Search

This article discusses a case of Powassan virus encephalitis in a 9-year-old boy in Canada. Powassan virus is a tick-borne flavivirus that can cause encephalitis and has a high mortality rate. The boy presented with fever, neck stiffness, and headache after attending a summer camping trip. He experienced neurological symptoms and was eventually diagnosed with Powassan virus encephalitis. The article emphasizes the importance of considering arthropod-borne infections in patients with encephalitis, increasing awareness among clinicians, and reporting cases to public health authorities. [Extracted from the article]

Background: Human herpesvirus 6 (HHV-6) is considered a ubiquitous virus, with many countries reporting a seroprevalence of more than 80–90% among the general population. However, this virus is unique among herpesviruses in its ability to integrate into the genetic material of the host's cells. Thus, there are three ways by which HHV-6 can cause an active infection–primary infection, reactivation of a latent acquired infection, or activation of iciHHV-6 (inherited chromosomally integrated HHV-6). Whole blood quantitative polymerase chain reaction (qPCR) is very useful in distinguishing between iciHHV-6 and primary infection/reactivation. Our aim is to assess the role of HHV-6 in the aetiology of central nervous system (CNS) infections in adults and children, to describe all HHV-6-positive cases in an attempt to determine the susceptible population and to identify potential risk factors that can be linked to HHV-6 meningoencephalitis. Methods: We performed a retrospective study involving patients that were admitted to Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania, with a diagnosis of meningitis or encephalitis. We only selected the clinical records of patients that had a multiplex PCR Biofire® FilmArray® meningitis/encephalitis panel. Results: We report a 5% HHV-6 positivity in the cerebrospinal fluid (CSF) of patients with CNS infections tested with a commercial multiplex PCR M/E (meningitis/encephalitis) panel. Additionally, 2% to 4% of the total study population (n = 100) had active HHV-6 infections, which denotes 40 to 80% of the HHV-6-positive samples. We did not observe any statistically significant correlation between HHV-6 positivity in the CSF and variables such as age, sex, or comorbidities, including obesity, diabetes, hypertension, immunosuppression, or oncologic disease. Therefore, no risk factors could be linked with HHV-6 positivity in the CSF. Conclusions: although multiplex qualitative PCR is highly useful for providing rapid results and identifying nearly every pathogen that can cause meningitis/encephalitis, we have to be aware of this type of test's limitations. All patients with HHV-6 detectable in their CSF via a multiplex PCR test should also undergo qPCR testing from both CSF and blood to prevent over-diagnosing HHV-6 CNS infections, to avoid unnecessary antiviral treatments, and ensure the accurate identification of the true diagnosis. [ABSTRACT FROM AUTHOR]

Deficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6 or JC virus. Herein we perform extensive characterization of the phenotype and functional profile of posoleucel to illustrate the cellular properties that may contribute to its in vivo activity. Our results demonstrate that posoleucel is enriched for central and effector memory CD4+ and CD8+ T cells with specificity for posoleucel target viruses and expressing a broad repertoire of T cell receptors. Antigen-driven upregulation of cell-surface molecules and production of cytokine and effector molecules indicative of proliferation, co-stimulation, and cytolytic potential demonstrate the specificity of posoleucel and its potential to mount a broad, polyfunctional, and effective Th1-polarized antiviral response upon viral exposure. We also show the low risk for off-target and nonspecific effects as evidenced by the enrichment of posoleucel in memory T cells, low frequency of naive T cells, and lack of demonstrated alloreactivity in vitro. The efficacy of posoleucel is being explored in four placebo-controlled clinical trials in transplant recipients to treat and prevent viral infections (NCT05179057, NCT05305040, NCT04390113, NCT04605484). [ABSTRACT FROM AUTHOR]

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. Results: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133–595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. Conclusion: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children. [ABSTRACT FROM AUTHOR]

In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional chemotherapy. In a prospective observational study, we assessed the frequency of and clinical impact of viraemia with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, human herpesvirus-6 (HHV6) and herpes-simplex virus 1/2 (HSV1/2) in paediatric cancer patients at diagnosis, at a routine examination during intensive chemotherapy, and during febrile neutropenia (FN). Seventy-nine patients (median age 6 years; 66 children with haematological malignancies) were included in the study. Overall, 362 blood samples were analysed, 72 from the time at diagnosis (11.1% with positive PCR result), 118 during a regular control after chemotherapy (11.0% positive), and 159 during FN (8.8% positive). The overall positivity rate was 9.6% (CMV 3.3%, HHV6 2.7%, HSV 2.2%, EBV 0.8% and adenovirus 0.3%). There were no significant differences between FN episodes with and without viraemia in terms of duration of fever or neutropenia/lymphopenia, severity of mucositis (> II0), incidence of diarrhea and ICU admission. Our results indicate that viraemia in paediatric cancer patients generally does not have a major clinical impact, and may help in the decision regarding the indication of routine evaluation for viraemia in febrile neutropenic, but otherwise asymptomatic children. [ABSTRACT FROM AUTHOR]

Leukocytosis in neonates can occur because of infectious, inflammatory, malignant, or physiological processes. Hyperleukocytosis is defined as a total leukocyte count (TLC) exceeding 100,000 per mm3, warranting immediate evaluation. Neonates with hyperleukocytosis are at risk of leukostasis and the associated severe complications, including respiratory distress, myocardial ischemia, hyperuricemia, acute renal failure, infarction, and hemorrhage. Differentiating leukemia and leukemoid reactions in neonates presenting with elevated TLC is challenging but critical. We present a unique case of a preterm male neonate with hyperleukocytosis, initially suspected to have an underlying malignancy. The neonate's clinical course was complicated by respiratory distress syndrome and anemia of prematurity, necessitating neonatal intensive care unit management. Further investigation revealed high human herpesvirus 6 (HHV-6) DNA levels in the whole blood, leading to a chromosomally integrated HHV-6 (ciHHV-6) diagnosis. CiHHV-6 is characterized by HHV-6 DNA integration into the host genome. Accurate diagnosis relies on whole-blood quantitative PCR, distinguishing ciHHV-6 from an active infection. The neonate remained asymptomatic, and antiviral treatment was deemed unnecessary. This case underscores the importance of recognizing ciHHV-6 as a potential cause of hyperleukocytosis in neonates and highlights the value of whole-blood PCR for differentiation. Understanding the spectrum of HHV-6 infection in neonates is vital for appropriate management and prognostication. [ABSTRACT FROM AUTHOR]

Recent studies have focused on the role of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) in PR etiology with varying results. In our study, with the approach that the discrepancy between the results may be related to the different samples and techniques used, we aimed to clarify the etiology by examining tissue and plasma samples using molecular methods and evaluating the results together with serological parameters. Skin biopsies and plasma samples of twenty-five PR patients were tested to detect HHV-6 and HHV-7 DNA using calibrated quantitative real-time polymerase chain reaction (CQ RT-PCR). IgG and IgM antibodies against HHV-6 and HHV-7 were tested by enzyme-linked immunosorbent assay and indirect immunofluorescence. Of the patient group, 64% were positive for HHV-6 IgG without IgM positivity. HHV-6 DNA was present in seven tissue and ten plasma samples. HHV-7 positivity was 100% and 12% for IgG and IgM antibodies, respectively. HHV-7 DNA was detected in four tissue samples and one plasma sample. Patients with HHV-7 DNA-positive plasma and tissue samples had also HHV-7 IgM antibodies. In conclusion, our results seem to support the role of HHV-6/HHV-7 in the etiology of PR. To clarify the etiology of PR and avoid confusion, the collection of different biological materials simultaneously and the usage of CQ RT-PCR as a diagnostic technique are recommended. [ABSTRACT FROM AUTHOR]

The rapid and broad microbiological diagnosis of meningoencephalitis (ME) has been possible thanks to the development of multiplex PCR tests applied to cerebrospinal fluid (CSF). We aimed to assess a new multiplex PCR panel (the QIAstat-Dx ME panel), which we compared to conventional diagnostic tools and the Biofire FilmArray ME Panel. The pathogens analyzed using both methods were Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae, Enterovirus, herpes simplex virus 1–2, human herpesvirus 6, human parechovirus, varicella zoster virus, and Cryptococcus neoformans/gattii. We used sensitivity, specificity, PPV, NPV, and kappa correlation index parameters to achieve our objective. Fifty CSF samples from patients with suspected ME were included. When conventional methods were used, 28 CSF samples (56%) were positive. The sensitivity and specificity for QIAstat-Dx/ME were 96.43% (CI95%, 79.8–99.8) and 95.24% (75.2–99.7), respectively, whereas the PPV and NPV were 96.43% (79.8–99.8) and 95.24% (75.1–99.7), respectively. The kappa value was 91.67%. Conclusions: A high correlation of the QIAstat-Dx ME panel with reference methods was shown. QIAstat-Dx ME is a rapid-PCR technique to be applied in patients with suspected ME with a high accuracy. [ABSTRACT FROM AUTHOR]

Background Reasons for the high prevalence of Kaposi sarcoma–associated herpesvirus (KSHV) in sub-Saharan Africa, and risk factors leading to viral reactivation and shedding, remain largely undefined. Preliminary studies have suggested that schistosome infection, which has been associated with impaired viral control, is associated with KSHV. In this study we sought to determine the relationship between active Schistosoma mansoni or Schistosoma haematobium infection and KSHV shedding. Methods We quantified KSHV DNA in saliva and cervical swabs from 2 cohorts of women living in northwestern Tanzanian communities endemic for S mansoni or S haematobium by real-time polymerase chain reaction. χ2 and Fisher exact tests were used to determine differences in clinical and demographic factors between those who were and were not shedding KSHV. Results Among 139 total women, 44.6% were KSHV seropositive. Six percent of those with S mansoni and 17.1% of those with S haematobium were actively shedding KSHV in saliva and none in cervical samples. Women from the S mansoni cohort who were shedding virus reported infertility more frequently (80% vs 19.5%, P =.009). There was no difference in frequency of KSHV salivary shedding between schistosome-infected and -uninfected women. Conclusions In an area with high KSHV seroprevalence and endemic schistosome infections, we provide the first report with data demonstrating no association between schistosome infection and salivary or cervical herpesvirus shedding. KSHV salivary shedding was associated with infertility, a known effect of another herpesvirus, human herpesvirus 6. [ABSTRACT FROM AUTHOR]

Background and Aims: Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV‐6, JCV, and BKV. Objective: Evaluation of EBV, CMV, HHV‐6 ,and JCV, BKV frequency among gastric cancer patients. Methods: In this cross‐sectional study, a total number of 60 gastric cancer specimens (32 male, 28 female) were retrieved from the pathology lab. Formalin‐fixed paraffin‐embedded tissue was used for molecular testing. DNA was extracted from samples, according to protocol, and used for PCR reaction. Polymerase chain reactions were used to assess CMV, EBV, HHV‐6, JCV, and BKV frequency. Results and Conclusion: The mean age of the participants was 61 years and 53.3% (32) of the participants were Male. A total number of 5 samples (8.34%) were infected with viral agents. Four male gastric samples were infected with EBV (6.67%) and only one female sample contained the BKV genome (1.67%). Totally 8.34% of the samples were infected with EBV and BKV. The CMV, HHV‐6, and JCV genome was not detected in the samples. In conclusion, the presence of two viral agents including EBV and BKV among male and female samples respectively, and the genome of other viruses were not detected. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses a rare condition called Frosted Branch Angiitis (FBA) that can affect the retina. FBA is characterized by white perivascular sheathing of retinal vessels, resembling frosted tree branches. The exact cause of FBA is not well understood, but it is believed to be immune-mediated and can be associated with various systemic inflammatory or infectious diseases. The letter presents a case of FBA in an otherwise healthy adult following COVID-19, highlighting the potential ocular complications of the virus. The authors emphasize the importance of considering recent COVID-19 infection or vaccination when evaluating patients with retinal vasculitis. [Extracted from the article]

Abstract Background Human herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series. Case Presentation In this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively. Conclusion This case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

Background: The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized treatment outcomes in patients with lymphoid malignancies. However, several studies have reported a relatively high rate of infection in adult patients following CD19-targeting CAR T-cell therapy, particularly in the first 28 days. Notably, acute human herpesvirus 6 B (HHV6B) reactivation occurs in up to two-thirds of allogeneic hematopoietic stem cell transplantation patients. Case presentations: Herein, we describe a report of HHV6B encephalitis/myelitis in three patients with relapsed/refractory diffuse large B-cell lymphoma post CAR T-cell therapy. All three patients received multiple lines of prior treatment (range: 2–9 lines). All patients presented with fever that persisted for at least 2 weeks after CAR-T cell infusion (CTI). Both the onset time and duration were similar to those of the cytokine release syndrome (CRS); nevertheless, the CRS grades of the patients were low (grade 1 or 2). Delirium and memory loss after CTI were the earliest notable mental presentations. Neurological manifestations progressed rapidly, with patients experiencing varying degrees of impaired consciousness, seizures, and coma. Back pain, lumbago, lower limb weakness and uroschesis were also observed in Patient 3, indicating myelitis. High HHV6B loads were detected in all Cerebral spinal fluid (CSF) samples using metagenomic next-generation sequencing (mNGS). Only one patient required high-activity antivirals and IgG intravenous pulse treatment finally recovered, whereas the other two patients died from HHV6B encephalitis. Conclusion: Considering its fatal potential, HHV6B encephalitis/myelitis should be urgently diagnosed post CAR-T cell-based therapy. Furthermore, hematologists should differentially diagnose these conditions from CRS or other immunotherapy-related neurotoxicities as early as possible. The results of this study demonstrate the potential of mNGS in the early diagnosis of HHV6B infection, particularly when the organism is difficult to culture. [ABSTRACT FROM AUTHOR]

Background: Human herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series. Case Presentation: In this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively. Conclusion: This case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient. [ABSTRACT FROM AUTHOR]

Background and Objectives: Pathogen reduction (PR) technology may reduce the risk of transfusion‐transmitted infections (TTIs), notably transfusion‐transmitted bacterial infection (TTBI) associated with platelet concentrates (PCs). PR (amotosalen/UVA treatment) was implemented for all PCs transfused in France in November 2017. No bacterial detection was in place beforehand. The study aimed to assess the impact of PR PC on TTI and TTBI near‐miss occurrences. Materials and Methods: TTI and TTBI near‐miss occurrences were compared before and after 100% PR implementation. The study period ran from 2013 to 2022. Over 300,000 PCs were transfused yearly. Results: No PC‐related transmission of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and human T‐cell lymphotropic virus was reported throughout the study period. PC‐mediated hepatitis E virus and hepatitis A virus infections occurred irrespective of PR implementation. Mean PC‐mediated TTBI occurrence before PR‐PC implementation was 3/year (SD: 1; n = 15; 1/92,687 PC between 2013 and 2016) with a fatal outcome in two patients. Since PR implementation, one TTBI has been reported (day 4 PC, Bacillus cereus) (1/1,645,295 PC between 2018 and 2022; p < 0.001). Two PR PC quarantined because of a negative swirling test harboured bacteria: a day 6 PC in 2021 (B. cereus and Staphylococcus epidermidis) and a day 7 PC in 2022 (Staphylococcus aureus). Five similar occurrences with untreated PC were reported between 2013 and 2020. Conclusion: Transfusion of 100% PR PC resulted in a steep reduction in TTBI occurrence. TTBI may, however, still occur. Pathogen‐reduced PC‐related TTI involving non‐enveloped viruses occurs as well. [ABSTRACT FROM AUTHOR]

Background and Objectives: Infectious agents are considered one of the possible etiological factors of systemic lupus erythematosus (SLE). It has been suggested that human herpesvirus type 6 (HHV-6) may trigger autoimmune disorders, but few studies have been conducted on the relationship between this virus and autoimmune diseases, especially SLE. The present study aimed to compare the frequency of HHV-6 infection between SLE patients and healthy individuals. Materials and Methods: Serum samples were collected from 60 healthy people and 60 SLE patients referred to the rheumatology clinic of Shahid-Beheshti Hospital, Kashan, Iran, from January 2020 to January 2021. The following data were collected from the medical records of patients: sex; age; duration of disease; SLE clinical manifestations; and disease activity. After the extraction of viral DNA from samples, a nested polymerase chain reaction (PCR) test was performed to detect HHV-6. Results: HHV-6 was detected in 12 SLE patients (20%) and in 8 healthy individuals (13.3%). A significant correlation was not obtained between SLE and the presence of HHV-6 (P = 0.09). There was no correlation between musculoskeletal involvements, skin lesions, renal manifestations, and hematological manifestations with the presence of HHV-6 (P˃0.05). HHV-6 was detected more frequently in patients with active lupus than in patients with quiescent disease, but this difference was not significant (P=0.08). Conclusion: Although patients with SLE had a higher prevalence of HHV-6 compared with healthy people, there is no strong link between HHV-6 infection and SLE. Future research is necessary because this data does not support the hypothesis that human herpesvirus 6 plays a role in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

The complexity of autoimmunity initiation has been the subject of many studies. Both genetic and environmental factors are essential in autoimmunity development. Among others, environmental factors include infectious agents. HHV-6 is a ubiquitous human pathogen with a high global prevalence. It has several properties suggestive of its contribution to autoimmunity development. HHV-6 has a broad cell tropism, the ability to establish latency with subsequent reactivation and persistence, and a range of immunomodulation capabilities. Studies have implicated HHV-6 in a plethora of autoimmune diseases—endocrine, neurological, connective tissue, and others—with some studies even proposing possible autoimmunity induction mechanisms. HHV-6 can be frequently found in autoimmunity-affected tissues and lesions; it has been found to infect autoimmune-pathology-relevant cells and influence immune responses and signaling. This review highlights some of the most well-known autoimmune conditions to which HHV-6 has been linked, like multiple sclerosis and autoimmune thyroiditis, and summarizes the data on HHV-6 involvement in autoimmunity development. [ABSTRACT FROM AUTHOR]

Background: Human herpesvirus 6 (HHV-6) is a double-stranded DNA virus well established in the clinical literature to cause the near-universal childhood infection roseola infantum (exanthema subitum/sixth disease). Primary HHV-6 infection has been reported to cause meningoencephalitis in pediatric patients, although generally in the immunocompromised. Case Description: The authors treated an immunocompetent 18-month-old female who transferred to our institution for a higher level of care given concerns for meningitis in the setting of decreased level of arousal (Glasgow Coma Scale 12), and bradycardia 9 days after the onset of nasal congestion, fatigue, and repeated bouts of emesis. Outside hospital cerebrospinal fluid (CSF) studies were notable for hypoglycorrhachia, elevated protein, elevated nucleated cells with a mononuclear predominance, and a meningitis polymerase chain reaction panel that was positive only for HHV-6. Brain magnetic resonance imaging with and without contrast revealed a basal cistern predominant leptomeningeal enhancement pattern as well as moderate ventriculomegaly with associated periventricular edema concerning acute communicating hydrocephalus. Considering the CSF studies, neuroimaging, and recent travel history to Mexico, central nervous system (CNS) tuberculosis (TB) was the leading suspicion, and antimicrobial therapy was initiated for this presumptive diagnosis with culture data only proving the TB suspicion correct after nearly 2 months in culture. Anti-viral therapy was initially not felt to be necessary as the HHV-6 was interpreted as incidental and not a cause of symptomatic meningitis in our immunocompetent host. The patient's hydrocephalus was treated with temporary CSF diversion followed by performance of an endoscopic third ventriculostomy. Despite appropriate hydrocephalus management, clinical improvement ultimately seemed to correlate with the initiation of antiviral therapy. Conclusion: The authors present this case and review the literature on HHV-6-associated CNS infections with the goal of informing the neurosurgeon about this often clinically underestimated pathogen. [ABSTRACT FROM AUTHOR]

Copyright of Current Neurology / Aktualno?ci Neurologiczne is the property of Medical Communications Sp. z o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses the use of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis. It explains that myocarditis is an inflammatory disease of the myocardium and that endomyocardial biopsy is used to confirm the diagnosis and identify the underlying cause. The article summarizes a study that compared immunosuppressive therapy to conventional therapy in patients without cardiotropic viral infection. The study found that 5-year transplant-free survival was similar in both groups, and biventricular function and NYHA class were also comparable. The article emphasizes the importance of individualizing treatment based on the type and severity of myocarditis and the patient's response and tolerance, and recommends a multidisciplinary team approach for management. Further research is needed to determine the safety and effectiveness of immunosuppressive treatment in patients with myocarditis and viral presence. [Extracted from the article]

A case study of a 16-year-old girl presenting with a widespread skin eruption preceded by a flu-like illness. Topics include differential diagnoses, such as viral exanthems, urticaria, and Sweet syndrome, and the correct diagnosis of erythema multiforme, characterized by symmetrical, targetoid lesions with concentric rings of color variation.

Aims: The association of human herpesvirus 6 (HHV-6) species with pancreatic cancer is controversially discussed. The aim of this study was to further investigate the postulated association and to identify the basis of HHV-6 DNA positivity reported for pancreatic cancer tissue. Methods: All samples of patients with pancreatic cancer (cancer and surrounding tissue) were analyzed for presence of HHV-6 DNA by PCR and then selected cases by immunohistochemistry. Results: Sixty eight per cent (68% = 52/77) of all patients were HHV-6 DNA positive in any of the samples, 49% (38/77) were positive in tumor tissue. Specimens of just one patient were HHV-6A DNA positive, all other patients were positive for HHV-6B. Immunohistochemical analysis of HHV-6 DNA positive samples did not reveal any specific HHV-6B protein positive tumor cell. In contrast, supposed immune cells presented intra- and peritumorally expressed HHV-6B-protein. The cause of presence of these cells in the tumor stroma is unknown, as of yet. Conclusions: HHV-6 DNA-positivity of pancreatic cancer tissue described by us and others is probably not due to the infection of pancreatic cells by HHV-6, but rather due to the migration of HHV-6 positive immune cells into the pancreas. Based on our data, we suppose that there is no direct evidence for HHV-6 as a causative agent of pancreatic cancer, but further in-depth studies (including investigation of immune status of patients) are necessary to make definitive conclusions. [ABSTRACT FROM AUTHOR]

Objective: Inflammatory bowel disease (IBD) is closely related to stress and fatigue. Human herpesvirus 6B (HHV‐6B) is reactivated by stress and fatigue and is associated with IBD. This study aimed to clarify the relationship between IBD and HHV‐6B. Methods: Antibody titers to SITH‐1, a protein specific to HHV‐6B latent infection, were measured in 163 patients with IBD (107 with ulcerative colitis [UC] and 56 with Crohn's disease [CD]); clinical and endoscopic scores and depression scores of UC and CD were analyzed to examine the relationship between SITH‐1 and IBD. The SITH‐1 cut‐off value was set as 1.96, according to known reports. Results: In patients with UC, C‐reactive protein (CRP) level was significantly higher (1.5 vs 0.6 mg/L, P = 0.006) and disease exacerbation within 6 months after entry was significantly more common in the SITH‐1 (+) group (20% vs 0%, P < 0.001). In the subanalysis comparing with and without UC exacerbation, the optimal cut‐off value for SITH‐1 to detect UC exacerbation was 3.44 (area under the curve: 0.81; 95% confidence interval: 0.72–0.90). CRP levels, SITH‐1 levels, and disease activity scores by the clinical or endoscopic index were significantly higher in the exacerbation group than in the non‐exacerbation group (2.6 vs 0.9 mg/L, P = 0.03; 4.90 vs 1.71, P < 0.001; 4 vs 3, P = 0.03; 5 vs 3, P = 0.02; respectively). Conclusion: Patients with UC with high titers of SITH‐1 have high disease activity and frequent disease exacerbation. SITH‐1 can be associated with UC disease activity. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been associated with multiple sclerosis (MS). Teriflunomide is an oral disease- modifying therapy approved for treatment of relapsing forms of MS. In the preclinical Theiler's murine encephalitis virus model of MS, the drug demonstrated an increased rate of viral clearance versus the vehicle placebo. Furthermore, teriflunomide inhibits lytic EBV infection in vitro. Objective: 1. To evaluate the humoral response against EBV and HHV-6 prior to teriflunomide treatment and 6 months later. 2. To correlate the variation in the humoral response against EBV and HHV-6 with the clinical and radiological response after 24 months of treatment with teriflunomide. 3. To analyze the utility of different demographic, clinical, radiological, and environmental data to identify early biomarkers of response to teriflunomide. Methods: A total of 11 MS patients (62 women; mean age: 43.4 years) with one serum prior to teriflunomide onset and another serum sample 6 months later were recruited. A total of 8 had been treated for at least 24 months, 13 had stopped teriflunomide before 24 months, and 8 were currently under teriflunomide therapy but with less than 24 months of follow-up. We analyzed the levels of the viral antibodies titers abovementioned in serum samples with ELISA commercial kits, and the levels of serum neurofilament light chain (Nf-L). Results: Antiviral antibody titers decreased for EBNA-1 IgG (74.3%), VCA IgG (69%), HHV-6 IgG (6.4%), and HHV-6 IgM (73.3%) after 6 months of teriflunomide. VCA IgG titers at baseline correlated with Nf-L levels measured at the same time (r = .221; p = .28) and 6 months later (r = .24; p = .17). We found that higher EBNA-1 titers (p = .1) and a higher age (p = .4) at baseline were associated with NEDA-3 conditions. Thus, 77.8% of patients with EBNA-1 >23. AU and >42.8 years (P5 values) were NEDA-3. Conclusion: Treatment with teriflunomide was associated with a reduction of the levels of IgG antibody titers against EBV and HHV-6. Furthermore, higher EBNA-1 IgG titers prior to teriflunomide initiation were associated with a better clinical response. [ABSTRACT FROM AUTHOR]

Hepatitis is an inflammation of the liver whose etiology is very heterogeneous. The most common cause of hepatitis is viral infections from hepatotropic viruses, including hepatitis A, B, C, D and E. However, other factors such as infections from other agents, metabolic disorders, or autoimmune reactions can also contribute to hepatitis, albeit to a lesser extent. On April 5, 2022, the United Kingdom Health Security Agency alerted the World Health Organization (WHO) on the increased incidence of severe acute hepatitis of unknown causes (not AE) in previously healthy young children, with symptoms of liver failure that in some cases required liver transplantation. By July 2022, 1,296 cases were reported in 37 countries. Acute hepatitis of unknown causes is not an exceptional phenomenon: in fact, it represents more than 30% of cases of acute hepatitis in children, however in the present instance the large proportion of severe cases was surprising and alarming (6% of liver transplants and almost 3% mortality). Multiple hypotheses have been proposed to explain the etiology of such higher proportion of acute hepatitis, including their co-occurrence in the context of COVID-19 pandemic. This is a review of the history of a clinical threat that has put in check a world health care system highly sensitized by the current COVID-19 pandemics, and that it looks like has ended with the arguments that the severe acute pediatric hepatitis is caused by Adeno-associated virus 2 (AAV2) infection associated with a coinfection with a helper virus (human Adenovirus HAdV or human herpesvirus 6) in susceptible children carrying HLA-class II antigen HLA-DRB1*04:01. [ABSTRACT FROM AUTHOR]

During the COVID‐19 pandemic, two further novel viral epidemics were described in 2022, monkeypox virus infections in men having sex with men and non‐A to E hepatitis in children. The latter occurred in the first half of 2022 with about 1000 cases worldwide, necessitating liver transplantation in 5% and causing death in 2% of patients. It took some effort to clarify the cause of the novel hepatitis epidemic. Researchers were confronted with a polymicrobial viral infection consisting of an adenovirus‐associated virus type 2 (AAV2) infection, co‐occurring with either human adenovirus type 41 (HAdV41) or herpesvirus infections; most prominently human herpesvirus type 6 (HHV‐6). AAV‐2, a small Dependovirus of the Parvovirus family, needs these helper viruses for its replication. AAV2 is used as a vector for liver‐targeting gene therapy but was not previously known to cause acute hepatitis. HAdV41 and HHV‐6 are mostly known to cause diarrhoea and febrile illnesses associated with skin rashes in children, respectively. Except for a few case reports of HHV‐6 hepatitis, HAdV and HHV‐6 are mostly known as major pathogens in immunosuppressed transplantation patients. A potential role of SARS‐CoV‐2 has also been discussed but the most popular hypothesis involves an indirect role of the COVID‐19 pandemic for this novel disease. Exposure to HHV‐6 infections occurs nearly quantitatively during the first year of life. Social distancing measures, followed by the lifting of these measures in 2022 might have caused a delayed exposure to multiple, normally benign childhood viral infections eliciting a dysregulated immune response with pathological effects for liver cells. In the fall of 2022, when these conditions were not longer met, case numbers dwindled. The hypothesis of an unequilibrated immune response instead of intrinsic cytopathic activity of the implicated viruses is further supported by the enrichment of a particular HLA allele in cases over controls. [ABSTRACT FROM AUTHOR]

TANGO2 deficiency disorder is a rare genetic disease caused by biallelic defects in TANGO2 gene. We report the clinical phenotype of two children with TANGO2 deficiency disorder. Patient 1 is a female child presenting with developmental delay and microcephaly during the second year of life, who evolved with severe cognitive impairment, facial dysmorphisms, spastic paraparesis, and atonic seizures. At age 13 years, she was hospitalized due to an episode of rhabdomyolysis complicated with cardiac arrhythmia and hypothyroidism. Patient 2 is a female child with dysmorphic facial features, cleft palate, and developmental delay who was diagnosed with DiGeorge syndrome. At age three years, she presented with an acute episode of severe rhabdomyolysis in the context of human herpesvirus 6 infection. After the resolution of this acute episode, she maintained recurrent muscle weakness with axial hypotonia and progressive spasticity of the lower extremities. In both patients, diagnosis of TANGO2 deficiency disorder was only confirmed after an acute metabolic crisis. A high index of suspicion for TANGO2 deficiency disorder is needed in patients with developmental delay or other neurological symptoms and episodic rhabdomyolysis. [ABSTRACT FROM AUTHOR]

Benign acute childhood myositis (BACM) is a self-limited childhood illness, and viral infections mainly cause it. Clinical and laboratory alterations usually normalize rapidly; generally, the only medical intervention required is supportive (hydration and analgesic medication). The low awareness about BACM often led to delayed diagnosis and unneeded ancillary investigations. This study aims to better characterize the clinical and laboratory features of BACM to improve the diagnostic process and inpatient and outpatient management. We conducted a retrospective study selecting all children admitted to Meyer's Children's Hospital-IRCCS (Florence, Italy) with a diagnosis of BACM over the last 5 years, both those visited at Emergency Department (ED) and those admitted to the Pediatric Unit. Clinical, laboratory, and instrumental data were collected from electronic clinical records and analyzed. Overall, sixty-five patients were enrolled; 49 children were visited and discharged directly from ED, whereas 16 were admitted in the Pediatric or Neurologic Wards. The median age was 6.56 years (IQR 4.9–9.1). Male gender (66.1%) and Caucasian ethnicity (70%) were prevalent. Most patients were admitted during winter, and a second peak was found in autumn. All patients had bilateral calf pain, most of them (87.7%) associated with asthenia and refuse to walk (93.8%). Prodromal symptoms were fever (75.3%), cough (32.3%), coryza (26.1%), sore throat (26.1%), and vomiting (15.3%). The median value of CPK was 1827 U/L (IQR 915.5–2462) at peak. CPK median time to normalization was 7 days (IQR 7–8.5) from the nadir. Influenza B was the virus most frequently BACM associated, followed by Influenza A; a novel association with Sars-CoV-2 has been detected. Two patients had pathogenic variants at the Next Generation Sequencing myopathies panel. Conclusion: School-aged children admitted to the hospital with walking difficulty and myalgia, generally after an upper respiratory tract infection with a moderate CPK elevation, should remind at first of BACM. Rapid complaint resolution and biochemical markers normalization will prevent unnecessary tests and inappropriate therapies. What is Known: • BACM is a self-limited syndrome associated with acute infections. Influenza A and B viruses are the main etiological agents, but BACM may be related to many other microorganisms like Parainfluenza virus, Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, Respiratory syncytial virus, Coxsackieviruses, Mycoplasma pneumoniae, Streptococcus pyogenes, Legionella, and Salmonella spp. • Clinical and laboratory alterations usually normalize rapidly; generally, the only medical intervention required is supportive (hydration, analgesic medication). Evolution in rhabdomyolysis and kidney damage is possible but rarely reported. What is New: • Sars-CoV-2 could be an emerging possible cause of BACM. During and after the Sars-CoV-2 outbreak, virus infection seasonality has changed, and so has BACM seasonality. • Screening tests for muscular and metabolic disorders are recommended in recurrent myositis and/or cases with marked CPK elevation (≥ 5000 U/L). [ABSTRACT FROM AUTHOR]

In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV‐6) and 7 (HHV‐7), parvovirus B19 (B19V), enterovirus (EV), Epstein−Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS‐CoV‐2. Differential diagnosis was carried out on 289 discarded cases by multiplex real‐time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV‐7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV‐6, EV, HAdV, and HCMV‐positive cases were found in children aged 0−4 years and HHV‐7 was most frequent in the 15−39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus‐positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities. [ABSTRACT FROM AUTHOR]

In this article, we discuss a recently published article that demonstrated a novel way of identifying viral pathogens reactivating in human cells to be used as cellular therapy, in this instance chimeric antigen receptor (CAR) T cells. The authors used search engines and databases to identify viruses able to reactivate in T cells and then tested this initially in T‐cell cultures, specifically human herpesvirus 6. This virus was then shown to reactivate infrequently in vitro and in vivo in CAR T cells as a consequence of T‐cell activation. The methodology may be most clinically useful for more frequently reactivating viruses in other types of cellular therapy such as allogenic CAR T cells or induced pluripotent stem cells. [ABSTRACT FROM AUTHOR]

This article discusses the variability of viral reactivations during the recurrence of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). The study focuses on a 68-year-old man with myeloma who experienced recurrences of DRESS induced by bortezomib, a drug used to treat multiple myeloma. The patient had viral reactivations of human herpesvirus 6 (HHV6) and cytomegalovirus (CMV) during the first episode of DRESS, and CMV and Epstein-Barr virus (EBV) reactivations during the second episode. The article suggests that viral reactivations may play a role in the pathogenesis of DRESS and that antiviral treatment may be necessary in severe cases. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Background and purpose: Epstein–Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV‐6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. Methods: In the Ausimmune case–control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV‐6‐ and VZV‐DNA load in whole blood and HHV‐6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein–Barr nuclear antigen (EBNA) IgG, EBV‐DNA load, and other covariates. Results: In 204 FCD cases and 215 matched controls, only HHV‐6‐DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08–4.46, p = 0.03). Only EBNA IgG and HHV‐6‐DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV‐specific IgG concentration modified the association between an MS risk‐related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV‐6‐DNA load (>1.0 × 106 copies/mL). Conclusions: HHV‐6‐DNA positivity and high load (possibly due to inherited HHV‐6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV‐related pathways, there should be additional consideration of the role of HHV‐6 infection. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 9-month-old girl who presented with a non-tender, edematous scaly plaque on her right arm. The child had previously experienced fevers, rhinitis, and loose stools, and her parents had tested positive for COVID-19. The patient had received the Bacillus Calmette-Guérin (BCG) vaccine at 5 months of age, and the authors suspected reactivation of the BCG vaccine at the site of vaccination after the viral illness. Reactivation of BCG vaccination has been reported in the literature, and there are a few reports of COVID-19 infection or vaccinations as a possible catalyst for this phenomenon. Treatment is not required, and the prognosis is favorable. [Extracted from the article]

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) are two complex and multifactorial diseases whose patients experience persistent fatigue, cognitive impairment, among other shared symptoms. The onset of these diseases has also been linked to acute herpesvirus infections or their reactivations. In this work, we re-analyzed a previously-described dataset related to IgG antibody responses to 6 herpesviruses (CMV – cytomegalovirus; EBV – Epstein-Barr virus; HHV6 – human herpesvirus-6; HSV1 and HSV2 – herpes simplex virus-1 and -2, respectively; VZV – varicella-zoster virus) from the United Kingdom ME/CFS biobank. The primary goal was to report the underlying symptomology and its association with herpesvirus IgG antibodies using data from 4 disease-trigger-based subgroups of ME/CFS patients (n = 222) and patients with MS (n = 46). The secondary objective was to assess whether serological data could distinguish ME/CFS and its subgroup from MS using a SuperLearner (SL) algorithm. There was evidence for a significant negative association between temporary eye insight disturbance and CMV antibody concentrations and for a significant positive association between bladder problems and EBV antibody concentrations in the MS group. In the ME/CFS or its subgroups, the most significant antibody-symptom association was obtained for increasing HSV1 antibody concentration and brain fog, a finding in line with a negative impact of HSV1 exposure on cognitive outcomes in both healthy and disease conditions. There was also evidence for a higher number of significant antibody-symptom associations in the MS group than in the ME/CFS group. When we combined all the serological data in an SL algorithm, we could distinguish three ME/CFS subgroups (unknown disease trigger, non-infection trigger, and an infection disease trigger confirmed in the lab at the time of the event) from the MS group. However, we could not find the same for the remaining ME/CFS group (related to an unconfirmed infection disease). In conclusion, IgG antibody data explains more the symptomology of MS patients than the one of ME/CFS patients. Given the fluctuating nature of symptoms in ME/CFS patients, the clinical implication of these findings remains to be determined with a longitudinal study. This study is likely to ascertain the robustness of the associations during natural disease course.

Background: To investigate the aetiology of acute undifferentiated fever (AUF) among children under the age of five in Vietnam. Methods: This prospective study was conducted in the Thai Binh paediatric hospital, between July 2020 and July 2021 among children with AUF at admission. Real-time PCR testing 18 microbial pathogens were done on blood samples. Results: 286 children were included, with median age of 16 months. 64.7% were male. 53.9% were positive for at least one pathogen by PCR. Enterovirus, human herpesvirus 6, adenovirus, and varicella zoster virus PCR were positive for 31.1, 12.6, 1.4, and 1.0% patients, respectively. Other pathogens tested negative by PCR. During the hospital stay, based on clinical criteria 47.2% children secondarily presented with signs of respiratory tract infections, 18.9% had hand, foot and mouth disease, 4.6% had chickenpox. 4.2% presented signs of central nervous system infections, 1.0% had dengue (antigenic test) and 1.0% had signs of gastrointestinal infection. Finally, 23.1% patients presented a fever with or without a rash and no other symptoms and ultimately received a diagnosis of AUF. Conclusion: Real-time PCR of blood is useful for detecting pathogens and diagnosing infectious causes of AUF. Further prospective studies with blood and urine culture testing and PCR investigation of not only blood but also cerebrospinal fluid, throat, and skin samples according to symptoms would be of interest to confirm the predominance of viral infections in children with AUF and to guide therapeutic options. [ABSTRACT FROM AUTHOR]

Background and purpose: Meningitis and encephalitis are potentially life‐threatening diseases that require fast and accurate diagnostics and therapy. The value of polymerase chain reaction (PCR) multiplex testing in clinical practice is still a matter of debate. This study aims to evaluate its benefits and limitations in emergency patients. Methods: We assessed the value of a meningoencephalitis PCR array in the clinical routine of an emergency department. Results: Of 1578 emergency patients who received a lumbar puncture, 43% received it for a clinically suspected central nervous system (CNS) infection. After initial workup for cerebrospinal fluid (CSF) cell count, protein and glucose, a CNS infection was still considered likely in 307 patients. In these patients, further microbiologic workup was performed. A total of 230 samples were examined by PCR and a pathogen was detected in 66 of these samples. In the case of a positive microbiologic result, a comparison between PCR array and standard method was available for 59 samples, which demonstrated an overcall agreement of 80% (n = 47/59). Of interest, exclusively array‐positive results were observed for patients with meningitis found to be positive for Streptococcus pneumoniae; four out of five patients had been treated with antibiotics before the lumbar puncture. In samples with normal CSF cell count only two positive array results were obtained, both for human herpesvirus 6, and these were not clinically relevant. Conclusion: Our data suggest that the array substantially contributes to a detection of pathogens in patients with suspected CNS infection and seems of particular interest in patients with acute bacterial meningitis under empiric antibiotic treatment. In CSF samples with normal cell count, it might be dispensable. [ABSTRACT FROM AUTHOR]

Mumps is the second‐most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing. More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were codetected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks. [ABSTRACT FROM AUTHOR]

Skin rash is one of the most common complications during childhood. Viral agents play an essential role in the development of such symptoms. Present study aims to determine the prevalence and genetic variability of Human Herpesvirus 6 and 7 (HHV‐6 and HHV‐7) infections and their subtypes in children under 5 years of age with skin rash and negative for rubella and measles. We used serum and throat swap samples from 196 children with skin rash and fever. ELISA and IFA tests were performed to detect antibodies against HHV6/7. Sequencing was performed using Sanger sequencing, and BioEdit and MEGA10 software were used for sequence analysis. According to the results, 66% and 40% of cases were positive for HHV‐6 IgM and HHV‐7 IgM, respectively. According to the molecular analysis, HHV‐6 Nested‐PCR was positive in 18% of cases, however, HHV‐7 Nested‐PCR was positive in 7.7% of cases. On the other hand, HHV‐6 IgG and HHV‐7 IgG were positive in 91% and 55% of study cases, respectively. For HHV‐6, we found some genetic variabilities resulting in antigenic changes compared to reference strains. HHV‐7 isolates showed no genetic differentiation and had a stable gene sequence. Based on the results, the detection of some cases of HHV6/7 primary infection and the presence of specific symptoms of roseola in the study population needs continuous evaluation of HHV6/7 frequency and distribution, also genetic variabilities of HHV6. This can pave the way for investigating HHV6 immune evasion and vaccine research and studying the relationship between viral genetic variations and other factors like disease severity. Furthermore, it is necessary to determine the relation between HHV6 genetic changes and latent infection to be considered in possible future vaccines and antiviral drug development. [ABSTRACT FROM AUTHOR]

Objective: It remains unclear whether viral infections interfere with multiple sclerosis (MS) disease progression. We evaluated the prognostic role of antibody responses toward viruses determined at disease onset on long-term disease outcomes.Methods: Humoral immune responses against Epstein-Barr virus (EBV)-encoded nuclear antigen EBNA1, viral capsid antigen (VCA) and early antigen, and toward cytomegalovirus (HCMV), human herpesvirus 6 and measles were investigated in a cohort of 143 patients with MS for their association with long-term disability and inflammation disease outcomes.Results: Median (IQR) follow-up was 20 (17.2-22.8) years. In univariable analysis, increased HCMV levels were associated with a lower risk to Expanded Disability Status Scale 4.0 (HR 0.95; 95% CI 0.91 to 0.99; p=0.03), to develop a secondary progressive MS (HR 0.94; 95% CI 0.90 to 0.99; p=0.02) and to first-line treatment (HR 0.98; 95% CI 0.96 to 0.99; p=0.04). High HCMV IgG levels were associated with a longer time to first-line treatment (p=0.01). Increased immune responses against EBV-VCA were associated with higher risk for first-line (HR 1.45; 95% CI 1.12 to 1.88; p=0.005) and second-line treatments (HR 2.03; 95% CI 1.18 to 3.49; p=0.01), and high VCA IgG levels were associated with shorter time to first-line (p=0.004) and second-line (p=0.02) therapies. EBNA1-specific IgG levels correlated with disease severity (0.17; p=0.04) and with an increased relapse rate during follow-up (relapse rate 1.26; 95% CI 1.03 to 1.56; p=0.02) that remained stable in multivariable analysis.Conclusions: These results indicate that elevated immune responses against HCMV at disease onset have protective effects on long-term disability and inflammation disease outcomes. Our data also indicate that increased immune responses against EBV in early phases may influence long-term disease prognosis. [ABSTRACT FROM AUTHOR]

To investigate viruses in measles‐negative cases, 221 measles‐suspected samples collected in Gyeonggi Province, South Korea were tested using a real‐time PCR assay. Rubella virus was not detected. However, 11 cases of parvovirus B19 (5.0%), 47 cases of human herpesvirus 6 (21.3%), 25 cases of human herpesvirus 7 (11.3%), and one case of co‐infection with parvovirus B19 and human herpesvirus 7 were confirmed, as were eight cases of co‐infection with human herpesvirus 6 and human herpesvirus 7. This study showed that parvovirus B19, human herpesvirus 6, and human herpesvirus 7 should be considered by physicians for the diagnosis of measles‐suspected patients. [ABSTRACT FROM AUTHOR]

Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the chromosomes of the host germ cell and is vertically transmitted. The aims of this study were to identify iciHHV-6 prevalence in hospitalized patients and clinical features in individuals carrying this integration. HHV-6 PCR on hair follicles was used to confirm iciHHV-6 status when the blood viral load was more than 5 Log10 copies/mL. From January 2012 to June 2022, HHV-6 DNAemia was investigated in 2019 patients. In particular, 49 had a viral load higher than 6 Log10 copies/mL and HHV-6 DNA in hair follicles was positive. A viral load between 5.0 and 5.9 Log10 copies/mL was observed in 10 patients: 6 infants with acute HHV-6 infection and 4 patients with leukopenia and HHV-6 integration. Therefore, the iciHHV-6 prevalence in our population was 2.6% (53/2019). Adult patients with integration presented hematological (24%), autoimmune (11%), autoimmune neurological (19%), not-autoimmune neurological (22%), and other diseases (19%), whereas 5% had no clinically relevant disease. Although in our study population a high percentage of iciHHV-6 adult hospitalized patients presented a specific pathology, it is still unknown whether the integration is responsible for, or contributes to, the disease development. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the etiology is still unclear. Some studies have indicated that viral infection might contribute to the development of SLE. Methods: A total of 105 individuals with SLE and 110 matched healthy controls were tested for EBV-specific DNA fragments in peripheral blood monocytes by PCR-Southern blotting. The expression of EBV-encoded genes was determined by RT-PCR and Southern blotting in EBV-positive patients. Serum EBV-specific IgM antibody was determined by ELISA. HHV-6 DNA in peripheral blood monocytes of those SLE patients and normal controls was tested by nested PCR. Results: Statistical analysis showed that the EBV-positive rate of SLE patients was significantly higher than that of the control group (χ2 = 87.329, P = 0), while the difference in the HHV-6-positive rate between the two groups was not significant (P > 0.05). An association of EBV and HHV-6 positivity in SLE patients was found (P = 0, r = 0.38). The EBV IgM level was significantly higher in SLE patients than in healthy controls (χ2 = 25.184, P = 0). Forty-two of the 75 EBV DNA-positive specimens were positive for EBNA2 mRNA, and an association between EBV EBNA2 mRNA and anti-Sm antibody positivity was found (P = 0, r = 0.409). LMP1 mRNA was positive in 2 SLE patients with active phase, and no LMP2A mRNA expression was detected in EBV DNA-positive specimens. EBV early gene BARF1 mRNA was detected in 2 cases of EBV-positive SLE patients, and these 2 patients were also HHV-6 DNA positive. Thirty-eight patients were BcLF1 mRNA positive, and 33 of them were HHV-6 positive as well. These factors were associated (χ2 = 15.734, P = 0). The expression of the EBV immediate early gene BZLF1 was negative in all 75 EBV-positive SLE patients. Conclusions: The results suggest that EBV infection might be related to the occurrence of SLE. Although there is no direct evidence that HHV-6 infection is associated with the development of SLE, EBV and HHV-6 infection may have a coacceleration effect in SLE patients. This study provides a new theoretical and experimental basis for the study of viral etiology and the prevention and treatment of SLE. [ABSTRACT FROM AUTHOR]

Background: Immunocompromised patients face reactivation of latent viruses that increase the risk of morbidity. Aim: The study aimed to detect human herpes virus 6 (HHV-6) reactivation among allogeneic (allo) and autologous (auto) hematopoietic stem cell transplant (HSCT) recipients and to correlate potentially attributed clinical manifestations to HHV-6 DNA plasma level. Methods: A prospective study included all (forty) patients undergoing allo and auto-HSCT from Jan 2020 till June 2022. Plasma samples were collected for HHV-6 serology, and for HHV-6 quantitative PCR at post-transplantation weeks 2, 4, 6. Demographic and clinical data were recorded. Results: Out of 40 peripheral blood stem cell transplant (PBSCT) recipients, 34 (85%) were HHV-6 IgG positive pre-HSCT. Of which, fourteen patients (14/34, 41.2%) showed positive HHV-6 DNaemia. HHV-6 DNAemia (15/40, 37.5%) was significantly higher among allo (8/12, 66.7%) versus auto (7/28, 25%) HSCT recipients (p = 0.030). Patients with HHV-6 DNAemia developed fever, delayed engraftment and bone marrow suppression in 6/15, 40%, thrombocytopenia (5/15, 33.3%), rash and pneumonitis (2/15, 13.3%), acute GVHD (aGVHD) (1/15, 6.7%). HHV-6 DNAemia ranged from 101 to 102,000 copies/mL. Univariate analysis identified conditioning with busulfan–cyclophosphamide as a significant risk (p = 0.043), while receiving BEAM protocol was a protective factor (p = 0.045). In multivariate analysis, receiving BEAM protocol retained significance (p = 0.040). Conclusion: Frequent HHV-6 reactivation was detected after HSCT, especially in allo-HSCT recipients with clinical manifestations which could not be otherwise explained. To our best knowledge this is the first study of HHV6 reactivation in HSCT recipients from Egypt. Raising awareness for HHV-6 reactivation manifestations and screening in HSCT recipients could be lifesaving. [ABSTRACT FROM AUTHOR]

Pseudotumor cerebri (PTC) in children is a rare condition whose underlying cause remains largely unknown. No study has yet systematically examined viral infection as a cause of PTC. The current study aimed to characterize PTC in children and investigate the possible role of acute viral infection of the central nervous system in its pathogenesis. A prospective, cross-sectional study was conducted in three centers in Israel. Participants were 50 children aged 0.5–18 years, of whom 27 had a definitive diagnosis of pseudotumor cerebri (the study group) and 23 comprised a control. Data collected included clinical presentation, imaging, treatment, ophthalmic findings, and cerebrospinal fluid (CSF) analysis. Using the ALLPLEXTM meningitis panel, real-time polymerase chain reaction (PCR) was used to test for the presence of 12 common viruses. PTC patients (mean age 12 ± 4.3 years; 14 males, 13 females) had mean opening pressure of 41.9 ±10.2 mmH2O. All PTC patients had papilledema, and 25 (93%) had PTC symptoms. No viruses were found in the PTC group, while in the control group, one patient tested positive for Epstein–Barr virus and another for human herpesvirus type 6. Overall, in our study, PTC was not found to be associated with the presence of viruses in CSF. [ABSTRACT FROM AUTHOR]

A novel syndrome called long-haul COVID or long COVID is increasingly recognized in a significant percentage of individuals within a few months after infection with SARS-CoV-2. This disorder is characterized by a wide range of persisting, returning or even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine and systemic. Some overlapping symptomatologies exist between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Very much like with long ME/CFS, infections with herpes family viruses, immune dysregulation, and the persistence of inflammation have been reported as the most common pattern for the development of long COVID. This review describes several factors and determinants of long COVID that have been proposed, elaborating mainly on viral persistence, reactivation of latent viruses such as Epstein–Barr virus and human herpesvirus 6 which are also associated with the pathology of ME/CFS, viral superantigen activation of the immune system, disturbance in the gut microbiome, and multiple tissue damage and autoimmunity. Based on these factors, we propose diagnostic strategies such as the measurement of IgG and IgM antibodies against SARS-CoV-2, EBV, HHV-6, viral superantigens, gut microbiota, and biomarkers of autoimmunity to better understand and manage this multi-factorial disorder that continues to affect millions of people in the world. [ABSTRACT FROM AUTHOR]

Simple Summary: The objective of this study was to uncover the association between oral human herpesvirus-6 (HHV-6) and HHV-7 infection and periodontitis. Oral HHV-6 and HHV-7 DNA were analyzed by a real-time polymerase chain reaction using tongue swab samples from 74 older adults. Of the 74 participants, one participant (1.4%) was HHV-6 DNA-positive and 36 participants (48.6%) were HHV-7 DNA-positive. HHV-7 DNA-positive participants had a higher prevalence of diabetes (16.7%) than HHV-7 DNA-negative participants (7.9%). However, there was no significant association between HHV-7 DNA positivity and diabetes. Oral HHV-7 infection was significantly associated with a deep periodontal pocket (p = 0.04). HHV-7 DNA-positive participants had a higher positive rate of a periodontal pocket with BOP (25.0%) than the HHV-7 DNA-negative participants (7.9%). Additionally, the HHV-7 DNA-positive participants had higher PISA values (52.7 mm2) than the HHV-7 DNA-negative participants (47.2 mm2). These results indicate that oral HHV-7 infection is associated with active periodontitis. However, there was no statistically significant association between HHV-7 and a ≥6-mm periodontal pocket with BOP positivity or the PISA value. Oral herpesviruses other than HHV-7 may be more closely associated with periodontitis. It is necessary to clarify the association between HHV-7 and periodontitis with the detection of HHV-7 in the periodontal pocket. Background: The associations between oral human herpesvirus-6 (HHV-6) and HHV-7, periodontal conditions, and lifestyle-related diseases, such as hypertension, diabetes, and dyslipidemia, have not been fully investigated in older adults. Methods: Seventy-four older patients who visited Hiroshima University Hospital were enrolled. Tongue swab samples were employed, and a real-time polymerase chain reaction was performed to detect HHV-6 and HHV-7 DNA. Dental plaque accumulation, probing pocket depth, and bleeding on probing (BOP) (i.e., a sign of periodontal inflammation) were examined. The periodontal inflamed surface area (PISA) value (i.e., an indicator of the severity of periodontitis) was also examined. Results: Of the 74 participants, one participant (1.4%) was HHV-6 DNA-positive and 36 participants (48.6%) were HHV-7 DNA-positive. A significant association between HHV-7 DNA and probing depth was found (p = 0.04). The HHV-7 DNA-positive participants had a higher positive rate of a ≥6-mm periodontal pocket with BOP (25.0%) than the HHV-7 DNA-negative participants (7.9%). Additionally, the HHV-7 DNA-positive participants had a higher PISA value than the HHV-7 DNA-negative participants. However, there was no significant association between HHV-7 and the PISA value (p = 0.82). No significant association was found between HHV-7 and lifestyle-related diseases (p > 0.05). Conclusions: Oral HHV-7 infection is associated with a deep periodontal pocket. [ABSTRACT FROM AUTHOR]