Human Herpesvirus Type Research Articles

Features of change of immune status indicators in individuals with active and latent forms of herpes-virus infections

Objective. The aim of the study is to investigate the peculiarities of changes in the immune status of individuals with active and latent forms of herpesvirus infections. Herpesvirus infections are an urgent problem of modern health care.
 Materials and methods. The prospective longitudinal cohort study included 92 permanent blood donors who were examined twice at 6-month intervals for the presence of specific IgM and IgG antibodies and antigens of herpes simplex viruses 1, 2, Epstein-Barr, cytomegalovirus, human herpesvirus type 6, as well as humoral immunity indicators.
 Results. In the period from October to April, 68.5 % of blood and its components donors were found to have markers of active herpesvirus infection caused by HSV 1, 2, EBV, CMV, and HHV6. The combination of the detected markers in the absence of clinical manifestations and changes in General and biochemical blood tests indicated asymptomatic reactivation of latent infection. The frequency of reactivations in the autumn and spring months is the same. The absence of IgG production after asymptomatic reactivation of HSV-2 and HHV-6 infections and an increase in IgG concentrations to HSV-1, EBV, and CMV were revealed. EBV infection is the most common among the studied nosologies (98.91 %) and is characterized by statistically significantly higher levels of specific IgG. The effect of asymptomatic reactivation of herpesvirus infections on the levels of total IDA, IgM, IgG, IDE, and CEC was not established.
 Conclusions. Asymptomatic reactivation of herpesvirus infections does not significantly affect the changes in immune status indicators, and the absence of clinical manifestations, and significant changes in General and biochemical blood tests cause epidemiological risks associated with difficulties in identifying the sources of infection.

КЛИНИЧЕСКИЕ СЛУЧАИ ВЫЯВЛЕНИЯ ХРОМОСОМНО-ИНТЕГРИРОВАННОГО ВИРУСА ГЕРПЕСА ЧЕЛОВЕКА 6-го ТИПА У ДВУХ ДЕТЕЙ

The article describes two clinical observations of the detection of chromosomally integrated human herpes virus type 6 (HHV-6). In both cases, the children were referred to an immunologist with a diagnosis of chronic infection caused by the human herpesvirus type 6, in order to exclude an immunodeficiency state and determine the strategies of treating this infection. However, during the molecular biological examination of children, a chromosomal integration of HHV-6 was determined, which led to a revision of the diagnostic search and abandoning massive antiviral therapy.

Harmful biological agents intentionally used in enterprises in Poland based on the National Register of Biological Agents

This work presents intentional use of harmful biological agents based on the National Register of Biological Agents (in Polish abbreviated as KRCB) as of July 2020. Generally, KRCB is a central database gathering notifications of intentional use of biological agents classified as risk groups 2-4 at work. Notifications were sent by 672 enterprises, including for diagnostic - 63%, research - 30% and industrial purposes - 7%. The largest number of notifications were sent by hospital-based diagnostic laboratories - 34%, laboratories other than hospital-based - 34%, and higher education and research units - 15%. In total, 7077 workers (88% women, 12% men) were exposed to biological agents intentionally used at work. The following bacteria were most frequently used: Escherichia coli (with the exception of non-pathogenic strains) - 4394 (62%) exposed workers, Staphylococcus aureus -4122 (58%), and Pseudomonas aeruginosa - 3726 (53%). Biological agents recognized by the International Agency for Research on Cancer as carcinogenic were used in 107 enterprises (16%), including the following viruses: hepatitis B virus (HBV) - 25 enterprises (4%), hepatitis C virus (HCV) - 24 (4%), human immunodeficiency virus type 1 (HIV-1) - 18 (3%), Epstein-Barr virus (EBV) - 10 (1%), human papilloma virus (HPV) - 5 (1%), human herpes virus type 8 (HHV-8) - 3 (<1%), human T-lymphotropic virus type 1 (HTLV-1) - 3 (<1%), as well as bacteria Helicobacter pylori - 18 (3%) and parasites Schistosoma haematobium - 1 (<1%). While KRCB is a unique source of information on biological agents intentionally used in workplaces, it also provides an important link in the chain of information on occupational exposure to harmful agents in Poland. Med. Pr. 2021;72(2):131-43.

Стан клітинного імунітету хворих на тонзиліт дітей, інфікованих вірусом герпеса 6 типу

Currently, the incidence of tonsillitis in children is very common and represents a serious medical and social problem. In young children, viral tonsillitis predominates, while bacterial tonsillitis is more common between the ages of 5–15. The frequency of registration of infection with viruses of the herpes group, including the human herpes virus (HHV) type 6, is increasing. The healing processes in infectious pathology are primarily due to the balanced work of the cellular and humoral links of the body’s immune response, the state of which can be influenced by concomitant infection with herpes viruses. The aim of the work was to study the cellular immune response of children with tonsillitis infected with HHV-6 type. The study of the influence of HHV-6 infection on the state of the cellular component of the immune response in 74 children with tonsillitis in the acute period and in the period of convalescence was carried out. All patients were diagnosed with a moderate form of tonsillitis; the etiological factor was hemolytic streptococcus group A. It was revealed that in children with mono-infection at the onset of the disease, there is a moderate response of cellular immunity (t = 2.76), while the presence of HHV-6 infection leads to more pronounced changes in the parameters of CD lymphocytes (t = 4.06). We found a significant increase in the content of CD16+-lymphocytes in tonsillitis of streptococcal etiology, but the maximum growth was recorded in patients with mono-infection (p &lt; 0.05). By the time of convalescence, complete recovery of T-lymphocytes in infected HHV-6 patients does not occur. The degree of deviation from the standard for the entire complex of CD-lymphocytes during the period of convalescence was more pronounced in patients with co-infection (t = 2.83). The obtained data indicate the suppression of the cellular component of the immune response in patients with tonsillitis against the background of HHV-6 infection, which requires a differentiated approach to treatment and medical supervision of such patients.

Human herpesvirus type 2 infection of primary murine astrocytes causes disruption of the mitochondrial network and remodeling of the actin cytoskeleton: an in vitro morphological study

Herpesviruses are capable of infecting not only neurons, where they establish latent infection, but also astrocytes. Since astrocytes are important for the functioning of the central nervous system (CNS), their infection may lead to serious neurological disorders. Thus, in the present study we investigated the ability of human herpesvirus type 2 (HHV-2) to infect primary murine astrocytes in vitro and the effect of infection on their mitochondrial network and actin cytoskeleton. In immunofluorescence assays, antibodies against HHV-2 antigens and glial fibrillary acidic protein (GFAP) were used to confirm that the infected cells are indeed astrocytes. Real-time PCR analysis showed a high level of HHV-2 replication in astrocytes, particularly at 168 h postinfection, confirming that a productive infection had occurred. Analysis of mitochondrial morphology showed that, starting from the first stage of infection, HHV-2 caused fragmentation of the mitochondrial network and formation of punctate and tubular structures that colocalized with virus particles. Furthermore, during the late stages of infection, the infection affected the actin cytoskeleton and induced formation of actin-based cellular projections, which were probably associated with enhanced intracellular spread of the virus. These results suggest that the observed changes in the mitochondrial network and actin cytoskeleton in productively infected astrocytes are required for effective replication and viral spread in a primary culture of astrocytes. Moreover, we speculate that, in response to injury such as HHV-2 infection, murine astrocytes cultured in vitro undergo transformation, defined in vivo as reactive astrocytosis.

Assessment of Antimicrobic, Antivirotic and Cytotoxic Potential of Alginate Beads Cross-Linked by Bivalent Ions for Vaginal Administration.

Antimicrobial agent abuse poses a serious threat for future pharmacotherapy, including vaginal administration. The solution can be found in simple polymeric systems with inherent antimicrobial properties without the need to incorporate drugs, for instance alginate beads cross-linked by bivalent ions. The main goal of the presented study was to provide improvement on the well-documented cytotoxicity of Cu2+ cross-linked alginate. Alginate beads were prepared by external ionotropic gelation by cross-linking with Cu2+, Ca2+ and Zn2+ ions, separately and in mixtures. Morphological properties, swelling capacity, ion release and efficacy against the most common vaginal pathogens (C. albicans, E. coli, E. faecalis and virus strain—human herpesvirus type 1) were evaluated. The prepared particles (particle size 1455.68 ± 18.71–1756.31 ± 16.58 µm) had very good sphericity (0.86 ± 0.04–0.97 ± 0.06). In mixture samples, Cu2+ hampered second ion loading, and was also released incompletely (18.75–44.8%) compared to the single ion Cu2+ sample (71.4%). Efficacy against the selected pathogens was confirmed in almost all samples. Although anticipating otherwise, ion mixture samples did not show betterment over a Cu2+ cross-linked sample in cytotoxicity–pathogen efficacy relation. However, the desired improvement was found in a single ion Zn2+ sample whose minimal inhibition concentrations against the pathogens (0.6–6.12 mM) were close to, or in the same mathematical order as, its toxic concentration of 50 (1.891 mM). In summary, these findings combined with alginate’s biocompatibility and biodegradability give the combination solid potential in antimicrobial use.

Human Herpes virus 7 infections in children. Clinical and laboratory aspects

Objective: to study the activity of HSV 1,2, EBV, CMV, HHV6, HHV7 in children of different age groups, to determine the frequency of various symptoms and syndromes in the examined children depending on hhv7 monoinfection and combined herpetic infection in the age aspect.Materials and methods: 56 children aged 2 to 18 years were examined at the state MEDICAL research Institute named after Prof. A. F. Agafonov in Kazan, at the BIOMED medical and diagnostic center in Kazan and at the LUCH children’s clinic in Naberezhnye Chelny (boys accounted for 62.5% of cases, girls-37.5%). Verification of the diagnosis and evaluation of the dynamics of etiological markers of the infectious process in all observed children was performed by PCR. Blood and saliva were examined to detect markers of human herpes virus type 7 (in qualitative PCR), and blood, oropharyngeal flushing, and urine were examined in semiquantitative PCR to determine other viruses from the herpes family (HHV6, CMV, EBV). In enzyme immunoassay is determined At the same time, we studied options for combining laboratory markers of herpesvirus activity and changes in the main laboratory parameters used in routine practice. We studied the dynamics of the observed parameters against the background of complex antiviral therapy for the next 3 months after the initial examination. The frequency of occurrence of various symptoms and syndromes was determined depending on the activity of various representatives of the herpes family, their combination, and the age of the subjects.Results of the study: HHV7-monoinfection is more typical for the age group of 7-14 years. The significance of mixed HHV6+HHV7 infection decreased with age. The combination of activity of 4 herpesviruses was more often registered in the age categories 2-7 years and 14-18 years. More often, patients had tonsillitis, generalized cervical lymphadenopathy, periodic temperature rise to subfebrile or febrile numbers, pharyngitis, recurrent ARI, rhinitis, which allows us to consider them as the main manifestations of HHV7 infection.Conclusion: HHV7 infection is significant in the modern pathology of the child. The presence of such syndromes as recurrent tonsillitis, cervical lymphadenopathy or isolated enlargement of submandibular lymph nodes, periodic fever, pharyngitis, recurrent ARI in combination with hepato - and/ or splenomegaly, fatigue, and headache is often associated with HHV7. HHV7-viremia is relatively rare, despite obvious clinical and laboratory signs of inflammation indicating the presence of a viral disease, which, apparently, and is the cause of underdiagnosis and lack of proper attention to this infection.

FIRST CASE REPORTED IN ECUADOR: HUMAN HERPES VIRUS TYPE 6 ENCEPHALITIS IN ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS. FIRST CASE REPORTED IN ECUADOR.

The case of a fourteen-year-old patient with Systemic Lupus Erythematosus with severe activity index and immunosuppressive treatment is described. He went to the Pediatric Emergency Department of the Carlos Andrade Marín Specialty Hospital, for presenting fever, headache, nausea, auditory hallucinations and paresis in the lower extremities. Cerebrospinal fluid was studied by Polymerase Chain Reaction, in which the presence of Human Herpes Virus type 6 or also called Roseolovirus was detected. Ganciclovir was started with a favorable clinical response in 72 hours. Conclusions: The presence of HHV-6 encephalitis should be considered in immunocompromised patients with encephalopathy and use of ganciclovir as directed therapy.

Blood virosphere in febrile Tanzanian children

ABSTRACT Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (<5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens. Trial registration: ClinicalTrials.gov identifier: NCT02225769.

Применение ультразвукового исследования в диагностике хронического лимфопролиферативного синдрома ЛОР-органов у детей младшего возраста

The aim of study was to assess the diagnostic value of ultrasound diagnostics of chronic lymphoproliferative syndrome in the young children. 88 children aged 2–3 years with pathology of the lymphadenoid ring of the pharynx, accompanied by regional cervical lymphadenitis, needing surgery were examined. Endoscopy of the nasopharynx, otomicroscopy, impedance, ultrasound examination of cervical and submandibular lymph nodes, abdominal organs, complete blood count with a manual differential, ELISA to determine specific IgM, IgG to cytomegalovirus (CMV) antigens, to human herpes virus type 6 (HCV-6) antigens, to nuclear, viral capsid and early antigens complex Epstein – Barr virus (EBV), PCR in scrapes from the oropharyngeal mucosa and blood were performed. The patients were divided into two groups: group I with pronounced lymphadenopathy (lymph nodes conglomerates 31×13 mm in size or multiple) (n = 32), group II with moderate lymphadenopathy (single symmetrical painless lymph nodes less than 16 mm in size) (n = 56). In the group I, the following were statistically significant more frequent: snore and sleep apnea (Fisher's exact test, p &lt; 0,001, odds ratio (OR) 13,00, 95% confidence interval (CI) 4,439–38,07); manifestations of asthenic vegetative and intoxication syndromes (p &lt; 0,001, OR 7,80, CI 2,248–27,06); ultrasound signs of hepatic splenic syndrome (p &lt; 0,001, OR 34,71, CI 7,185–167,7); serological markers of contamination and active stages EBV infection (p &lt; 0,001, OR 16,71, CI 4,673–55,27); markers of mixt EBV + CMV + HHV-6 infections (p &lt; 0,001, OR 16,20, CI 3,327–78,87), compared to the group II. Regional cervical lymphadenitis with lymph nodes diameter more than 16 mm on ultrasound was a sign of pronounced chronic lymphoproliferative syndrome in the young children, in which half were found to have markers of the EBV infection active stage. The development of pronounced cervical lymphadenitis is associated with hepatic splenic syndrome, usually caused by the herpesvirus infections reactivation.

Роль герпесвирусов при мужском бесплодии

Nowadays, the search for etiopathogenetic factors of infertility is an urgent medical and social task. 23 men with chronic abacterial prostatitis in a barren marriage underwent the follow-up. Herpesviruses of types IV–VI were detected in urogenital samples (urethra, ejaculate, prostate secretions) in 8 of 23 men who were treated with valacyclovir (500 mg 2 times a day for 3 months) and interferon α-2b in combination with antioxidants — vitamins E and C (rectal suppositories). Based on the personal experience of the authors, the patients were prescribed the following drug use regimen: 3 million IU twice a day — 10 days, then 3 million IU twice a day — 3 times per week for the next 3 weeks. The remaining 15 patients without any detected viruses were prescribed the following: levofloxacin 500 mg — 30 days, tamsulosin 0.4 mg — 90 days, diclofenac 50 mg — 10 days. By the end of therapy, electron microscopy and virology showed a decrease in the concentration and number of virus-positive urogenital samples, as well as a decrease in the number of spermatozoa with viral capsids. Within 6 months from the therapy initiation, the onset of pregnancy was observed in the married couples of 6 out of 8 men with herpesviruses vs. in 4 out of 11 without viruses (p=0.026). Thus, we obtained the data on the role of herpesviruses of types IV–VI in male infertility. A good reproductive effect was achieved with valacyclovir and interferon α-2b in combination with antioxidants in most patients. KEYWORDS: herpesviruses, Epstein-Barr virus, cytomegalovirus, human herpes virus type VI, male infertility. FOR CITATION: Kovalyk V.P., Gomberg M.A., Bragina E.E. et al. Herpesvirus role in male infertility. Russian Medical Inquiry. 2021;5(3):123– 129. DOI: 10.32364/2587-6821-2021-5-3-123-129.

Герпесвирусы. Часть 1

One of the urgent problems of modern medicine is the high incidence of herpesvirus infections. The high prevalence of herpesviruses in the human population of the world allow us to consider herpes a common systemic disease of the whole organism. Doctors of any specialty are faced with the clinical manifestations of herpes infection in patients, and they themselves are a risk group of chronic herpes infections formation due to constant patient contacts and frequent professional psycho-emotional overload. Herpes infections are a group of infectious diseases caused by human herpesviruses. Now it is known 8 species of herpesvirus causing various human diseases that occur in the acute (during the initial contact with the infection) or chronic form. The herpesvirus family has a number of common properties that distinguish them from other human pathogenic viruses. There are three subfamilies in the Herpesviridae family. Alpha herpesviruses (Аlphaherpesvirinae) include the two serotypes of the herpes simplex virus (HSV-1 and HSV-2), and the varicella-zoster virus (herpes zoster). Beta herpesviruses (Betaherpesvirinae) include cytomegalovirus, human herpes viruses of types 6 and 7 (HHV-5, HHV-6, HHV-7). Gamma herpes viruses (Gammaherpesvirinae) include the Epstein-Barr virus, human herpesvirus type 8 (HHV-4, HHV-8). Clinical manifestations of herpes infection depend more on the immunity state of the infected organism than on the pathogenic properties of the pathogen itself, and develop only in conditions of immunodeficiency caused by various unfavorable factors. Herpesviruses are able to damage organs, weaken the body's immunity, creating conditions for the attachment of the other infections (fungal, bacterial), which in turn can cause organ damage. The herpesvirus ability to infect all organs and tissues of the body determines a significant clinical polymorphism of diseases, as well as the necessity to study various biological liquids. Herpesviruses can be transmitted from person to person by aerosol, contact, sexual and parenteral transmission, as well as from mother to fetus or newborn, they also can act as mutagens. The pathogenesis of herpesvirus infections is rather complex and not completely understood. For a proper understanding of the disease pathogenesis it is necessary to know the main stages of reproduction of human herpesviruses. Modern laboratory techniques are used for diagnosis of herpes infection and allow obtaining more complete information for an accurate diagnosis: virological method, electron microscopy method, the method of biological sample, the polymerase chain reaction methods for the detection of viral antigens, serological, immunological, cytological and histological methods. Conclusion. The high prevalence of diseases caused by herpes viruses, the complex, not fully understood pathogenesis and high contagiousness of diseases, as well as a variety of clinical manifestations of herpesvirus infections with the possibility of the formation of mixed forms with a blurred clinical picture dictate the need for a detailed study of herpes viruses and knowledge of methods for diagnosing herpes infections

Seroepidemiology of the human herpesvirus 8 infection among people living with HIV in Taiwan, 2014-2018.

Human herpesvirus type 8 (HHV-8) can be transmitted through unprotected sex as HIV. We aimed to investigate the seroincidence of HHV-8 and associated factors among people living with HIV (PLWH). From 2014 to 2018, blood samples of PLWH on the first date of HIV care were determined for antibodies against HHV-8. Individuals testing HHV-8-seronegative at baseline were followed for at least four months to estimate the annual seroconversion rate. To identify the factors associated with HHV-8 seroconversion, we compared the clinical characteristics between seroconverters and non-seroconverters who were matched for observation duration. The HHV-8 seroprevalence increased from 8.1% in 2014 to 20.0% in 2018. HHV-8 seroconversion occurred in 154 (14.7%) PLWH after a total of 2652.16 person-years of follow-up (PYFU), resulting in an overall incidence rate of 5.62 per 100 PYFU, which increased from 3.20 to 6.84 per 100 PYFU during the study period. HHV-8 seroconverters were less likely to have chronic hepatitis B virus (HBV) infection (1.9% vs 10.6%) and more likely to be antiretroviral-naïve on entry into care (87.7% vs 75.4%) (both p<0.05). In multivariate logistic analysis, men who have sex with men (MSM) (adjusted odds ratio [aOR], 2.22; 95% CI, 1.01-4.86), being antiretroviral-naïve (aOR, 2.91; 95% CI, 1.27-6.67), and chronic HBV infection (aOR, 0.13; 95% CI, 0.03-0.61) at baseline were associated with HHV-8 seroconversion. An increasing trend of HHV-8 infection was observed among PLWH in Taiwan between 2014 and 2018. MSM and being antiretroviral-naïve were associated with higher risk for HHV-8 seroconversion.

Rheumatic diseases and viral infection: is there an association?

Viral infections, hepatitis B and C and herpesvirus-induced infections in particular, are widespread in the population. Recent years have seen the emergence of new viral infections that were previously endemic. Understanding the role of viruses in the pathogenesis of rheumatic diseases (RDs) is of great importance. First, they cause the clinical manifestations characteristic of many RDs (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, and Sjö gren's disease). The author discusses several possible mechanisms of the involvement of viruses in the development of autoimmune disorders: molecular mimicry; polyclonal B cell activation with overproduction of antibodies and immune complexes; T cell activation with cytokine overproduction. Secondly, viral infection can be reactivated during immunosuppressive therapy (also using biological agents), which is widely used to treat RDs. The review presents data on both the most common viruses (hepatitis B and C viruses, HIV, and human herpesviruses types 1–6) and more rare ones (chikungunya virus and polyomavirus) in the Russian population.

Search for viral agents in cerebrospinal fluid in patients with multiple sclerosis using real-time PCR and metagenomics.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system of unclear etiology, but there is some evidence that viral infections could be responsible for triggering autoimmune mechanisms against myelin. We searched for viral RNA and DNA in cerebrospinal fluid (CSF) of 34 MS patients and 13 controls using RT-PCR/PCR against common neurotropic viruses. In addition, shotgun DNA- and RNA-based metagenomics were done in 13 MS patients and 4 controls. Specific quantitative real-time RT-PCR/PCR testing revealed the presence of viral nucleic acid in seven (20.59%) MS patients and in one (7.69%) control patient. In MS patients the most frequently detected was human herpesvirus type 6 (HHV-6; 3 cases; 8.82%); followed by Epstein-Barr virus (EBV; 2 cases; 5.88%), varicella zoster virus (VZV; 1 case; 2.94%) and Enterovirus (EV; 1 case; 2.94%). The single identified virus among controls was EBV (7.69%). DNA and RNA metagenomic assays did not identify any known eukaryotic viruses even though three of the analyzed samples were low-level positive by specific quantitative real-time PCR. In conclusion, we detected the presence of Herpesviridae and occasionally Enteroviridae in CSF from patients with MS but their prevalence was not significantly higher than among controls. Metagenomic analysis seems to be less sensitive than real-time RT-PCR/PCR and it did not detect any potential viral pathogens.

The case of inherited chromosomal integrated human herpes virus type 6b in child with recurrent respiratory tract infections

The five years old boy with recurrent respiratory tract infections was under observation of infectiologist due to high levels of human herpes virus type 6 (HHV-6), found in patient’s blood and saliva during a few years. The patient got the medicines against the HHV-6, without any effect. We investigated the patient’s and his mom’s nails and found the HHV-6 type B, so it was inherited chromosomal integrated HHV-6. Thus, to avoid the unnecessary treatment, in case of repeated high level of HHV-6, we need to exclude chromosomal integrated HHV-6.

Marshall’s syndrome in the practice of infection disease doctor and pediatrician (сlinical case)

On the basis of literary sources, modern ideas about Marshall syndrome in children are given, as well as the main clinical and laboratory criteria for the diagnosis of this syndrome. A clinical case of Marshall syndrome in a boy 3 years 6 months infected with human herpes virus type 6 is described. Differential diagnostic criteria of Marshall syndrome and active herpesvirus infections in children are presented on the example of a clinical case.

An overview of viral infections of the nervous system in the immunosuppressed

Several viruses have the capacity to cause serious infections of the nervous system in patients who are immunosuppressed. Individuals may be immunosuppressed because of primary inherited immunodeficiency, secondary immunodeficiency due to particular diseases such as malignancy, administration of immunosuppressant drugs or organ or bone marrow transplantation. The viruses capable of such opportunistic infection of the nervous system include herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein –Barr virus (EBV), Human Herpes virus type 6 (HHV-6), JC virus (JCV), enterovirus, measles virus and Covid-19. In most cases it seems likely that immunological defence mechanisms in the immunosuppressed are deficient which creates a suitable environment for certain viruses to become opportunistic in the nervous and other systems. Further research is required both to understand these opportunistic mechanisms in more detail and also to determine how many virus infections are modified by specific inborn errors of immunological responses.

Search for Viral Infections in Cerebrospinal Fluid From Patients With Autoimmune Encephalitis.

BackgroundIt has been reported that virus-mediated brain tissue damage can lead to autoimmune encephalitis (AE) characterized by the presence of antibodies against neuronal surface antigens. In the study, we investigate the presence of viruses in cerebrospinal fluid (CSF) from patients with AE using reverse transcription polymerase chain reaction (RT-PCR)/PCR and shotgun metagenomics. MethodsCSF samples collected from 200 patients with encephalitis were tested for the presence of antibodies against antiglutamate receptor (NMDAR), contactin-associated protein 2 (CASPR2), glutamate receptors (type AMPA1/2), leucine-rich glioma-inactivated protein 1 (LGI1), dipeptidyl aminopeptidase-like protein 6 (DPPX), and GABA B receptor, and those found positive were further analyzed with real-time RT-PCR/PCR for common viral neuroinfections and shotgun DNA- and RNA-based metagenomics. ResultsAutoantibodies against neuronal cells were detected in CSF from 8 individuals (4% of all encephalitis patients): 7 (3.5%) had anti-NMDAR and 1 (0.5%) had anti-GABA B. RT-PCR/PCR identified human herpes virus type 1 (HSV-1; 300 copies/mL) and the representative of Enterovirus genus (550 copies/mL) in 1 patient each. Torque teno virus (TTV) was found in another patient using metagenomic analysis, and its presence was confirmed by specific PCR. ConclusionsWe detected the presence of HSV, TTV, and Enterovirus genus in CSF samples from 3 out of 8 AE patients. These findings support the concept of viral involvement in the pathogenesis of this disease.

Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial)

AbstractEPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384.