Human Herpesvirus Type Research Articles

Clinicopathological characteristics of 3 probable pediatric cases with acute severe hepatitis of unknown aetiology

BackgroundAcute severe hepatitis with unknown aetiology in children (ASHep-UA) has become a global health alert. This article reported clinicopathological characteristics of 3 probable ASHep-UA cases. MethodsWe respectively collected serological data and liver biopsies of 3 suspected cases of ASHep-UA. Neutralizing antibodies titer for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants were determined by virus neutralization test (VNT). Histological assessment, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human adenoviruses (HAdV), adeno-associated virus (AAV2), human herpes virus type 6 (HHV-6) were performed to identify possible aetiologies. ResultsRemarkable elevation of transaminase (median ALT level, 1100 IU/liter; median AST level, 500 IU/liter) were revealed with undetectable hepatitis A-E and non-hepatotropic virus in both sera and tissues. Weakness, jaundice, pale stools and splenomegaly were observed. Interestingly, two individuals had SARS-CoV-2 Omicron variants infection. Histologically, moderate or severe lobular necroinflammation, active interface hepatitis and portal inflammatory infiltrate with lymphocytic, plasma cells, neutrophils and eosinophilic cells were noted. ConclusionsThe exact aetiology of ASHep-UA was still unknown. By reporting the 3 probable cases, we expect to enrich the clinical experience in diagnosis and treatment of ASHep-UA as well as the pathological characteristics.

Idiopathic multicentric Castleman's disease with TAFRO syndrome: a case report

Abstract Introduction/Objective Multicentric Castleman's disease(MCD) is a nonneoplastic lymphoproliferative disorder. Individuals affected by MCD exhibit systemic symptoms accompanied by the presence of multiple enlarged lymph nodes. MCD can be associated with human herpesvirus type-8, POEMS syndrome, or idiopathic (iMCD). TAFRO syndrome, a clinical subtype of MCD is a recently recognized disorder with an unclear cause, it comes with a combination of symptoms, namely thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly. This case report aims to shed light on the diagnostic challenges due to the rarity and nonspecific nature of TAFRO syndrome. Methods/Case Report We report a 30-year-old female who presented with night sweats, fever, fatigue, and cough. She had significant leucocytosis, lymphopenia, thrombocytopenia, anemia requiring transfusion, and elevated creatinine, CT showed ground glass opacities in the lungs and extensive lymphadenopathy. Axillary lymph node excisional biopsy revealed paracortical hyperplasia with increased vascularity, extensive polytypic plasmacytosis, and some follicular hyperplasia. On IHC staining it was positive for CD20, CD79a, PAX 5, and negative cyclin D1 for B lymphocytes. T lymphocytes were positive for CD3, CD5, CD2, CD7, CD4>CD8, Bcl2 and CD43. Plasma cells were composed mainly of IgG cells and some IgG4(IgG4/IgG <20%). HHV8 was negative. Flow cytometry showed 89% lymphocytes with a heterogenous population of T-cells and polytypic B cells. Serology revealed markedly elevated IL- 6, IL-2, VEGF CRP, and ESR while HIV and ANA were negative. Bone marrow biopsy was suggested. A final diagnosis of idiopathic multicentric castle man disease suggestive of TAFRO syndrome was made. The patient received steroids and is currently on siltuximab. Results (if a Case Study enter NA) NA Conclusion Our case fulfills at least four of the five major diagnostic criteria of TAFRO syndrome. It serves as a valuable addition to the scarce literature on TAFRO syndrome, providing insights into its diagnostic challenges

Clinical and Laboratory Diagnosis of Exanthems Among Japanese Children Younger Than 6 Years Old in the Post-Measles-Rubella Vaccine Era.

Exanthems are a common reason for visits to the pediatric emergency department. However, epidemiological data in the post-measles-rubella vaccine era is limited. We sought to determine the recent causes of exanthems in children younger than 6 years old in the pediatric emergency department. A prospective single-center study was conducted in Japan from August 2019 to March 2020. Children younger than 6 years old with exanthems were enrolled. Exanthems were classified into 7 morphological patterns. Varicella, herpes zoster, impetigo, urticaria and Kawasaki disease were diagnosed clinically. Nasopharyngeal swab specimens were collected from patients with nonspecific exanthems and evaluated by polymerase chain reaction (PCR) assays capable of detecting 24 pathogens. The final diagnosis was made by discussion of 3 physicians based on clinical course and microbiology. There were 9705 pediatric visits, of which 296 (3%) had exanthems and were younger than 6 years old. Clinical diagnosis was possible for 160 (54%), including urticaria in 110 (37%), Kawasaki disease in 29 (10%), impetigo in 10 (3%), varicella or herpes zoster in 7 (2%) and group A Streptococcus in 4 (1%). Among the remaining 136 (46%) children, 75 (25%) underwent testing by PCR. One or more pathogens were detected in 49 (65%), specifically enterovirus in 14 (19%), cytomegalovirus in 13 (17%), human herpesvirus type-6 in 12 (16%), adenovirus in 11 (15%) and human herpesvirus type-7 in 8 (11%). Final infectious disease diagnoses were roseola infantum in 11 (15%), enterovirus in 9 (12%), adenovirus in 6 (8%), mixed virus infection in 5 (7%), group A Streptococcus in 3 (4%), parechovirus-A in 3 (4%) and influenza in 3 (4%). The most common causes of pediatric exanthems were noninfectious diseases and viral exanthema. PCR assay was instrumental for etiological diagnosis of nonspecific exanthems.

Synthesis, biological activity, and molecular dynamic studies of new triazolopyrimidine derivatives

New series of triazolopyrimidine derivatives were designed, synthesized and fully characterized by spectroscopic tools. The new compounds were investigated as antimicrobial agents against two bacterial and two fungal strains. The antimicrobial results revealed that the triazolopyrimidine derivative 3b exhibited excellent antibacterial and antifungal activity higher than the standard drug (Neomycin). Additionally, we studied the antiviral activity of the three compounds against two different viruses (Corona Virus 229E, and herpes). The fluoro triazolopyrimidine derivatives 3a,b showed significant antiviral activity against low pathogenic Corona virus (229E) with selective index of 25.87 and 18.15 respectively. The same compounds showed good antiviral activity against human herpes type 2 with selective index of 17.7 and 11. The molecular dynamics simulation (MD) studies were also implemented to assign the interaction as well as the stability of the protein–ligand complex in motion.

The Molecular Prevalence of Varicella-Zoster Virus and Human Herpesvirus Types 6 and 7 in Sperm Samples of Infertile Men

Background and Aims: Human herpes virus types 6 and 7 (HHV-6, HHV-7) can remain latent in the urogenital tract epithelial cells. Varicella-Zoster virus (VZV) is among the Alphaherpesviruses infecting most people during childhood. This virus can remain latent in the ganglionic neurons. The latent infection can reactivate through weakness, suppression of the immune system, and aging. Therefore, this study investigated the molecular prevalence of HHV-6, HHV-7, and Varicella-Zoster virus in sperm samples from infertile men.
 Materials and Methods: Sperm samples from 82 infertile patients were collected from infertility centers in Tehran. Chromatin health levels and sperm DNA examinations were carried out using sperm DNA fragmentation index kits. Viral nucleic acids were extracted from the samples. The presence of VZV, HHV-6, and HHV-7 genomes was examined through the conventional polymerase chain reaction assay.
 Results: The average age was 37.3 ± 6.1 years. The mean sperm motility percentage was 33.6 ± 2%. Infertile men's mean DNA fragmentation index was 27.2 ± 1.2. This study shows a 7.3% and 4.9% prevalence for HHV-6 and VZV, respectively, and the absence of HHV-7 in sperm specimens.
 Conclusion: Although the infection rates of these herpesviruses seem relatively low, more comprehensive and multi-center studies are required to obtain more accurate results.

311.3: Introduction of deceased organ donor screening for Human Herpes Virus type 8 in the UK.

311.3: Introduction of deceased organ donor screening for Human Herpes Virus type 8 in the UK.

Enteroviral central nervous system infections in patients with Lyme neuroborreliosis

Patients with Lyme neuroborreliosis (LNB) are rarely tested for the presence of neurovirulent viruses other than tick-borne encephalitis virus (TBEV); however, such coinfections could be of clinical importance. The aim of the study was to search for the presence of neurotropic viruses in a LNB patients.Fourteen patients admitted with signs and symptoms of neuroinfection who were eventually diagnosed to have LNB (according to the guidelines of the European Federation of Neurological Societies) were subjects of the study. Sera and cerebrospinal fluid (CSF) collected at the time of initial presentation were tested for viral pathogens most common in our geographical area: human enteroviruses (EV), herpes simplex virus type 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus type 6, human adenoviruses, and TBEV using PCR/RT-PCR and serological assays. RNA and DNA-based metagenomic next-generation sequencing (mNGS) was used to detect other viral pathogens.EV was detected in CSF from two (14 %) LNB patients and viral loads were similar (220 and 270 copies/ml). The mMGS analysis were performed on CSFs from 10 patients and generated a total 213,750,885 NGS reads, 0.05 % of which were viral. However, none of potential pathogens fulfilled the criteria for positive viral detection by mNGS.Using a number of PCR/RT-PCR assays and mNGS we identified EV infection in two out of 14 LNB patients. The possible co-occurrence of enterovirus and Lyme neuroborreliosis infections may warrant further research.

The Association of HHV-6 and the TNF-α (-308G/A) Promotor with Major Depressive Disorder Patients and Healthy Controls in Thailand.

Major depressive disorder (MDD) is a silent global health problem that can lead to suicide. MDD development is suggested to result from numerous risk factors, including genetic factors. A precise tool for MDD diagnosis is currently not available. Recently, inflammatory processes have been identified as being strongly involved in MDD development and the reactivation of human herpesvirus type 6 (HHV-6), upregulating cytokines such as TNF-α, which are associated with MDD. Therefore, this study aimed to determine the association of HHV-6 with genetic factors, especially TNF-α mutation, in MDD patients and their relatives compared to healthy controls. The Patient Health Questionnaire (PHQ-9) was used to evaluate MDD status, and 471 oral buccal samples were investigated for HHV-6 infection and viral copy number by qPCR. TNF-α (-308G/A) gene mutation and the cytokines TNF-α, IL-6, and IL-10 were analyzed by high-resolution melting (HRM) analysis and enzyme-linked immunosorbent assay (ELISA). Whole-exome sequencing of buccal samples was performed to analyze for genetic factors. The results showed significantly higher HHV-6 positivities and viral loads in MDD patients (15/59 (25.67%) and 14,473 ± 16,948 copies/µL DNA) and their relatives (blood relatives 17/36 (47.22%) and 8146 ± 5656 copies/µL DNA); non-blood relatives 7/16 (43.75%) and 20,721 ± 12,458 copies/µL DNA) compared to the healthy population (51/360 (14.17%) and 6303 ± 5791 copies/µL DNA). The TNF-α (-308G/A) mutation showed no significant difference. Surprisingly, 12/26 (46.15%) participants with the TNF-α (-308G/A) mutation showed HHV-6 positivities at higher rates than those with wild-type TNF-α (-308G) (70/267 (26.22%)). HHV-6-positive participants with TNF-α (-308G/A) showed higher levels of TNF-α, IL-6, and IL-10 than those of negative control. Exome analysis revealed that common mutations in immune genes were associated with depression. Therefore, this study unveiled the novel association of inflammatory gene TNF-α (-308G/A) mutations with HHV-6 reactivation, which could represent a combined risk factor for MDD. This result could induce further research on MDD development and clinical applications.

Pathogen Profiles in Outpatients with Non-COVID-19 during the 7th Prevalent Period of COVID-19 in Gunma, Japan.

The identification of pathogens associated with respiratory symptoms other than the novel coronavirus disease 2019 (COVID-19) can be challenging. However, the diagnosis of pathogens is crucial for assessing the clinical outcome of patients. We comprehensively profiled pathogens causing non-COVID-19 respiratory symptoms during the 7th prevalent period in Gunma, Japan, using deep sequencing combined with a next-generation sequencer (NGS) and advanced bioinformatics technologies. The study included nasopharyngeal swabs from 40 patients who tested negative for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) using immuno-chromatography and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR) methods. Comprehensive pathogen sequencing was conducted through deep sequencing using NGS. Additionally, short reads obtained from NGS were analyzed for comprehensive pathogen estimation using MePIC (Metagenomic Pathogen Identification Pipeline for Clinical Specimens) and/or VirusTap. The results revealed the presence of various pathogens, including respiratory viruses and bacteria, in the present subjects. Notably, human adenovirus (HAdV) was the most frequently detected virus in 16 of the 40 cases (40.0%), followed by coryneforms, which were the most frequently detected bacteria in 21 of the 40 cases (52.5%). Seasonal human coronaviruses (NL63 type, 229E type, HKU1 type, and OC43 type), human bocaviruses, and human herpesviruses (human herpesvirus types 1-7) were not detected. Moreover, multiple pathogens were detected in 50% of the subjects. These results suggest that various respiratory pathogens may be associated with non-COVID-19 patients during the 7th prevalent period in Gunma Prefecture, Japan. Consequently, for an accurate diagnosis of pathogens causing respiratory infections, detailed pathogen analyses may be necessary. Furthermore, it is possible that various pathogens, excluding SARS-CoV-2, may be linked to fever and/or respiratory infections even during the COVID-19 pandemic.

Detection of human herpesvirus 6 in pediatric CSF samples: causing disease or incidental distraction?

Interpretation of human herpesvirus type 6 (HHV6) detection in the cerebrospinal fluid (CSF) of children can be complex; the virus can cause acute infection, reactivation, or can be inherited chromosomally integrated (iciHHV6). Our objectives were to determine the prevalence of HHV6 including iciHHV6 in CSF and compare the clinical and laboratory characteristics with and without iciHHV6 in our patient population. Overall, the prevalence of HHV6 and iciHHV6 was 2.4% and 0.85%, respectively. Children with iciHHV6 were significantly younger and less likely to present with fever. Septic infants (≤60 days) accounted for 65.2% (15/23) of the iciHHV6 patients. Patients with iciHHV6 had higher viral loads in CSF and whole blood. Twenty-one (91.3%) patients with iciHHV6 and 12 (33.3%) without ici-HHV6 were determined to have an incidental detection of HHV6 not associated with presenting symptoms. Molecular detection of HHV6 in CSF is not always associated with HHV6 infection and may represent iciHHV6 particularly in infants evaluated for sepsis.

Scrotal Kaposi's Sarcoma in HIV-negative Patient: A Case Report and Review of the Literature.

Background: Kaposi's sarcoma (KS) is an indolent angio-proliferative tumor proliferation with spindle cells originating from endothelial and immune cells infected with human herpes virus type 8. (HHV-8: also known as Kaposi sarcoma herpes virus [KSHV]). HHV-8 was identified as the causative agent of KS. This virus is present in 95-98% of cases with KS. Kaposi's sarcoma was first described by a Hungarian dermatologist 1872 named Moritz Kaposi.[1]
 The lesions are characterized by the proliferation of spindle cells of endothelial origin, which present different degrees of abnormal vascularization, inflammatory infiltrates, and fibrosis. Kaposi's Sarcoma (KS) is a malignancy that generally affects the skin, and can be systemic with internal organ involvement. It originates from the vascular endothelium. KS's relationship with human immunodeficiency virus (HIV) infection is well known.
 In this article, we will present a 73-year-old male patient with 3 purple scrotal lesions up to 0.5 cm in size.
 Conclusion; Kaposi's sarcoma of the scrotum in a negative patient is a rare pathology. However, in cases of scrotal lesions that last over time, a differential diagnosis should be made and Kaposi's sarcoma should be taken into consideration. Also, a screening for other accompanying lesions, especially a detailed examination of the gastrointestinal tract is important in cases of Kaposi’s sarcoma of the scrotum.

Viral Encephalitis (Human Herpes Virus Type 6) after COVID-19 in a Child: Clinical Case

Background. Immune system disorders early after COVID-19 are associated with high risk of other infections development, including viral ones. Their diagnosis is complicated especially in the absence of clinical symptoms of primary infection and alongside with serious disease course. There are no reports on encephalitis development due to reactivation of latent viral infection.Clinical case description. Girl, 4 years-old, had psycho-neurological symptoms followed by tonic seizures on the next day. The child was hospitalized on the 3rd day after disease onset with preliminary diagnosis of viral encephalitis. The child has contacted with patients with laboratory-confirmed new coronavirus infection 3-4 weeks before the disease onset, later she had signs of mild respiratory infection (no examination of SARS-CoV-2 was carried out). Autoimmune nature of central nervous system injury was suspected after excluding a wide range of infections (negative PCR results for SARS-CoV-2, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, toxoplasma, enterovirus), however it was not confirmed later on. Human herpes virus type 6 was revealed via blood tests and oropharyngeal swаb on the 15th day of disease. High concentration of IgG antibodies to SARS-CoV-2 was found was revealed as well. Treatment (antibacterial, anticonvulsant, anticoagulant, antiviral, immunosupportive, and sedative therapy, glucocorticosteroids) did not achieve significant improvement. Brain MRI (on the 23rd day of the disease) has shown leukoencephalopathy zones in subcortical white matter of convexital surfaces of parietal and occipital lobes, subatrophic changes in white matter of cerebral hemispheres with moderate vicarious enlargement of the subarachnoid spaces. Disease progression led to patient’s death on the 32nd day after first signs appearance.Conclusion. The development of severe viral encephalitis (as a result of primary herpes virus infection or its reactivation) in the early period after mild COVID-19 is shown. Its cause-effect relations require further examination.

Seroprevalence of human herpesvirus type 8 (HHV-8) in blood donors at Laquintinie Hospital of Douala (LHD), Cameroon

Background: The Human Herpesvirus type 8 (HHV-8), also called Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus. Its prevalence is high in many sub-Saharan African countries and some Asian areas. HHV-8 is transmitted through saliva and is acquired in early childhood. HHV-8 can also be transmitted sexually and by organ transplant or blood transfusion. Cameroon is an endemic area. That is why, for improving transfusion safety purpose, we assessed the HHV-8 infection rate in blood donors since the risk of transmission by blood transfusion was shown. Material and methods: Blood samples were collected from blood donors at Laquintinie Hospital of Douala (Cameroon) blood bank for 5 months. Participants were from different ages. Collected samples were tested for detection of antibodies against HHV-8 using enzyme-linked immunosorbent assay (ELISA). Data analysis was perform and P-value of 0.05 was statistical significance threshold. Results: Our result showed 2.2 % (2/91) seroprevalence rate of HHV-8 in blood donors. The two positive results were single and male-gendered. These observations were not statistically significant (P=0.6959 and P=0.851 respectively). Males were the most represented of our participants (92.31%). The mean age of our subject was 29±7 years. None of the studied population were at risk of HHV-8 infection. However, young adults aged between 18 to 28 years (54.94%) were the most represented. No evident association with socio-demographic data such as age, sex, level of education, and marital status was observed. Though, the high the educational level was the fewer we had volunteers for blood donation. Also, the number of blood donors decreased in an age-depending manner. Conclusion: Thus in our study, the HHV-8 infection rate was low in blood donors. Even though the potential risk of transmission might be low, we should consider HHV-8 infection check in some special cases such as immunodeficiency.

Comprehensive Metabolite Profiling of Chemlali Olive Tree Root Extracts Using LC-ESI-QTOF-MS/MS, Their Cytotoxicity, and Antiviral Assessment.

The large quantity of olive roots resulting from a large number of old and unfruitful trees encouraged us to look for ways of adding value to these roots. For this reason, the current research work is devoted to the valorization of olive roots by identifying active phytochemicals and assessing their biological activities, including the cytotoxicity and antiviral potential of different extracts from the Olea europaea Chemlali cultivar. The extract, obtained by ultrasonic extraction, was analyzed using the liquid chromatography-mass spectrometry technique (LC-MS). The cytotoxicity was evaluated through the use of the microculture tetrazolium assay (MTT) against VERO cells. Subsequently, the antiviral activity was determined for HHV-1 (Human Herpesvirus type 1) and CVB3 (Coxsackievirus B3) replication in the infected VERO cells. LC-MS analysis allowed the identification of 40 compounds, classified as secoiridoids (53%), organic acids (13%), iridoids (10%), lignans (8%), caffeoylphenylethanoid (5%), phenylethanoids (5%),sugars and derivatives (2%), phenolic acids (2%), and flavonoids (2%). It was found that extracts were not toxic to the VERO cells. Moreover, the extracts did not influence the appearance of HHV-1 or CVB3 cytopathic effects in the infected VERO cells and failed to decrease the viral infectious titer.

Association between atopic dermatitis, autoimmune illnesses, Epstein-Barr virus, and cytomegalovirus.

Atopic dermatitis (AD) is a Th2-driven inflammatory skin disease that has been associated with other autoimmune illnesses (AI) and has a well-known predisposition to infection with herpes simplex virus infection. Yet, few studies have evaluated the association between atopic dermatitis, autoimmune illness, and other human herpes virus (HHV) infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). We aimed to evaluate the association between AD, specific AIs, CMV, and EBV in a random sample of the Optum Clinformatics Data Mart database, a US administrative claims database. AD was defined based on ICD diagnostic codes. Patients with AD were exact matched to those without AD on sex, age at enrollment, time observed in the dataset and census division. Our outcomes of interest were rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), CMV, and EBV infection as defined by specific ICD codes. Logistic regression models were used to examine the association between AD and our outcomes of interest [odds ratio (95% confidence intervals)]. Our full cohort included 40,141,017 patients. In total, 601,783 patients with AD were included. As expected, patients with AD had a higher prevalence of asthma and seasonal allergies versus controls. Individuals with AD have an increased risk of EBV, CMV, RA, CD, UC, and MS. While we cannot demonstrate a causal association, the observed associations between AD and AI may be in part mediated by these types of HHV (i.e., CMV and EBV), a finding that merits further study.

Contactin-associated protein-2 and anti-aquaporin-4 antibody positive autoimmune encephalitis secondary to herpes simplex encephalitis: A case report.

Recurrent herpes simplex encephalitis (HSE) can easily induce autoimmune encephalitis (AE). However, there are few reports of anti-contactin-associated protein-2 (CASPR2)-related encephalitis, especially with positive anti-aquaporin 4 (AQP4) antibodies. A 14-year-old boy was admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University for "headache, dizziness, and fever for four days" with positive anti-CASPR2 and anti-AQP4 antibodies in the cerebrospinal fluid. Cranial MRI showed lesions in the right hippocampus, amygdala, and insular lobe, with local sulcus enhancement in the right insular, temporal, and frontal lobes. The fluid-attenuated inversion recovery was significantly enhanced. Human herpes virus type I was detected by cerebrospinal fluid metagenomic testing. The patient was diagnosed with AE secondary to HSE, with positive anti-CASPR2 and anti-AQP4 antibodies. After 2 weeks of immunoglobulin and methylprednisolone immunomodulatory therapy, acyclovir antivirus, mannitol dehydration, reducing intracranial pressure, and other symptomatic support therapy. The patient's symptoms significantly improved, with no complaints of discomfort, and he was discharged for observation. The patient was followed up a month after discharge and had no complaints of discomfort. CASPR2 and anti-aquaporin-4 antibody-positive AE have not been reported to be positive. This case will raise awareness of CASPR2 and anti-aquaporin-4 antibody-positive AE secondary to HSE, strengthen diagnostic capacities, and provide advice to treat it.

Menejit Ön tanısıyla Başvuran Hastalarda Beyin Omirilik Sıvı Sonuçlarının Değerlendirilmesi

Aim: It was aimed to determine the microorganisms and antibiotic susceptibilities obtained from cerebrospinal fluid samples (CSF).
 Material and Methods: CSF samples of 138 patients who admitted with a prediagnosis of meningitis to Ondokuz Mayıs University Pediatric Emergency Department between 01/01/2021-01/01/2022 was included. CSF cultures, identification of bacteria and their antibiotic susceptibilities were evaluated by VITEK 2 (bioMeriux, France) automated identification system. If the growth was detected by blood culture system, the specimen was cultivated onto the 5% blood agar, Eosin Methylene Blue agar and chocolate agar. Also, CSF samples were studied for both viral and bacterial agents with the Smart Cycler (Cepheid, USA) device working with Real-Time PCR method. In this system, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Cytomegalovirus, Herpes simplex type-1, Herpes simplex type-2, Human herpes virus type-6 (HHV-6), Varicella zoster virus and Epstein Barr virus agents were detected. 
 Results: Of the 138 CSF samples, 50,88% were male and 49,12% were female. The mean age of the patients was 36 ± 55 months. Bacterial agents were detected in 18 (13,8%) of the CSF samples and viral agents in 12 (9,2%) samples. Staphylococcus epidermidis (64.6%), Staphylococcus aureus (7.7%) and Streptococcus pneumonia (6.9%) took the first three places in bacterial agents. Among the viral agents, HHV-6 was the most common followed by Enteroviruses.
 Conclusion: It has been observed that the profiles and resistance status of microorganisms frequently seen in CSF have changed over the years.

The incidence of infection in tumor and eye fluid system, and specific humoral immunity to herpes viruses in patients with uveal melanoma

Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far. Research goal to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma. 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), EpsteinBarr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs. EBV DNA was present in tumor tissue in 20.6% of cases, in vitreous body in 4.2%, in blood plasma in 2.7%, and was not found in aqueous humor. Ig G antibodies to HSV-1, 2 and CMV were detected in 97.3% of cases, VZV 94.6%, HHV-6 32.4%, antibodies to HHV-8 were not detected. 20 patients (55.6%) had reactivation of chronic HSV-1, 2 infection, and 14 (38.9%) patients had reactivation of CMV infection. Markers of chronic EBV infection were found in all patients, its atypical reactivation was observed in 2 cases (5.4%). Our findings suggest the possible participation of EBV in the oncogenesis of the uveal tract and emphasize the need for further in-depth study of this problem.

Malignancy and viral infections in Sub-Saharan Africa: A review.

The burden of malignancy related to viral infection is increasing in Sub-Saharan Africa (SSA). In 2018, approximately 2 million new cancer cases worldwide were attributable to infection. Prevention or treatment of these infections could reduce cancer cases by 23% in less developed regions and about 7% in developed regions. Contemporaneous increases in longevity and changes in lifestyle have contributed to the cancer burden in SSA. African hospitals are reporting more cases of cancer related to infection (e.g., cervical cancer in women and stomach and liver cancer in men). SSA populations also have elevated underlying prevalence of viral infections compared to other regions. Of 10 infectious agents identified as carcinogenic by the International Agency for Research on Cancer, six are viruses: hepatitis B and C viruses (HBV and HCV, respectively), Epstein-Barr virus (EBV), high-risk types of human papillomavirus (HPV), Human T-cell lymphotropic virus type 1 (HTLV-1), and Kaposi's sarcoma herpesvirus (KSHV, also known as human herpesvirus type 8, HHV-8). Human immunodeficiency virus type 1 (HIV) also facilitates oncogenesis. EBV is associated with lymphomas and nasopharyngeal carcinoma; HBV and HCV are associated with hepatocellular carcinoma; KSHV causes Kaposi's sarcoma; HTLV-1 causes T-cell leukemia and lymphoma; HPV causes carcinoma of the oropharynx and anogenital squamous cell cancer. HIV-1, for which SSA has the greatest global burden, has been linked to increasing risk of malignancy through immunologic dysregulation and clonal hematopoiesis. Public health approaches to prevent infection, such as vaccination, safer injection techniques, screening of blood products, antimicrobial treatments and safer sexual practices could reduce the burden of cancer in Africa. In SSA, inequalities in access to cancer screening and treatment are exacerbated by the perception of cancer as taboo. National level cancer registries, new screening strategies for detection of viral infection and public health messaging should be prioritized in SSA's battle against malignancy. In this review, we discuss the impact of carcinogenic viruses in SSA with a focus on regional epidemiology.

Chemical and Biological Studies of Endophytes Isolated from Marchantia polymorpha.

Natural bioresources, predominantly plants, have always been regarded as the richest source of drugs for diseases threatening humanity. Additionally, microorganism-originating metabolites have been extensively explored as weapons against bacterial, fungal, and viral infections. However, the biological potential of metabolites produced by plant endophytes still remains understudied, despite significant efforts reflected in recently published papers. Thus, our goal was to evaluate the metabolites produced by endophytes isolated from Marchantia polymorpha and to study their biological properties, namely anticancer and antiviral potential. The cytotoxicity and anticancer potential were assessed using the microculture tetrazolium technique (MTT) against non-cancerous VERO cells and cancer cells-namely the HeLa, RKO, and FaDu cell lines. The antiviral potential was tested against the human herpesvirus type-1 replicating in VERO cells by observing the influence of the extract on the virus-infected cells and measuring the viral infectious titer and viral load. The most characteristic metabolites identified in the ethyl acetate extract and fractions obtained by use of centrifugal partition chromatography (CPC) were volatile cyclic dipeptides, cyclo(l-phenylalanyl-l-prolyl), cyclo(l-leucyl-l-prolyl), and their stereoisomers. In addition to the diketopiperazine derivatives, this liverwort endophyte also produced arylethylamides and fatty acids amides. The presence of N-phenethylacetamide and oleic acid amide was confirmed. The endophyte extract and isolated fractions showed a potential selective anticancer influence on all tested cancer cell lines. Moreover, the extract and the first separated fraction noticeably diminished the formation of the HHV-1-induced cytopathic effect and reduced the virus infectious titer by 0.61-1.16 log and the viral load by 0.93-1.03 log. Endophytic organisms produced metabolites with potential anticancer and antiviral activity; thus, future studies should aim to isolate pure compounds and evaluate their biological activities.