Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study.

Background: Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Aim: Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. Since the occurrence of EBV in saliva during acute infectious diseases has not yet been systematically researched, we aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. Material and methods: This pilot cross-sectional study included consenting adults hospitalized for acute infectious conditions and their peers free of acute infectious diseases. A total of 40 patients with acute infectious diseases were enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. We fitted logit and general linear models to proportions and to ln (viral copy counts) to generate adjusted proportions and geometric mean values in the two groups of subjects. We used SAS for Windows 9.4. Results: The most common acute infectious disease was COVID-19 pneumonia, followed by hemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. Conclusions: The presented preliminary data do not indicate acute infectious conditions as a marked "contributor" in increasing salivary EBV shedding.

Isolation and complete genomic characterization of a Movar 33/63-like Japanese bovine herpesvirus 4 from a calf with respiratory disease.

Bovine herpesvirus 4 (BoHV-4) is an indigenous virus in cattle prevalent mainly in North and South American countries and European countries, but the genomic sequences and genetic characteristics of Japanese strains have not been reported. BoHV-4 is suspected, but not proven, to be associated with various diseases. In the present study, we isolated BoHV-4 from a 10-month-old Japanese Black calf with respiratory symptoms in Japan. To identify the genetic characteristics of the isolate named strain SG20, complete genome sequencing was performed using a combination of next-generation and Sanger sequencing technologies. The complete long unique coding region (LUR) of SG20 was found to comprise 108,819 nucleotides with 41.4% GC content and contain at least 78 open reading frames. It shares 83.4 to 99.3% overall nucleotide identity with six BoHV-4 strains available in the database. The deduced amino acid sequence alignment revealed that SG20 contains genotype 1-specific features of BoHV-4, such as amino acid substitutions and insertions within the glycoprotein B region. Phylogenetic analyzes based on the nucleotide sequences of ORF20 indicated that the virus belonged to genotype 1 (Movar 33/63-like group). The strain was also analyzed using the complete LUR and placed in the same clade as a strain recently isolated from China, but it was distinct from American and European BoHV-4 strains of genotype 1. Although further genomic and epidemiologic information is needed, our results help elucidate the molecular epidemiology of BoHV-4 and provide a foundation for future studies.

Epstein-Barr Virus DNA Is Associated With Conjunctival Squamous Cell Carcinomas: A Case-Control Study From Zimbabwe.

Incidence of conjunctival squamous cell carcinoma (cSCC) in Zimbabwe is >30-fold higher than the global average. cSCC risk is notably higher among people with human immunodeficiency virus, implicating impaired immune response and a yet unknown infectious etiology. Formalin-fixed, paraffin-embedded blocks from Zimbabwe, comprising conjunctival precancer (n = 78), invasive cSCC cases (n = 148) and nonmalignant eye lesions (n = 119), were tested for multiple DNA viruses using Luminex bead-based technology. Epstein-Barr virus (EBV) type 1 positivity was strongly associated with cSCC diagnosis (adjusted odds ratio [aOR], 5.6 [95% confidence interval {CI}, 3.0-10.4) and marginally associated with precancer (aOR, 2.1 [95% CI, 1.0-4.5]). On analyzing EBV transcriptional activity with any of LMP1, EBNA1, and BZLF1, RNA transcripts were detected in 5 of 112 controls, 3 of 67 precancers, and 10 of 139 cases and none were associated with conjunctival case status. Our EBV DNA data suggest that EBV may play a role in cSCC. However, the low detection rate of EBV RNA supports further investigation to infer causality.

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant.

Ovine herpesvirus 2 (OvHV-2) and bovine herpesvirus 4 (BoHV-4) are gamma herpesviruses that belong to the genera Macavirus and Rhadinovirus, respectively. As with all herpesviruses, both OvHV-2 and BoHV-4 express glycoprotein B (gB), which plays an essential role in the infection of host cells. In that context, it has been demonstrated that a BoHV-4 gB-null mutant is unable to infect host cells. In this study, we used homologous recombination to insert OvHV-2 ORF 8, encoding gB, into the BoHV-4 gB-null mutant genome, creating a chimeric BoHV-4 virus carrying and expressing OvHV-2 gB (BoHV-4∆gB/OvHV-2-gB) that was infectious and able to replicate in vitro. We then evaluated BoHV-4∆gB/OvHV-2-gB as a potential vaccine candidate for sheep-associated malignant catarrhal fever (SA-MCF), a fatal disease of ungulates caused by OvHV-2. Using rabbits as a laboratory model for MCF, we assessed the safety, immunogenicity, and efficacy of BoHV-4∆gB/OvHV-2-gB in an immunization/challenge trial. The results showed that while BoHV-4∆gB/OvHV-2-gB was safe and induced OvHV-2 gB-specific humoral immune responses, immunization conferred only 28.5% protection upon challenge with OvHV-2. Therefore, future studies should focus on alternative strategies to express OvHV-2 proteins to develop an effective vaccine against SA-MCF.

Equine herpesvirus 4 infected domestic horses associated with Sintashta spoke-wheeled chariots around 4,000 years ago.

Equine viral outbreaks have disrupted the socio-economic life of past human societies up until the late 19th century and continue to be of major concern to the horse industry today. With a seroprevalence of 60-80 per cent, equine herpesvirus 4 (EHV-4) is the most common horse pathogen on the planet. Yet, its evolutionary history remains understudied. Here, we screen the sequenced data of 264 archaeological horse remains to detect the presence of EHV-4. We recover the first ancient EHV-4 genome with 4.2× average depth-of-coverage from a specimen excavated in the Southeastern Urals and dated to the Early Bronze Age period, approximately 3,900 years ago. The recovery of an EHV-4 virus outside the upper respiratory tract not only points to an animal particularly infected but also highlights the importance of post-cranial bones in pathogen characterisation. Bayesian phylogenetic reconstruction provides a minimal time estimate for EHV-4 diversification to around 4,000 years ago, a time when modern domestic horses spread across the Central Asian steppes together with spoke-wheeled Sintashta chariots, or earlier. The analyses also considerably revise the diversification time of the two EHV-4 subclades from the 16th century based solely on modern data to nearly a thousand years ago. Our study paves the way for a robust reconstruction of the history of non-human pathogens and their impact on animal health.

Investigation of DNA Hybridization on Nano-Structured Plasmonic Surfaces for Identifying Nasopharyngeal Viruses.

Recently, studies have revealed that human herpesvirus 4 (HHV-4), also known as the Epstein-Barr virus, might be associated with the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared to SARS-CoV-2 infection alone, patients coinfected with SARS-CoV-2 and HHV-4 had higher risks of fever, inflammation, and even death, thus, confirming that HHV-4/SARS-CoV-2 coinfection in patients could benefit from clinical investigation. Although several intelligent devices can simultaneously discern multiple genes related to SARS-CoV-2, most operate via label-based detection, which restricts them from directly measuring the product. In this study, we developed a device that can replicate and detect SARS-CoV-2 and HHV-4 DNA. This device can conduct a duplex polymerase chain reaction (PCR) in a microfluidic channel and detect replicates in a non-labeled manner through a plasmonic-based sensor. Compared to traditional instruments, this device can reduce the required PCR time by 55% while yielding a similar amount of amplicon. Moreover, our device's limit of detection (LOD) reached 100 fg/mL, while prior non-labeled sensors for SARS-CoV-2 detection were in the range of ng/mL to pg/mL. Furthermore, the device can detect desired genes by extracting cells artificially infected with HHV-4/SARS-CoV-2. We expect that this device will be able to help verify HHV-4/SARS-CoV-2 coinfected patients and assist in the evaluation of practical treatment approaches.

A prospective evaluation of the diagnostic potential of EBV-DNA in plasma and whole blood.

BACKGROUND: Quantitative polymerase chain reaction (qPCR) for Epstein-Barr virus (EBV)-DNA is an important diagnostic tool for EBV-associated disease, but interpretation of its clinical significance is challenging. OBJECTIVES: We assessed the diagnostic and clinical performance of WHO-standardised qPCR for EBV-DNA (WHO EBV-qPCR) in plasma and whole blood (WB) for proven EBV disease in a prospectively accrued patient cohort. STUDY DESIGN: Central Denmark Region patients, tested with WHO EBV-qPCR from November 2017 to March 2019, were screened for EBV disease. Incidence (IR) was estimated by Poisson regression. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for EBV-qPCR in plasma and WB. Risk of diagnostic latency was compared between patients with EBV-positive and EBV-negative lymphomas. RESULTS: EBV disease was diagnosed in 95 of 1484 participants (IR: 16.3 per 1000 patientyears 95%CI; 13.3-19.9). Sensitivity and specificity of WHO EBV-qPCR in plasma was 82.4% (95% CI; 74.2-90.7%) and 87.8% (95% CI; 85.6-90%), yielding a PPV of 32.2% (95% CI; 24.9-39.5%) and NPV of 98.6% (95% CI; 97.7-99.5%) for proven EBV disease. Sensitivity and NPV were comparable in WB, while specificity and PPV decreased to 66.9% (95% CI; 60.6-73.1%) and 18.1% (95% CI; 7.5-28.7%). Risk of diagnostic latency was 2.3-fold (95% CI 1.4-4.1) higher for patients with EBV-positive compared with EBV-negative lymphomas. CONCLUSIONS: WHO EBV-qPCR in plasma and WB have a low PPV but a high NPV for proven EBV disease. Implementation of WHO EBV-qPCR could improve interpretation and facilitate EBV-positive lymphoma diagnosis.

E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.

For productive infection and replication to occur, viruses must control cellular machinery and counteract restriction factors and antiviral proteins. Viruses can accomplish this, in part, via the regulation of cellular gene expression and post-transcriptional and post-translational control. Many viruses co-opt and counteract cellular processes via modulation of the host post-translational modification machinery and encoding or hijacking kinases, SUMO ligases, deubiquitinases, and ubiquitin ligases, in addition to other modifiers. In this review, we focus on three oncoviruses, Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), and human immunodeficiency virus (HIV) and their interactions with the ubiquitin-proteasome system via viral-encoded or cellular E3 ubiquitin ligase activity.

An attenuated herpesvirus vectored vaccine candidate induces T-cell responses against highly conserved porcine reproductive and respiratory syndrome virus M and NSP5 proteins that are unable to control infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a leading cause of economic loss in pig farming worldwide. Existing commercial vaccines, all based on modified live or inactivated PRRSV, fail to provide effective immunity against the highly diverse circulating strains of both PRRSV-1 and PRRSV-2. Therefore, there is an urgent need to develop more effective and broadly active PRRSV vaccines. In the absence of neutralizing antibodies, T cells are thought to play a central role in controlling PRRSV infection. Herpesvirus-based vectors are novel vaccine platforms capable of inducing high levels of T cells against encoded heterologous antigens. Therefore, the aim of this study was to assess the immunogenicity and efficacy of an attenuated herpesvirus-based vector (bovine herpesvirus-4; BoHV-4) expressing a fusion protein comprising two well-characterized PRRSV-1 T-cell antigens (M and NSP5). Prime-boost immunization of pigs with BoHV-4 expressing the M and NSP5 fusion protein (vector designated BoHV-4-M-NSP5) induced strong IFN-γ responses, as assessed by ELISpot assays of peripheral blood mononuclear cells (PBMC) stimulated with a pool of peptides representing PRRSV-1 M and NSP5. The responses were closely mirrored by spontaneous IFN-γ release from unstimulated cells, albeit at lower levels. A lower frequency of M and NSP5 specific IFN-γ responding cells was induced following a single dose of BoHV-4-M-NSP5 vector. Restimulation using M and NSP5 peptides from PRRSV-2 demonstrated a high level of cross-reactivity. Vaccination with BoHV-4-M-NSP5 did not affect viral loads in either the blood or lungs following challenge with the two heterologous PRRSV-1 strains. However, the BoHV-4-M-NSP5 prime-boost vaccination showed a marked trend toward reduced lung pathology following PRRSV-1 challenge. The limited effect of T cells on PRRSV-1 viral load was further examined by analyzing local and circulating T-cell responses using intracellular cytokine staining and proliferation assays. The results from this study suggest that vaccine-primed T-cell responses may have helped in the control of PRRSV-1 associated tissue damage, but had a minimal, if any, effect on controlling PRRSV-1 viral loads. Together, these results indicate that future efforts to develop effective PRRSV vaccines should focus on achieving a balanced T-cell and antibody response.

Evaluation of a Quantitative Dual-Target EBV DNA Test on a Fully Automated Molecular Testing System.

The measurement of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) is key to diagnosing and managing EBV-associated complications in transplant recipients. The performance of the new Conformité Européenne (CE) and Food and Drug Administration (FDA)-cleared quantitative Roche cobas EBV real-time PCR assay was determined by using EDTA-plasma dilution panels and clinical samples that were spiked with either the World Health Organization's EBV international standard or high-titer EBV lambda stock. Correlation with the Abbott Realtime EBV assay was assessed in clinical specimens and conducted at two independent laboratories. An in silico analysis revealed that the dual-target test (EBNA1 and BMRF2) was 100% inclusive for the known diversity of EBV. The overall limit of detection (LoD) was 16.6 IU/mL for genotype 1 (GT1). GT2 LoD was verified at 18.8 IU/mL. The linear ranges were from 1.40 × 101 to 2.30 × 108 IU/mL and from 2.97 × 101 to 9.90 × 107 IU/mL for GT1 and GT2, respectively. Accuracy was confirmed across the linear range (mean difference not exceeding ±0.18 log10). Precision was not influenced by the factors analyzed (standard deviation of 0.02 to 0.17 log10), including the presence of potentially interfering endogenous or exogenous substances. Plasma samples were stable under several conditions (variable time points, storage, and freeze/thaw cycles). In clinical EBV DNA-positive samples, correlation between the cobas EBV test and the comparator was high (n = 126 valid results; R2 = 0.96) with a 0.1 mean log10 titer difference. The cobas EBV test is an accurate, sensitive, specific, and reproducible assay for the detection of EBV DNAemia in plasma. In general, high levels of automation and calibration to the international standard will lead to improvements in the harmonization of quantitative EBV DNA test results across laboratories.

Serum and Milk Levels of Antibodies to Bovine Viral Diarrhoea Virus, Bovine Herpesvirus-1 and -4, and Circulation of Different Bovine Herpesvirus-4 Genotypes in Dairy Cattle with Clinical Mastitis.

Introduction: Bovine viral diarrhoea virus (BVDV) and bovine herpesvirus (BoHV)-1 and -4 are important causes of respiratory diseases and reproductive disorders of dairy cattle worldwide. Material and Methods: Investigation of BVDV and BoHV-1 and -4 antibody levels in the serum and milk of dairy cattle in a group with clinical mastitis and a healthy group was undertaken using an indirect ELISA, and identification of the BoHV-4 genotypes in clinical mastitis cases was attempted by PCR and sequencing. Results: Antibodies specific to BVDV, BoHV-1 and BoHV-4 were detected in the serum and milk of all dairy cattle with clinical mastitis. The cut-off values for BVDV and BoHV-1 in the sera and milk were extremely high in both healthy and mastitic animals. However, BoHV-4 antibodies were detected only in the clinically mastitic cattle, and BoHV-4 levels were higher in milk than in sera among these animals. Genotypes I and II of BoHV-4 were detected in the milk samples of four seropositive cows with clinical mastitis from the same herd. Conclusion: The results of this investigation demonstrate that clinical mastitis cases in the same herd may have aetiology in different BoHV-4 genotypes.

Viral detection from negative mumps cases with respiratory symptoms in Gwangju, South Korea in 2021.

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.

Diagnostic Value of Whole-Blood and Plasma Samples in Epstein-Barr Virus Infections.

Epstein-Barr virus (EBV) is an oncogenic virus classified by the World Health Organization as a class 1 carcinogen. Post-transplant lymphoproliferative disorders are believed to be strongly related to an EBV infection. Monitoring of EBV DNAemia is recommended to assess the risk of reactivation of latent infection and to assess the effectiveness of therapy. Currently, various types of clinical specimens are used for this purpose. The aim of the study was to assess a reliable method of EBV viral load investigation depending on the clinical material used: whole blood or plasma samples. We found that of 134 EBV-DNA-positive whole-blood samples derived from 51 patients (mostly hemato-oncology or post-transplantation), only 43 (32.1%) were plasma-positive. Of these, 37 (86.0%) had lower plasma DNAemia compared to the corresponding whole-blood samples. We conclude that whole-blood samples have a higher sensitivity than plasma samples in EBV DNA detection. The clinical utility of the tests is unclear, but our results suggest that either whole blood or plasma should be used consistently for EBV viral load monitoring.

A New Insight Into p53-Inhibiting Genes in Epstein­Barr Virus-Associated Gastric Adenocarcinoma

Background: The p53 mutation is uncommon in Epstein­Barr virus-linked gastric carcinoma, but its suppression occurs through mechanisms such as ubiquitin specific peptidase 7 (USP7) inhibitions via Epstein­Barr virus nuclear antigen-1 (EBNA1) activity. This study aimed to evaluate the effect of EBNA1 on p53-inhibiting gene expression and the impact of USP7 inhibition on p53 suppression. Methods: MKN-45 cells were transfected with the EBNA1 plasmid. A stable EBNA1 expression cell line was developed through selection based on hygromycin B resistance. Murine double minute (MDM)4, MDM2, sirtuin (SIRT)3, histone deacetylase (HDAC)1, proteasome 26S subunit, Non-ATPase (PSMD)10, USP7, and p53 expression were checked using real-time PCR. Also, cells containing EBNA1 or control plasmid were treated with GNE-6776, and the expression of the interested genes and cell survival were assessed. Results: MDM4, MDM2, and PSMD10 were significantly upregulated in the MKN-45 cell line following EBNA1 transfection. Morphological changes were observed in the cells harboring EBNA1 after 20 days. In the control cells, USP7 inhibition significantly upregulated the HDAC1, PSMD10, MDM4, and MDM2 genes after 24 h, but downregulated these genes after four days. In the EBNA1-harboring cells, MDM2, MDM4, and PSMD10 genes were significantly upregulated after 24 h, and this effect was sustained for all genes except for MDM4, even after four days. Furthermore, USP7 inhibition induced apoptosis in both cell groups. Conclusion: EBNA1 enhances the expression of p53-inhibiting genes. Two events­p53 protein overexpression and apoptosis activation­followed the suppression of the USP7 protein and provided evidence for its possible function. The significance of the EBNA1-USP7 interaction in p53 suppression warrants additional investigation and possibly reconsideration.

Research progress of primary pulmonary lymphoepithelioma-like carcinoma / 国际肿瘤学杂志

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a distinct type of lung cancer with histological profiles similar to nasopharyngeal carcinoma. The development is associated with EBV and plasma EBV DNA has predictive value in the progression and prognosis of PPLELC. PPLELC is different from some other types of lung cancer in that it has a low mutation rate of the classical lung cancer driver genes and targeted therapy is ineffective for it. Chemotherapy combined with immunotherapy may be the best first-line treatment option for patients with advanced PPLELC.

Epstein-Barr virus in gastric cancer and association with 30 bp del-latent membrane protein 1 polymorphism

SUMMARY OBJECTIVE: This study aimed to determine the frequencies of Epstein-Barr virus, types 1 and 2 infection, and 30 bp del-latent membrane protein 1 viral polymorphism in gastric adenocarcinomas, as well as to investigate the association between Epstein-Barr virus infection and tumor location, type, and the patient's sex. METHODS: Samples were collected from 38 patients treated at a university hospital in Rio de Janeiro, Brazil. Epstein-Barr virus detection and genotyping were performed by polymerase chain reaction, followed by polyacrylamide gel electrophoresis and staining by the silver nitrate method. RESULTS: Overall, 68.4% of patients had Epstein-Barr virus-positive tumors. Of these, 65.4% presented infection by Epstein-Barr virus type 1, 23.1% by Epstein-Barr virus type 2, and 11.5% had coinfection with types 1 and 2. The 30 bp del-latent membrane protein 1 polymorphism was found in 42.3% of Epstein-Barr virus-positive tumors, 23.1% had the wild-type virus, and 23.1% had the wild-type and the polymorphism concomitantly. In 11.5% of Epstein-Barr virus-positive tumors, it was impossible to determine whether there was polymorphism or not. Tumor location in the antrum (22 of 38) and diffuse type (27 of 38) were predominant. There was no significant difference in Epstein-Barr virus infection or the 30 bp del-latent membrane protein 1 polymorphism between men and women. CONCLUSION: Epstein-Barr virus infection was found in 68.4% of tumors investigated in this study. To the best of our knowledge, this is the first article showing the coinfection of Epstein-Barr virus types 1 and 2 in gastric carcinoma in Brazil.

Correlation between peak viral load and liver function damage in children with infectious mononucleosis induced by Epstein-Barr virus / 中国基层医药

Objective:To investigate the relationship between the peak load of Epstein-Barr virus (EPV) and live function damage in children with infectious mononucleosis caused by EPV.Methods:Eighty children with infectious mononucleosis caused by EPV who received treatment in Pingxiang People's Hospital from January 2018 to December 2021 were included in this study. Five mL of venous blood was taken from each child for detecting the peak load of EBV-DNA and liver function indicators. These children were divided into a low-load group ( n = 25, EBV-DNA load < 10 4 copies/mL), a medium-load group ( n = 34, EBV-DNA load of 10 4-10 5 copies/mL), and a high-load group ( n = 21, EBV-DNA load > 10 5 copies/mL) according to the peak EBV-DNA load. The relationships between different peak loads of EBV-DNA and live function, age, and sex were analyzed. Results:The rate of liver dysfunction in the high-load group [85.71% (18/21)] was significantly higher than [38.24% (13/34)] in the medium-load group and [20.00% (5/25)] in the low-load group ( χ2 = 11.90, 19.71, P = 0.001, P < 0.001). Alanine aminotransferase and aspartate aminotransferase levels in the high-load group were (156.24 ± 13.21) U/L and (171.69 ± 13.49) U/L, respectively, which were significantly higher than (125.89 ± 10.54) U/L and (143.26 ± 10.29) U/L in the medium-load group and (89.64 ± 6.75) U/L and (64.89 ± 5.74) U/L] in the low-load group (all P < 0.001). There was no significant difference in the peak load of EBV-DNA between children of different ages and between children of different sexes (both P > 0.05). Conclusion:Children with infectious mononucleosis caused by EPV have a high EBV-DNA peak load. A higher peak load of EVB-DNA indicates a higher risk of liver function damage. More attention should be paid in clinical practice. Effective diagnosis and treatment should be performed in time to control the patient's condition as early as possible.

Predictive indicators of a prolonged course of fever in children with infectious mononucleosis / 中国基层医药

Objective:To explore the relevant predictive indicators of fever course > 7 days in children with infectious mononucleosis.Methods:The clinical data of 163 children with infectious mononucleosis who received treatment in Xi'an Children's Hospital from January 2018 to October 2020 were retrospectively analyzed. According to the heat duration, the children were divided into the fever course > 7 days group ( n = 55) and the fever course ≤ 7 days group ( n = 108). The clinical manifestations and laboratory indexes on admission were compared between the two groups. A logistic regression model was used to analyze the influential factors of fever course in children. A receiver operating curve was used to evaluate the predictive value of heat course > 7 days for infectious mononucleosis. Results:The majority of children with infectious mononucleosis had a heat course of 7 days (21.5%). There were no significant differences in clinical manifestations between the fever course > 7 days group and the fever course ≤ 7 days group (all P > 0.05). Neutrophil count, the proportion of monocytes, aspartate aminotransferase, and the proportion of suppressor T (Ts) cells in the fever course > 7 days group were (15.97 ± 7.60) × 10 9/L, 7.75 (4.93, 10.75)%, 53.00 (22.00, 91.50) U/L, 70.00 (57.00, 75.00)%, respectively, which were significantly higher than (15.21 ± 5.29) × 10 9/L, 5.40 (3.40, 9.60)%, 40.00 (30.00, 63.75) U/L, 63.50 (55.00,70.75)% in the fever course ≤ 7 days group ( t = -5.10, Z = -2.31, Z = -2.26, Z = -2.12, all P < 0.05). The proportion of helper T (Th) cells and the ratio of Th/Ts cells in the fever course > 7 days group were 13.00 (9.00, 17.00)% and 0.19 (0.12, 0.30)%, respectively, which were significantly lower than 16.00 (12.25, 20.75)%, 0.26 (0.18, 0.37)% in the fever course ≤ 7 days group ( Z = 2.44, 2.48, both P < 0.05). Multivariate logistic regression analysis showed that the increased proportion of Ts cells ( OR = 0.96, 95% CI 0.922-0.978, P < 0.05) was an influential factor of the prolonged course of fever. The area under the receiver operating characteristic curve of the proportion of Ts cells was 0.637. The cut-off value, sensitivity, and specificity were 67.50%, 61.3%, and 64.3%, respectively. Conclusion:Children with infectious mononucleosis with a longer heat course have more severe immune responses. The proportion of Ts cells > 67.5% can be used as a risk factor for the fever course > 7 days in children with infectious mononucleosis.

Reassessment of Evidence about Coinfection of Chickenpox and Monkeypox (Mpox) in African Children.

In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the investigators observed a sizable number of coinfections of chickenpox (varicella) and monkeypox. Based on a review of the literature, we propose that chickenpox (human herpesvirus-3 infection) is a risk factor for acquisition of monkeypox infection. Our hypothesis states that the chickenpox skin lesion provides an entry site for the monkeypox virus, which is harbored on a fomite in the environment of the patient. The fact that monkeypox can enter via a scratch or abrasion is a known mechanism of spread for three other poxviruses, including mousepox (ectromelia), orf and molluscum contagiosum. There are many similarities in pathogenesis between certain poxviruses and chickenpox, including a viremia with a cellular stress response leading to high levels of the IL-6 cytokine. One very revealing observation in the two epidemiology studies was that the number of pox as well as the severity of disease in children with chickenpox and monkeypox coinfection was not greater than found in children with monkeypox alone. Based on the above observations, we conclude that, when chickenpox precedes monkeypox, priming of the immune system by the earlier chickenpox infection moderates the severity of the secondary infection with monkeypox. This conclusion also has important public health implications about chickenpox surveillance.