) were used for specific diagnostics. Interferon status was determined by the induced production of IFN types I, II and circulating (serum) interferons. Moreover, we considered the laboratory data obtained earlier at different medical facilities of St. Petersburg. IgM class antibodies to the parvovirus B19 were not detected in the blood samples obtained in 2018. IgG antibody titer was 96 IU/ml and 264 IU /ml, respectively. Parvovirus B19 DNA was isolated from blood plasma, but the viral load was less than 720 IU of PVB19 DNA/ml (1.5 x 102 and 1.9 x 102 copies of DNA/ml, respectively). Clinical blood analysis, showed only minor (no more than 7%) deviations from the reference values, increased hemoglobin saturation of red blood cells (RBC), a decreased width of RBC distribution curve, and relative lymphocytosis. A deficiency of various interferon types was revealed: IFNγ level was 80 IU/ml in both samples, IFNα, IFNβ amounts varied from 80 to 160 IU/ml, respectively. The period of parvovirus B19 DNA persistence in blood was 11 months in presence of immunodeficiency. The patient was administered drugs of the interferon group. Parvovirus B19 DNA was not detected in clinical samples of November 2019; IFNα, IFNβ and IFNγ values were 160 IU/ml. We have detected recovery of lymphoid cell ratio, increase in their number, and improved indexes of interferon status.

The persistence of Epstein-Barr virus in the gastric mucosa in patients with chronic Helicobacter pylori-induced gastritis with gastric erosions and the effect on the course of the disease depending on the therapy

Ведущим этиологическим фактором хронического гастрита является инфекция Helicobacter pylori. Герпесвирусная инфекция может принимать участие в развитии и поддержании воспалительного процесса в слизистой оболочке желудка. Особое место среди герпесвирусов занимает вирус Эпштейна–Барр, которым инфицировано 95% населения. Целью работы было определить персистенцию вируса Эпштейна–Барр в слизистой оболочке желудка у больных хроническим Helicobacter pylori-индуцированным гастритом с эрозиями желудка и влияние на течение заболевания в зависимости от проводимой терапии. Под наблюдением находились 84 больных хроническим Helicobacter pylori-индуцированным гастритом с эрозиями желудка. У всех больных при первичном обращении кроме Нelicobacter pylori в слизистой оболочке желудка определялся вирус Эпштейна–Барр. Длительность заболевания составила от 1 до 10 лет. В зависимости от проводимой терапии пациенты с хроническим Helicobacter pylori-индуцированным гастритом с эрозиями желудка были разделены на 2 группы, между которыми через 1 год после первичного обращения проводилось сравнение частоты встречаемости вируса Эпштейна–Барр в слизистой оболочке желудка. Выявление Helicobacter pylori проводилось тремя методами: дыхательным уреазным тестом, цитологическим исследованием мазков и методом полимеразной цепной реакции биоптата. У пациентов с хроническим Helicobacter pylori-индуцированным гастритом с эрозиями желудка при выявлении герпесвирусной инфекции в слизистой оболочке желудка применение меглюмина акридонацетата в четырехкомпонентной эрадикационной терапии позволяет достоверно уменьшить количество вирусов Эпштейна–Барр. Сравнительная оценка полученных данных по наличию Helicobacter pylori в слизистой оболочке желудка у пациентов двух групп наблюдения свидетельствует о хорошем уровне эрадикационной терапии: в 1-й группе наблюдения эрадикация составила 91,3%, а во 2-й группе наблюдения – 89,5%. Микст-инфекция (Helicobacter pylori и вирус Эпштейна–Барр) в слизистой оболочке желудка является фактором, осложняющим процесс лечения пациентов. The leading etiological factor of chronic gastritis is Helicobacter pylori infection. Herpesvirus infection can take part in the development and maintenance of the inflammatory process in the gastric mucosa. A special place among herpesviruses is occupied by the Epstein–Barr virus, 95% of the population is infected with it. The aim was to determine the persistence of the Epstein–Barr virus in the gastric mucosa in patients with chronic Helicobacter pylori-induced gastritis with gastric erosions and to determine the effect on the course of the disease, depending on the therapy. 84 patients with chronic Helicobacter pylori-induced gastritis with gastric erosions were under observation. The Epstein–Barr virus was detected in the gastric mucosa in all patients at the initial treatment except for Helicobacter pylori. The duration of the disease was from 1 to 10 years. Depending on the treatment of chronic Helicobacter pylori-induced gastritis with gastric erosions, patients were divided into 2 groups, between them, 1 year after the initial treatment, the frequency of occurrence of Epstein–Barr virus in the gastric mucosa was compared. The detection of Helicobacter pylori was carried out by three methods: respiratoryurease test, cytological examination of smears and the method of polymerase chain reaction of the biopsy. In patients with chronic Helicobacter pylori-induced gastritis with gastric erosions, when detecting a herpesvirus infection in the gastric mucosa, the use of meglumine acridonacetate in four-component eradication therapy can significantly reduce the number of Epstein–Barr viruses. A comparative assessment of the data obtained on the presence of Helicobacter pylori in the gastric mucosa in patients of two observation groups indicates a good level of eradication therapy: in the 1st observation group, eradication was 91,3%, and in the 2nd observation group – 89,5%. Mixed infection (Helicobacter pylori and Epstein–Barr virus) in the gastric mucosa is a factor that complicates the treatment process of patients.

Natural Products and Their Derivatives against Human Herpesvirus Infection

Herpesviruses establish long-term latent infection for the life of the host and are known to cause numerous diseases. The prevalence of viral infection is significantly increased and causes a worldwide challenge in terms of health issues due to drug resistance. Prolonged treatment with conventional antiviral drugs is more likely to develop drug-resistant strains due to mutations of thymidine nucleoside kinase or DNA polymerase. Hence, the development of alternative treatments is clearly required. Natural products and their derivatives have played a significant role in treating herpesvirus infection rather than nucleoside analogs in drug-resistant strains with minimal undesirable effects and different mechanisms of action. Numerous plants, animals, fungi, and bacteria-derived compounds have been proved to be efficient and safe for treating human herpesvirus infection. This review covers the natural antiherpetic agents with the chemical structural class of alkaloids, flavonoids, terpenoids, polyphenols, anthraquinones, anthracyclines, and miscellaneous compounds, and their antiviral mechanisms have been summarized. This review would be helpful to get a better grasp of anti-herpesvirus activity of natural products and their derivatives, and to evaluate the feasibility of natural compounds as an alternative therapy against herpesvirus infections in humans.

Clinical presentation and course of multiple sclerosis in patients with herpesvirus infection

To date, the features of clinical presentation, course, and the effectiveness of therapy for multiple sclerosis (MS) in the presence of persistent herpesvirus infection (PHVI) remain poorly understood.Objective: to evaluate the features of clinical presentation and course of MS in patients with PHVI to optimize patient management.Patients and methods. We examined 122 patients with a clinically definite diagnosis of MS according to McDonald criteria (2010) (82 women and 40 men, age: 18–50 years, mean age – 37.74±11.04 years). MS duration at the time of examination was from 6 months to 20 years (mean – 8.53±7.47 years), mean Expanded Disability Status Scale (EDSS) score – 2.91±1.67. 86% of patients had relapsing-remitting MS; 14% – secondary progressive MS. 98 (80%) patients received disease modifying therapies (DMTs). All patients underwent a comprehensive clinical and neurological examination, magnetic resonance imaging (MRI). 30 healthy donors (20 women and 10 men, age: 19–62 years, mean age: 39.1±12.1 years) were included in the control group. Serum levels of type-specific IgM and IgG antibodies to herpes simplex virus (HSV) 1, 2, 6, Varicella zoster virus (VVZ), Epstein–Barr virus (EBV), cytomegalovirus (CMV) were detected, in some patients – blood and cerebrospinal fluid (CSF) polymerase chain reaction, serum and CSF oligoclonal IgG.Results and discussion. We identified two sub-groups of MS patients: with PHVI reactivation (main group, n=29) and without it (comparison group, n=93). There were a significantly higher VZV (72%) and EBV infection rate (100%) in MS patients compared to the control group (50% and 83%, respectively). Mixed herpesvirus infection prevailed over mono-infection in MS patients. In contrast to controls, the most common viral pattern in MS group was a combination of 4 herpes viruses: HSV 1, 2 + VZV + EBV + CMV (χ2=3.9; p<0.05). Patients in the main group had an unfavorable disease course: earlier MS onset, predominantly polysymptomatic onset, significantly higher relapse rate, faster disease progression, and higher EDSS and Functional Systems Scale (FSS) scores (p <0.05). MRI activity was also associated with EBV infection: new T1Gd+ and T2 foci were associated with an increase in VCA-IgM to EBV level. We also observed decreased DMTs effectiveness (χ2=4,6; p=0,033) and worse DMTs tolerability (χ2=5,3; p=0,022) in the main group.Conclusion. MS patients with PHVI reactivation, have a more unfavorable course of the demyelinating process and, therefore, a greater degree of disability, compared with age-adjusted patients without a viral infection and the same disease duration.

Cytokine tatus in patients with recurrent herpes infection

The study of the concentration of the main pro-inflammatory cytokines (IL-1β, IL-6 and TNF) in the blood serum of 48 patients with recurrent chronic herpesvirus infection was carried out. A significant increase of cytokine levels with the maximum values during the height of the disease was established. During the period of clinical symptoms’ subsidence, a decrease in their concentration with incomplete normalization is observed during the period of convalescence. Changes in the level of IL-1β, IL-6 and TNF in the blood serum of patients with recurrent herpesvirus infection depended on the period of the disease and the severity of the pathological process.

Herpesvirus Infection in a Breeding Population of Two Coexisting Strix Owls

Birds are a frequent host of a large variety of herpesviruses, and infections in them may go unnoticed or may result in fatal disease. In wild breeding populations of owls, there is very limited information about the presence, impact, and potential transmission of herpesvirus. The herpesvirus partial DNA polymerase gene was detected using polymerase chain reaction in oropharyngeal swabs of 16 out of 170 owls examined that were captured in or near nest boxes. Herpesvirus was detected in Ural owls (Strix uralensis), in both adults and young, but not in tawny owls (Strix aluco). In yellow-necked mice (Apodemus flavicollis), as the main prey of tawny owls and Ural owls in the area, herpesvirus was detected in the organs of 2 out of 40 mice captured at the same locations as the owls. Phylogenetic analysis showed that the herpesvirus sequences detected in the Ural owls differed from the herpesvirus sequences detected in the yellow-necked mice. The results indicate that herpesvirus infection exists in the breeding wild Ural owl population. However, herpesvirus-infected owls did not show any clinical or productivity deviances and, based on a phylogenetic comparison of detected herpesvirus sequences and sequences obtained from Genbank database, it seems that mice and other rodents are not the source of owl infections. The most probable transmission pathway is intraspecific, especially from adults to their chicks, but the origin of herpesvirus in owls remains to be investigated.

ASSESSMENT OF THE PREVALENCE OF HERPETIC INFECTION IN PATIENTS WITH ISCHEMIC HEART DISEASE

Сердечно-сосудистые заболевания в настоящее время являются ведущей причиной смерти в промышленно развитых странах. В настоящее время существует большой список инфекций, которые либо связаны с развитием атеросклероза, либо повышают риск развития сердечно-сосудистых заболеваний. Большое внимание в этом списке уделяется вирусам герпеса человека. Целью исследования явилось изучение распространенности герпесвирусной инфекции у больных с различной степенью тяжести коронарного атеросклероза. Материалы и методы: всем пациентам было проведено клиническое обследование, коронарография с расчетом индекса Gensini: GS0 (0 баллов) - 52 пациента, GS1 (1-15 баллов) - 54 пациента; GS2 (> 15 баллов) - 68 пациентов. Наличие вирусов герпеса (типы 1,2,4,5,6) определяли методом ПЦР с детекцией в реальном времени. Результаты исследования: в 15% случаев в группе GS0 был обнаружен ВПГ 1-го типа и в 10% случаев - вирус герпеса 2-го типа. В группе GS1 наблюдалась аналогичная тенденция: в 14% и 17% случаев были выявлены ВПГ 1-го и 2-го типов. У пациентов из группы GS2 ВПГ 6-го типа был выявлен в 35% случаев, а смешанная инфекция (ВПГ 1-го, 2-го и 6-го типов) - в 15% случаев. Вирус Эпштейна-Барра и цитомегаловирус не были идентифицированы ни у одного пациента. Корреляционный анализ установил прямую связь между наличием ВПГ 6-го типа и индексом Gensini (r=0,496, р=0,0002). Заключение: с увеличением тяжести коронарного атеросклероза отмечалось увеличение вирусной нагрузки. Среди пациентов со значительным коронарным атеросклерозом чаще встречается ВПГ 6-го типа и выявляется смешанная герпесвирусная инфекция, что требует дальнейшего изучения Cardiovascular diseases are currently the leading cause of death in industrialized countries. Currently, there is a large list of infections that are either associated with the development of atherosclerosis, or increase the risk of developing cardiovascular diseases. Much attention in this list is paid to human herpes viruses. The aim of the study was to study the prevalence of herpesvirus infection in patients with varying degrees of severity of coronary atherosclerosis. Materials and methods: all patients underwent a clinical examination, coronary angiography with the calculation of the Gensini index: GS0 (0 points) - 52 patients, GS1 (1-15 points) - 54 patients; GS2 (>15 points) - 68 patients. The presence of herpes viruses (types 1,2,4,5,6) was determined by real-time PCR detection. Results of the study: in 15% of cases in the GS0 group, HSV type 1 was detected and in 10% of cases, herpes virus type 2 was detected. In the GS1 group, a similar trend was observed: in 14% and 17% of cases, HSV types 1 and 2 were detected. In patients from the GS2 group, HSV type 6 was detected in 35% of cases, and mixed infection (HSV types 1, 2 and 6) - in 15% of cases. Epstein-Barr virus and cytomegalovirus have not been identified in any patients. The correlation analysis established a direct relationship between the presence of HSV type 6 and the Gensini index (r=0.496, p=0.0002). Conclusion: with an increase in the severity of coronary atherosclerosis, there was an increase in the viral load. Among patients with significant coronary atherosclerosis, HSV type 6 is more common and mixed herpesvirus infection is detected, which requires further study

Immunotherapy in complex treatment of acute optic neuritis associated with herpesvirus infection

Purpose. Evaluation clinical efficacy of complex treatment of optic neuritis (ON) associated with herpesvirus infection (HVI), including methods of immunotherapy. Material and methods. The clinical study involved 26 people (26 eyes) with acute ON associated with HVI. The treatment regimen for all patients within 10 days included delivery through irrigation system implanted into the retrobulbar space to optic nerve: solutions Dexamethasone on decreasing scheme, Emoxypine 1% 0.5 ml and Dicynone 12.5% 0.5 ml. All patients were divided into 2 groups depending on characteristics of therapy. The 1st group consisted of 12 patients, who were treated according to the standard method. 2nd group consisted of 14 patients who received additional intramuscular Imunofan. The duration of immunotherapy was 10–12 days. Results. Analysis of obtained datas showed that more significant positive dynamics was noted in the clinical course of ON in patients of the 2nd group of observation in comparison with the 1st group. Conclusion. The developed strategy of etiotropic and pathogenetic immunotherapy at ON associated with HVI infection, allows shortening recovery time and improving functional results of treatment in absence of relapses of disease within 1 year of follow-up. Key words: optic neuritis, herpesvirus infection, corticosteroid therapy, immunotherapy.