Viral Causes Research Articles

What are the essential determinants of human papillomavirus carcinogenesis?

Human papillomavirus (HPV) infection is the leading viral cause of cancer. Over the past several decades, research on HPVs has provided remarkable insight into human cell biology and into the pathology of viral and non-viral cancers. The HPV E6 and E7 proteins engage host cellular proteins to establish an environment in infected cells that is conducive to virus replication. They rewire host cell signaling pathways to promote proliferation, inhibit differentiation, and limit cell death. The activity of the "high-risk" HPV E6 and E7 proteins is so potent that their dysregulated expression is sufficient to drive the initiation and maintenance of HPV-associated cancers. Consequently, intensive research efforts have aimed to identify the host cell targets of E6 and E7, in part with the idea that some or all of the virus-host interactions would be essential cancer drivers. These efforts have identified a large number of potential binding partners of each oncoprotein. However, over the same time period, parallel research has revealed that a relatively small number of genetic mutations drive carcinogenesis in most non-viral cancers. We therefore propose that a high-priority goal is to identify which of the many targets of E6 and E7 are critical drivers of HPV carcinogenesis. By identifying the cancer-driving targets of E6 and E7, it should be possible to better understand the distinct roles of other targets, perhaps in the viral life cycle, and to focus efforts to develop anti-cancer therapies on the subset of virus-host interactions for which therapeutic intervention would have the greatest impact.

Unraveling Sepsis Epidemiology in a Low- and Middle-Income Intensive Care Setting Reveals the Alarming Burden of Tropical Infections and Antimicrobial Resistance: A Prospective Observational Study (MARS-India).

Our study addresses the sepsis research gap in lower middle-income countries, notably India. Here, we investigate community-acquired sepsis comprehensively and explore the impact of tropical microbiology on aetiology and outcomes. MARS-India was a prospective observational study from Dec-2018 to Sep-2022 in a tertiary-care hospital in South India. Adult patients within 24hrs of ICU admission meeting the Sepsis 3.0 definition were enrolled, with 6-months follow-up (http://clinicaltrials.gov number NCT03727243). Over 4000 patients were screened on ICU admission, with 1000 unique patients meeting the inclusion criteria. Median age was 55 years (IQR: 44-65) with a male preponderance (66%). Almost half the cohort resided in villages (46.5%) and 74.6% worked in the primary sector. Mortality in-hospital was 24.1%. Overall, ∼54% had confirmed microbiological diagnosis. Over 18% had a viral cause of sepsis. Surprisingly, we identified leptospirosis (10.6%), scrub typhus (4.1%), dengue (3.7%) and Kyasanur forest disease (1.6%) as notables causes of sepsis. All these infections showed seasonal variation around the monsoon. In community-acquired infections we observed substantial resistance to 3rd generation cephalosporins and carbapenems. In India, sepsis disproportionally affects a younger and lower socio-economic demographic, yielding high mortality. Tropical and viral sepsis carry a significant burden. Analyzing local data, we pinpoint priorities for public health and resources, offering valuable insights for global sepsis research.

HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion is attributable to viral causes including hepatitis B (HBV) and C virus (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC. To determine the extent to which the viral status and sex impact the molecular and immune profiles of HCC, we performed differential expression and immune cell deconvolution analyses. We identified a large number of differentially expressed genes unique to the HBV or HCV tumor:tumor-adjacent comparison. Pathway enrichment analyses demonstrated that changes unique to the HCV tumor:tumor-adjacent tissue were predominated by changes in immune pathways. Immune cell deconvolution demonstrated that HCV tumor-adjacent tissue had the largest immune cell infiltrate, with no difference in the immune profiles within HBV and HCV tumor samples. Overall, this work demonstrates the convergence of HBV- and HCV-mediated HCC on a similar transcriptomic landscape and immune profile despite differences in the surrounding tissue.

Viral etiologies of acute liver failure.

Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.

Clinical Significance of Biliary Invasion at Diagnosis in Barcelona Clinic Liver Cancer Stage B–C Hepatocellular Carcinoma: A Nationwide Cohort Analysis in South Korea

Introduction: Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B–C (BCLC B–C) HCC. Methods: The Korean Liver Cancer Study Group randomly extracted data of patients with HCC enrolled in the Korean Central Cancer Registry between 2011 and 2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein (AFP) level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4,077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, AFP, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre-propensity score matching cohort to form a matched cohort (propensity score matching cohort). Results: The pre-propensity score matching cohort included 4,077 patients with BCLC B–C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, 1- and 2-year overall survival (OS) rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p < 0.0001). Corresponding cancer-specific survival (CSS) rates at 1 and 2 years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p < 0.0001). Although biliary invasion was a significant factor affecting overall and CSS rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p = 0.153) and cancer-specific (p = 0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p = 0.603) or cancer-specific (p = 0.960) survival rates in the univariate analyses. One- and 2-year OS were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding CSS at one and 2 years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that AFP levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and CSS rates. Conclusion: Biliary invasion at diagnosis in patients with BCLC B–C does not affect overall or CSS rates; however, other prognostic factors associated with biliary invasion could have a greater impact.

AN ACUTE GASTROENTERITIS OUTBREAK IN A KINDERGARTEN

Objective: To detect the etiological cause of an acute gastroenteritis outbreak at St. Anna kindergarten in the village of Resilovo, region Kyustendil. Materials and Methods: A total of 22 faecal specimens from children (n = 18) and staff (n = 4) were tested. Multiplex RT-PCR with specific primer pairs detecting the most common viral causes of gastroenteritis (noroviruses, rotaviruses, sapoviruses, intestinal adenoviruses and intestinal astroviruses) was applied to detect the viral causative agent. Noroviruses were detected and sequenced and subsequent phylogenetic analysis was carried out. Results: Genogroup II noroviruses were detected in five samples from children and one sample from staff (6/22) or in 27.3% of the specimens. According to WHO criteria, this proves that noroviruses have caused the epidemic outbreak. Detected noroviruses were subjected to sequencing and subsequent phylogenetic analysis, with data identifying genotype 17 (GII.17) as the causative agent. Conclusion: Norovirus genotype 17 (GII.17) was first detected in Bulgaria in 2015 as the causative agent of an outbreak in a secondary school in the town of Pravets. In 2016, the circulation of this genotype was again established in sporadic cases, and in 2022 it was found to be the cause of the epidemic gastroenteritis outbreak in a kindergarten in the village of Resilovo. To protect public health, continuous monitoring and targeted search for viral intestinal agents is essential, regardless of the transient and usually mild course of the disease.

A Decade of Chronic Norovirus Infection Surveillance at the NIH Clinical Research Center: Clinical Characteristics, Molecular Epidemiology, and Replication.

Noroviruses are an important viral cause of chronic diarrhea in immunocompromised individuals. We collected norovirus-positive stool samples (n=448) from immunocompromised patients (n=88) at the National Institutes of Health Clinical Research Center, U.S. from 2010-2022. We assessed clinical characteristics of the cohort, norovirus molecular epidemiology, and infectivity of norovirus specimens in human intestinal enteroids (HIEs) monolayers. Thirty-nine of the 88 patients had sequential stool samples that allowed documentation of chronic norovirus infection with shedding levels ranging from 104 to 1011 genome copies/g of stool. The majority with confirmed chronic norovirus infection in this cohort (32/39, 82%) had clinical evidence of an inborn error of immunity (13 identified monogenic diseases), most with combined immunodeficiency (15 of 32) or common variable immunodeficiency (11 of 32). Noroviruses detected in the cohort were genetically diverse: both Genogroup I (GI.2, GI.3, GI.5, and GI.6) and Genogroup II (GII.1-GII.4, GII.6, GII.7, GII.12, GII.14, and GII.17) genotypes were detected, with GII.4 variants (Osaka, Apeldoorn, Den Haag, New Orleans, and Sydney) predominant (51 of 88, 57.9%). Viruses belonging to the GII.4 Sydney variant group that replicated in HIEs (n=9) showed a higher fold-increase in RNA genome copies during infection compared to others that replicated. Genetically and biologically diverse noroviruses established chronic infection in individuals with both inborn and acquired immunologic defects enrolled in an NIH surveillance study spanning 12 years, demonstrating the unique nature of each virus and host interaction.

Looking Back, Moving Forward: Challenges and Opportunities for Global Cervical Cancer Prevention and Control.

Despite the introduction of Pap testing for screening to prevent cervical cancer in the mid-20th century, cervical cancer remains a common cause of cancer-related mortality and morbidity globally. This is primarily due to differences in access to screening and care between low-income and high-income resource settings, resulting in cervical cancer being one of the cancers with the greatest health disparity. The discovery of human papillomavirus (HPV) as the near-obligate viral cause of cervical cancer can revolutionize how it can be prevented: HPV vaccination against infection for prophylaxis and HPV testing-based screening for the detection and treatment of cervical pre-cancers for interception. As a result of this progress, the World Health Organization has championed the elimination of cervical cancer as a global health problem. However, unless research, investments, and actions are taken to ensure equitable global access to these highly effective preventive interventions, there is a real threat to exacerbating the current health inequities in cervical cancer. In this review, the progress to date and the challenges and opportunities for fulfilling the potential of HPV-targeted prevention for global cervical cancer control are discussed.

Knowledge, and attitude of medical students about role of human papilloma virus, and vaccine in head and neck cancer

BackgroundPapilloma DNA virus which is most common sexually transmitted disease to both sexes. The infection either benign or malignant affecting head and neck region. Aim of the studyAssess the level of knowledge, and attitude, of medical students about Human Papilloma virus, vaccine, and its role in head and neck cancer development. Materials and methodsA descriptive cross-sectional survey was conducted on 357 undergraduate medical students. Data were collected by online Google form researcher made questionnaires which was analyzed using SPSS 25. ResultsThere are 357 medical undergraduate students from different educational stages participated in this study. This study was shown 176 (49.3 %) of medical students agreed that smoking Tobacco are the most common causes for development oral cancer followed by viruses 98 (27.5 %), that 57.4 % of medical students reported that HPV was the main viral cause. As for the questions concerning HPV mode of transmission, almost (85.7 %) stated sexual transmission, (79.8 %) skin to skin direct contact. Most of the participants (92.2 %) agreed that primary prevention can decrease the risk of infection with HPV, and 43.4 % strongly agreed that vaccination plays an important role in HPV prevention. ConclusionsThere is a requirement within the existing curriculum and syllabus to include more education, seminars, and training courses on HPV, role in HNC, prevention, and vaccination, and mainly for students in the preclinical academic years. Application of a virtual classroom viral module or communicating workshop would likely improve knowledge and attitudes of the students for their future medical tasks.

Assessment of Nurse's Knowledge toward Human Herpes Virus 6 HHV-6 Infection in NICU

Background: The infant contracted Herpes Simplex Virus (HSV) during the process of being born. The worldwide occurrence of NH is approximately 10 cases per 100,000 births, and it is associated with substantial risks of illness and death. Objective: To evaluate nurses' level of understanding regarding HHV-6 infection in the neonatal intensive care unit (NICU) for newborn infants. The study employed a descriptive research design methodology to achieve its objective. A representative sample of 50 nurses currently employed in neonatal critical care units. Tool I: An Arabic-language structured interview questionnaire. The study encompassed many demographic factors of nurses, such as gender, age, educational attainment, years of experience in the Neonatal Intensive Care Unit (NICU), completion of training on HHV-6 infection, and the source of information. The second tool, the knowledge assessment sheet, focused on HHV-6 infection. The findings indicate that the study included exclusively female nurses, comprising 46.0% of the sample, while males accounted for 54%. Furthermore, the educational background of the participants primarily consisted of graduates from nursing institutes and colleges, with each group representing a substantial proportion of 34%. Conclusion: Our findings indicate that we have chosen to dismiss the null hypothesis, which posits that there is no correlation between the demographic attributes of nurses and their degree of understanding regarding herpes virus type 6 infection. Instead, we have opted to embrace the alternative hypothesis. Recommendations: Provide nurses with a thorough knowledge of the viral causes and risk factors linked to HSV type 6 infections in pregnant women.

Ambulatory antibiotic prescription rates for acute respiratory infection rebound two years after the start of the COVID-19 pandemic.

During the COVID-19 pandemic, acute respiratory infection (ARI) antibiotic prescribing in ambulatory care markedly decreased. It is unclear if antibiotic prescription rates will remain lowered. We used trend analyses of antibiotics prescribed during and after the first wave of COVID-19 to determine whether ARI antibiotic prescribing rates in ambulatory care have remained suppressed compared to pre-COVID-19 levels. Retrospective data was used from patients with ARI or UTI diagnosis code(s) for their encounter from 298 primary care and 66 urgent care practices within four academic health systems in New York, Wisconsin, and Utah between January 2017 and June 2022. The primary measures included antibiotic prescriptions per 100 non-COVID ARI encounters, encounter volume, prescribing trends, and change from expected trend. At baseline, during and after the first wave, the overall ARI antibiotic prescribing rates were 54.7, 38.5, and 54.7 prescriptions per 100 encounters, respectively. ARI antibiotic prescription rates saw a statistically significant decline after COVID-19 onset (step change -15.2, 95% CI: -19.6 to -4.8). During the first wave, encounter volume decreased 29.4% and, after the first wave, remained decreased by 188%. After the first wave, ARI antibiotic prescription rates were no longer significantly suppressed from baseline (step change 0.01, 95% CI: -6.3 to 6.2). There was no significant difference between UTI antibiotic prescription rates at baseline versus the end of the observation period. The decline in ARI antibiotic prescribing observed after the onset of COVID-19 was temporary, not mirrored in UTI antibiotic prescribing, and does not represent a long-term change in clinician prescribing behaviors. During a period of heightened awareness of a viral cause of ARI, a substantial and clinically meaningful decrease in clinician antibiotic prescribing was observed. Future efforts in antibiotic stewardship may benefit from continued study of factors leading to this reduction and rebound in prescribing rates.

Cancer risk in people living with HIV and solid organ transplant recipients: a systematic review and meta-analysis

Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations. We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679. 46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I2=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I2=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I2=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I2=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I2=99·8%; 10·24 [8·48-12·35], I2=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only. Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents. US National Cancer Institute, National Institutes of Health.

Viral pathogens in domestic cats in southern Italy: A retrospective analysis in Sicily, 2020–2022

A retrospective study was carried out on selected feline viral pathogens detected in domestic cat in Sicily, southern Italy. Samples from 64 cats, collected from 2020 to 2022, were analysed for the presence of feline panleukopenia virus, canine parvovirus type 2 (CPV-2), feline coronavirus (FCoV), feline calicivirus (FCV), feline herpesvirus type 1, norovirus (NoV), and rotavirus (RoV). Single (45 %) or mixed (38 %) viral infections were detected. FPV, related with other Italian FPV strains, remains the main viral cause of infection (66 %). CPV-2c Asian lineage strains (3 %) were detected for the first time in domestic cats in Europe. FCoV (29.6 %), either enteric or systemic, and systemic FCV (18.7 %) infections were detected in positive cats. Less commonly reported viruses (GIV.2/GVI.2 NoVs, RoV), potentially related to the animal/human interface, were detected at lower rates as well (5 %). The present epidemiological data suggest the need to improve disease prevention, immunization, and biosecurity strategies.

NSAIDs for early management of acute respiratory infections.

To review the rationale for and the potential clinical benefits of an early approach to viral acute respiratory infections with NSAIDs to switch off the inflammatory cascade before the inflammatory process becomes complicated. It has been shown that in COVID-19 as in other viral respiratory infections proinflammatory cytokines are produced, which are responsible of respiratory and systemic symptoms. There have been concerns that NSAIDs could increase susceptibility to SARS-CoV-2 infection or aggravate COVID-19. However, recent articles reviewing experimental research, observational clinical studies, randomized clinical trials, and meta-analyses conclude that there is no basis to limit the use of NSAIDs, which may instead represent effective self-care measures to control symptoms. The inflammatory response plays a pivotal role in the early phase of acute respiratory tract infections (ARTIs); a correct diagnosis of the cause and a prompt therapeutic approach with NSAIDs may have the potential to control the pathophysiological mechanisms that can complicate the condition, while reducing symptoms to the benefit of the patient. A timely treatment with NSAIDs may limit the inappropriate use of other categories of drugs, such as antibiotics, which are useless when viral cause is confirmed and whose inappropriate use is responsible for the development of resistance.

Infectious etiologies of persistent and chronic diarrhea in Asian developing countries: A systematic review and meta-analysis.

Infectious causes of diarrhea contribute significantly to morbidity in Asia. We conducted a systematic review and meta-analysis of the prevalence of infectious etiologies of persistent and chronic diarrhea in Asian adults. Searches were performed on PubMed and Scopus for studies from January 1, 1970, to May 30, 2023. Sixteen studies were identified and included. The meta-analysis was conducted with the random-effects method, estimating the pooled prevalence of groups of infectious pathogens as causes of persistent and chronic diarrhea among Asian adults. The findings were highly heterogeneous and indicative of publication bias. The majority of studies were conducted on persons living with human immunodeficiency virus infection (PLHIV). The studies were predominantly from low-income and middle-income Asian countries. The most common cause was parasitic, with a pooled prevalence of 0.52 (95% confidence interval 0.28-0.65, I2=99%, Cochran's Q=1027.44, P<0.01), followed by bacterial, fungal, and viral causes, which were substantially rarer. Negative microbiological testing was also common, with a pooled prevalence for a negative test being 0.37 (95% confidence interval 0.17-0.52, I2=99%, Cochran's Q=1027.44, P<0.01). Subgroup analyses of studies conducted among PLHIV, from year 2000 and among those conducted in Southeast Asia showed a similar prevalence of parasitic causes of diarrhea. In conclusion, inAsian adults with persistent and chronic diarrhea, parasitic causes were most prevalent. However, the estimate of true prevalence is limited by significant heterogeneity among the available studies. More study in this field is required, especially examining PLHIV in the post-antiretroviral therapy era and from high-income countries.

Differential associations of fine and coarse particulate air pollution with cause-specific pneumonia mortality: A nationwide, individual-level, case-crossover study

BackgroundThe connections between fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) and daily mortality of viral pneumonia and bacterial pneumonia were unclear. ObjectivesTo distinguish the connections between PM2.5 and PM2.5-10 and daily mortality due to viral pneumonia and bacterial pneumonia. MethodsUsing a comprehensive national death registry encompassing all areas of mainland China, we conducted a case-crossover investigation from 2013 to 2019 at an individual level. Residential daily particle concentrations were evaluated using satellite-based models with a spatial resolution of 1 km. To analyze the data, we employed the conditional logistic regression model in conjunction with polynomial distributed lag models. ResultsWe included 221,507 pneumonia deaths in China. Every interquartile range (IQR) elevation in concentrations of PM2.5 (lag 0–2 d, 37.6 μg/m3) was associated with higher magnitude of mortality for viral pneumonia (3.03%) than bacterial pneumonia (2.14%), whereas the difference was not significant (p-value for difference = 0.38). An IQR increase in concentrations of PM2.5-10 (lag 0–2 d, 28.4 μg/m3) was also linked to higher magnitude of mortality from viral pneumonia (3.06%) compared to bacterial pneumonia (2.31%), whereas the difference was not significant (p-value for difference = 0.52). After controlling for gaseous pollutants, their effects were all stable; however, with mutual adjustment, the associations of PM2.5 remained, and those of PM2.5-10 were no longer statistically significant. Greater magnitude of associations was noted in individuals aged 75 years and above, as well as during the cold season. ConclusionThis nationwide study presents compelling evidence that both PM2.5 and PM2.5-10 exposures could increase pneumonia mortality of viral and bacterial causes, highlighting the more robust effects of PM2.5 and somewhat higher sensitivity of viral pneumonia.

Evaluating Acute Viral Gastroenteritis Severity: Modified Vesikari and Clark Scoring Systems.

Acute gastroenteritis (AGE) is the second leading cause of death in children worldwide. Objectively evaluating disease severity is critical for assessing future interventions. We used data from a large, prospective surveillance study to assess risk factors associated with severe presentation using modified Vesikari score (MVS) and Clark score (CS) of severity. From December 1, 2012 to June 30, 2016, AGE surveillance was performed for children between 15 days and 17 years old in the emergency, inpatient, and outpatient settings at Vanderbilt's Monroe Carell Jr. Children's Hospital in Nashville, TN. Stool specimens were tested for norovirus, sapovirus, rotavirus, and astrovirus. We compared demographic and clinical characteristics, along with the MVS and CS, by viral detection status and by setting. Of the 6309 eligible children, 4216 (67%) were enrolled, with 3256 (77%) providing a stool specimen. The median age was 1.9 years, 52% were male, and 1387 (43%) of the stool samples were virus positive. Younger age, male sex, hospitalization, and rotavirus detection were significantly associated with higher mean MVS and CS. Non-Hispanic Black race and ethnicity was associated with a lower mean MVS and CS as compared with non-Hispanic white race and ethnicity. Prematurity and enrollment in the ED were associated with higher mean CS. The 2 scoring systems were highly correlated. Rotavirus continues to be associated with more severe pediatric illness compared with other viral causes of AGE. MVS and CS systems yielded comparable results and can be useful tools to assess AGE severity.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

Molecular characterization of plasma virome of hepatocellular carcinoma (HCC) patients

Hepatocellular carcinoma (HCC) stands as the most common cancer type, arising from various causes, and responsible for a substantial number of cancer-related fatalities. Recent advancements in viral metagenomics have empowered scientists to delve into the intricate diversity of the virosphere, viral evolution, interactions between viruses and their hosts, and the identification of viral causes behind disease outbreaks, the development of specific symptoms, and their potential role in altering the host’s physiology. The present study had the objective of “Molecular Characterization of HBV, HCV, anelloviruses, CMV, SENV-D, SENV-H, HEV, and HPV viruses among individuals suffering from HCC.” A total of 381 HCC patients contributed 10 cc of blood each for this study. The research encompassed the assessment of tumor markers, followed by molecular characterization of HBV, HCV, Anelloviruses (TTV, TTMV, and TTMDV), SENV-H and SENV-D viruses, HEV, CMV, and HPV, as well as histopathological examinations. The outcomes of this study revealed that majority of the HCC patients 72.4% (276/381) were male as compared to females. HCV infection, at 76.4% (291 out of 381), exhibited a significant association (p < 0.05) with HCC. Most patients displayed singular lesions in the liver, with Child Pugh Score Type B being the predominant finding in 45.2% of cases. Plasma virome analysis indicated the prevalence of TTMDV (75%), followed by TTMV (70%) and TTV (42.1%) among anelloviruses in HCC patients. Similarly, SENV-H (52%) was followed by SENV-D (20%), with co-infections at 15%. The presence of CMV and HEV among the HCC patients was recorded 5% each however 3.5% of the patients showed the presence of HPV. In conclusion, this study underscores that HCC patients serve as reservoirs for various pathogenic and non-pathogenic viruses, potentially contributing to the development, progression, and severity of the disease.

Development of a non-infectious control for viral hemorrhagic fever PCR assays.

Assay validation is an essential component of disease surveillance testing, but can be problematic in settings where access to positive control material is limited and a safety risk for handlers. Here we describe a single non-infectious synthetic control that can help develop and validate the PCR based detection of the viral causes of Crimean-Congo hemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease and Rift Valley fever. We designed non-infectious synthetic DNA oligonucleotide sequences incorporating primer binding sites suitable for five assays, and a T7 promotor site which was used to transcribe the sequence. Transcribed RNA was used as template in a dilution series, extracted and amplified with RT-PCR and RT-qPCR to demonstrate successful recovery and determine limits of detection in a range of laboratory settings. Our results show this approach is adaptable to any diagnostic assay requiring validation of nucleic acid extraction and/or amplification, particularly where sourcing reliable, safe material for positive controls is infeasible.