The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection-A Condition Affecting Immunocompromised Patients.

Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7-usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments-such as ribavirin-should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.

The trends of acute hepatitis A and hepatitis E during the COVID-19 pandemic in Japan

Introduction: The prevalence of various infectious diseases has been changing since the COVID-19 pandemic in Japan. Hepatitis A (HA) is transmitted from food and drink contaminated with the hepatitis A virus, while hepatitis E (HE) is a known zoonotic disease. The trends of HA and HE infection during the COVID-19 pandemic are unknown in Japan. Objective(s): In this study, we investigated the incidence of HA and HE before and after the COVID-19 epidemic, and compared the differences in trends between our hospital and Japanese statistics. Method(s): We investigated the number of IgA-HEV and IgM-HAV antibodies tested and positive at our hospital between January 2015 and December 2021. We verified the patient background, blood test findings and outcome of each antibody-positive. Result(s): The number of HE diagnoses /tests (rate) was 2 /187 (1.1%) in 2015, 2 /155 (1.3%) in 2016, 7 /236 (3.0%) in 2017, 11 /234 (4.7%) in 2018 and 15/ 307 (4.9%) in 2019, which was an increasing trend, but the number of tests remained the same but the number of diagnoses decreased 6 /314 (1.9%) in 2020, 2 /296 (1.0%) in 2021. According to Japanese statistics, the number of HE diagnoses showed a gradual increase from 213 in 2015 to 490 in 2019, but a slight decrease was reported in 441 in 2020 and 447 cases in 2021, respectively. On the other hand, there was no marked change in the number of HA diagnoses/tests between 2015 and 2019. 7 cases of HIV co-infection and an epidemic among Men who have Sex with Men (MSM) were observed in 2018. The number of cases decreased markedly to 0 /362 (0%) in 2020 and 0 /339 (0%) in 2021. In Japan, the number of HA diagnoses was in the 200 s from 2015 to 2017, while 925 cases were diagnosed in 2018 and 425 cases in 2019, indicating an epidemic, but the number of HA diagnoses has decreased significantly to 118 in 2020 and 69 in 2021. Conclusion(s): The number of cases of HE, a zoonosis, was reported to have decreased slightly nationwide, even with the coronary disaster, but the number of cases decreased markedly at our facility in Tokyo, suggesting the influence of changes in the lifestyle and activity patterns of the patient population. On the other hand, the number of cases of HA, which had been prevalent in recent years as a result of sexual contact among MSM, has decreased, probably due to a decrease in the influx of cases from overseas as a result of travel restrictions.

Syphilis: "The Great Imitator" Presenting as Acute Hepatitis

Introduction: Syphilis is a multi-systemic disease caused by spirochete Treponema pallidum. Very rarely, it can affect the liver and cause hepatitis. Since most cases of hepatitis are caused by viral illnesses, syphilitic hepatitis can be missed. Here, we present a case of syphilitic hepatitis in a 35-year-old male. Case Description/Methods: Patient was a 35-year-old male who presented to the hospital for jaundice and mild intermittent right upper quadrant abdominal pain. His medical history was only significant for alcohol abuse. His last drink was 4 weeks ago. He was sexually active with men. On exam, hepatomegaly, mild tenderness in the right upper quadrant, jaundice, and fine macular rash on both hands and feet were noted. Lab tests revealed an ALT of 965 U/L, AST of 404 U/L, ALP of 1056 U/L, total bilirubin of 9.5 mg/dL, direct bilirubin of 6.5 mg/dL, INR of 0.96, and albumin of 2.0 g/dL. Right upper quadrant ultrasound showed an enlarged liver but was negative for gallstones and hepatic vein thrombosis. MRI of the abdomen showed periportal edema consistent with hepatitis without any gallstones, masses, or common bile duct dilation. HIV viral load and Hepatitis C viral RNA were undetectable. Hepatitis A & B serologies were indicative of prior immunization. Hepatitis E serology and SARS-CoV-2 PCR were negative. Ferritin level was 177 ng/mL. Alpha-1-antitrypsin levels and ceruloplasmin levels were normal. Anti-Smooth muscle antibody titers were slightly elevated at 1:80 (Normal < 1:20). Anti-Mitochondrial antibody levels were also slightly elevated at 47.9 units (Normal < 25 units). RPR titer was 1:32 and fluorescent treponemal antibody test was reactive which confirmed the diagnosis of syphilis. Liver biopsy was then performed which showed presence of mixed inflammatory cells without any granulomas which is consistent with other cases of syphilitic hepatitis. Immunohistochemical stain was negative for treponemes. Patient was treated with penicillin and did have Jarisch-Herxheimer reaction. ALT, AST, ALP, and total bilirubin down trended after treatment. Repeat tests drawn exactly 1 month post treatment showed normal levels of ALT, AST, ALP, and total bilirubin (Figure). Discussion(s): Liver damage can occur in syphilis and can easily be missed because of the non-specific nature of presenting symptoms. In our patient, the fine macular rash on both hands and feet along with history of sexual activity with men prompted us to test for syphilis which ultimately led to diagnosis and treatment in a timely manner. (Figure Presented).

Outbreaks of different viral etiologies amidst COVID-19 pandemic

The COVID-19 pandemic has severely affected public health system and surveillance of other communicable diseases across the globe. The lockdown, travel constraints and COVID phobia turned down the number of people with illness visiting to the clinics or hospitals. Besides this, the heavy workload of SARS-CoV-2 diagnosis has led to the reduction in differential diagnosis of other diseases. Consequently, it added to the underlying burden of many diseases which remained under-diagnosed. Amidst the pandemic, the rise of emerging and re-emerging infectious diseases was observed worldwide and reported to the World Health Organization i.e., Crimean Congo Hemorrhagic Fever (2022, Iraq;2021 India), Nipah virus (2021, India), Zika virus (2021, India), and H5N1 influenza (2021, India), Monkeypox (2022, multicountry outbreak), Ebola virus disease (2022, DRC, Uganda;2021, DRC, Guinea;2020, DRC), Marburg (2022, Ghana;2021, Guinea), Yellow fever (2022, Uganda, Kenya, West and Central Africa;2021, Ghana, Venezuela, Nigeria;2020, Senegal, Guinea, Nigeria, Gabon;2020, Ethiopia, Sudan, Uganda), Dengue (2022, Nepal, Pakistan, Sao Tome, Temor-Leste;2021, Pakistan), Middle east respiratory syndrome coronavirus (2022, Oman, Qatar;2021, Saudi Arabia, UAE;2020, Saudi Arabia, UAE), Rift valley fever (2021, Kenya;2020, Mauritania), wild poliovirus type 1 (2022, Mozambique), Lassa fever (2022, Guinea, Togo, Nigeria;2020, Nigeria), Avian Influenza (H3N8) (2022, China), Avian Influenza (H5N1) (2022, USA), H10N3 influenza (2021, China), Hepatitis E virus (2022, Sudan), Measles (2022, Malawi, Afghanistan;2020, Burundi, Mexico), Mayaro virus disease (2020, French Guiana), Oropouche virus disease (2020, French Guiana). All these diseases were associated with high morbidity and burdened the public health system during the COVID-19 pandemic. During this critical public health menace, majority of the laboratory workforce was mobilized to the SARS-CoV-2 diagnosis. This has limited the surveillance efforts that likely led to under diagnosis and under-detection of many infectious pathogens. Lockdowns and travel limitations also put a hold on human and animal surveillance studies to assess the prevalence of these zoonotic viruses. In addition, lack of supplies and laboratory personnel and an overburdened workforce negatively impacted differential diagnosis of the diseases. This is especially critical given the common symptoms between COVID-19 and other pathogens causing respiratory illnesses. Additionally, the vaccination programs against various vaccine preventable diseases were also hampered which might have added to the disease burden. Despite these challenges, the world is better prepared to detect and respond to emerging/re-emerging pathogens. India now has more than 3000 COVID-19 diagnostic laboratories and an enhanced hospital infrastructure. In addition, mobile BSL-3 facilities are being validated for onsite sampling and testing in remote areas during outbreak situations and surveillance activities. This will undoubtedly be valuable as the COVID-19 pandemic evolves as well as during future outbreaks and epidemics. In conclusion, an increase in the emergence and re-emergence of viruses demonstrates that other infectious diseases have been neglected during the COVID-19 pandemic. Lessons learned from the infrastructure strengthening, collaborations with multiple stakeholders, increased laboratory and manufacturing capacity, large-scale COVID-19 surveillance, extensive network for laboratory diagnosis, and intervention strategies can be implemented to provide quick, concerted responses against the future threats associated with other zoonotic pathogens.

Viral Hepatitis and Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is characterized by acute decompensation, organ failure, and high short-term mortality. Hepatitis A and hepatitis E are major causes of ACLF. Hepatitis B may also cause ACLF through a flare of hepatitis B, acute infection, or reactivation. Besides supportive care, nucleoside/nucleotide analog therapy should also be initiated in this setting. Nonhepatotropic viruses may rarely also cause ACLF with the severe acute respiratory syndrome coronavirus 2 virus recently being identified with poorer outcomes in those with underlying CLD.

Severe Acute Hepatitis in Children

Viral infections affecting the liver had a serious impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. The discovery of the viral agents of severe acute hepatitis in children triggered interest of the scientific community to establish the pathogenesis and diagnostic techniques to identify the affected population. But, WHO, together with scientists in various affected countries, are working to understand the cause of this infection that does not appear to belong to any of the known five types of hepatitis viruses: A, B, C, D and E. Many cases of severe acute hepatitis of unknown origin in children <10 years of age were reported by the International Health Regulations (IHR) was mainly by adenovirus infection, HAdV-41. Although most acute infections cause mild disease and even go undetected, some can lead to complications and turn fatal. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens for severe acute hepatitis of unknown origin in children.Copyright © 2022, Global Research Online. All rights reserved.

Low Prevalence of HEV Infection and No Associated Risk of HEV Transmission from Mother to Child among Pregnant Women in Vietnam.

Infections with HEV in low- and middle-income countries (LMICs) are associated with increased rates of preterm birth, miscarriage, and stillbirth. The aim of the present study was to investigate HEV infections in pregnant women and the possibility of mother-to-child transmission, and associated outcomes. A total of 183 pregnant women in their third trimester were recruited and followed until delivery. Anti-HEV IgG and IgM were determined via enzyme-linked immunosorbent assay (ELISA), and HEV nucleic acids were detected in stool and cord blood samples. HEV genotypes were identified by Sanger sequencing, and phylogenetic analyses were performed. Mother-to-child transmission and associated adverse outcomes were not observed. Only 2% of patients (n = 4/183) tested positive for anti-HEV IgM, and 8% (n = 14/183) tested positive for anti-HEV IgG antibodies. Cord blood (n = 150) analysis showed that there was no IgM detected, while 4% (n = 6/150) tested positive for anti-HEV IgG, which was consistent with mothers testing positive for anti-HEV IgG. Nucleic acid tests for HEV RNA yielded 2% (n = 4/183) from the serum and stool of pregnant women, and none from cord blood. The HEV isolates belonged to the genotype HEV-3a, with 99% homology with humans and 96% with pigs. No association was found between the risk of HEV infection and pregnancy outcomes or HEV transmission from mother to child. HEV-3 infections of zoonotic origin in pregnancy might have eventually resolved without complications.

CdSe-Co3O4@TiO2 nanoflower-based photoelectrochemical platform probing visible light-driven virus detection.

The design and construction of a visible light-driven photoelectrochemical (PEC) device is described based on a CdSe-Co3O4@TiO2 nanoflower (NF). Moreover, an application to the ultrasensitive detection of viruses, such as hepatitis E virus (HEV), HEV-like particles (HEV-LPs), and SARS-CoV-2 spike protein in complicated lysate solution, is demonstrated. The photocurrent response output of a PEC device based on CdSe-Co3O4@TiO2 is enhanced compared with the individual components, TiO2 and CdSe-Co3O4. This can be attributed to the CdSe quantum dot (QD) sensitization effect and strong visible light absorption to improve overall system stability. A robust oxygen-evolving catalyst (Co3O4) coupled at the hole-trapping site (CdSe) extends the interfacial carrier lifetime, and the energy conversion efficiency was improved. The effective hybridization between the antibody and virus resulted in a linear relationship between the change in photocurrent density and the HEV-LP concentration ranging from 10 fg mL-1 to 10 ng mL-1, with a detection limit of 3.5 fg mL-1. This CdSe-Co3O4@TiO2-based PEC device achieved considerable sensitivity, good specificity, and acceptable stability and demonstrated a significant ability to develop an upgraded device with affordable and portable biosensing capabilities.

P22-10 Prevalence and outcome of Covid-19 in patients with substance abuse disorder presented to tertiary care hospital emergency department

Background: Currently, there is few studies looking at of the risks and outcomes for COVID-19 infection in individuals with substance abuse disorder (SUD). SUD are believed to be at increased risk of covid infection and at more risk of bad outcome. Objective(s): The aim of this study is to describe the prevalence of covid-19 and outcomes in patients with SUD presented to Sultan Qaboos University Hospital Emergency Department (ED) over 1 year. Method(s): It is a retrospective study that included all patients presented to Sultan Qaboos University Hospital Emergency Department from March 20120 to March 2021 who had drug abuse screening done. Patients were included if they are they are found to be positive for SUD and had a covid-19 swab test as well. Result(s): A total of 422 patients were found but only 104 patients met the inclusion criteria 0.99% (103/104) were male and Omani. The age range was 21-62 years old. Covid was positive in 8.6% (9/104). 0.98.5% presented with respiratory symptoms. 15.3% (16/104) had history infective endocarditis and 38.4% (40/104) had psychiatric disease. 57.6% (60/104) are smoker. 67.3 (70/104) were morphine abuser while 25% (26/104) methamphetamine abusers. 72.1% (75/104) were admitted to hospital with 77.8% admission (7/9) in patients with SUD with covid infection. Mortality was 6.7% (7/104) in general, with 33.3% mortality (3/9) in covid positive SUD. 55.6% (5/9) had hepatitis B, C and E compare to 43%(95/104) of covid negative. Further analysis showed, SUD patients with hepatitis B or hepatitis E have 5.5 increased risk of getting infected with covid-19. SUD patients with covid-19 have 11.4 increased risk of death. Drug abusers who are more?> = 30 years old have 4.2 increased risk of getting at least 2 complications (acute kidney injury, rhabdomylosis, aspiration pneumonia liver cirrhosis, ect). Conclusion(s): The prevalence of covid-19 in patients with substance abuse disorder was slightly high, and patients with hepatitis having 5.5 increased risk of getting infected with covid. Covid infection in SUD patients have high morbidity and mortality. Further studies are required to determine factors that would predict a worse prognosis of covid infection in SUD patients. Copyright © 2022 Elsevier B.V.

Integrative Multiomics and Regulatory Network Analyses Uncovers the Role of OAS3, TRAFD1, miR-222-3p, and miR-125b-5p in Hepatitis E Virus Infection.

The hepatitis E virus (HEV) is a long-ignored virus that has spread globally with time. It ranked 6th among the top risk-ranking viruses with high zoonotic spillover potential; thus, considering its viral threats is a pressing priority. The molecular pathophysiology of HEV infection or the underlying cause is limited. Therefore, we incorporated an unbiased, systematic methodology to get insights into the biological heterogeneity associated with the HEV. Our study fetched 93 and 2016 differentially expressed genes (DEGs) from chronic HEV (CHEV) infection in kidney-transplant patients, followed by hub module selection from a weighted gene co-expression network (WGCN). Most of the hub genes identified in this study were associated with interferon (IFN) signaling pathways. Amongst the genes induced by IFNs, the 2'-5'-oligoadenylate synthase 3 (OAS3) protein was upregulated. Protein-protein interaction (PPI) modular, functional enrichment, and feed-forward loop (FFL) analyses led to the identification of two key miRNAs, i.e., miR-222-3p and miR-125b-5p, which showed a strong association with the OAS3 gene and TRAF-type zinc finger domain containing 1 (TRAFD1) transcription factor (TF) based on essential centrality measures. Further experimental studies are required to substantiate the significance of these FFL-associated genes and miRNAs with their respective functions in CHEV. To our knowledge, it is the first time that miR-222-3p has been described as a reference miRNA for use in CHEV sample analyses. In conclusion, our study has enlightened a few budding targets of HEV, which might help us understand the cellular and molecular pathways dysregulated in HEV through various factors. Thus, providing a novel insight into its pathophysiology and progression dynamics.

High-Yield Production of Chimeric Hepatitis E Virus-Like Particles Bearing the M2e Influenza Epitope and Receptor Binding Domain of SARS-CoV-2 in Plants Using Viral Vectors.

Capsid protein of Hepatitis E virus (HEV) is capable of self-assembly into virus-like particles (VLPs) when expressed in Nicotiana benthamiana plants. Such VLPs could be used as carriers of antigens for vaccine development. In this study, we obtained VLPs based on truncated coat protein of HEV bearing the M2e peptide of Influenza A virus or receptor-binding domain of SARS-CoV-2 spike glycoprotein (RBD). We optimized the immunogenic epitopes' presentation by inserting them into the protruding domain of HEV ORF2 at position Tyr485. The fusion proteins were expressed in Nicotiana benthamiana plants using self-replicating potato virus X (PVX)-based vector. The fusion protein HEV/M2, targeted to the cytosol, was expressed at the level of about 300-400 µg per gram of fresh leaf tissue and appeared to be soluble. The fusion protein was purified using metal affinity chromatography under native conditions with the final yield about 200 µg per gram of fresh leaf tissue. The fusion protein HEV/RBD, targeted to the endoplasmic reticulum, was expressed at about 80-100 µg per gram of fresh leaf tissue; the yield after purification was up to 20 µg per gram of fresh leaf tissue. The recombinant proteins HEV/M2 and HEV/RBD formed nanosized virus-like particles that could be recognized by antibodies against inserted epitopes. The ELISA assay showed that antibodies of COVID-19 patients can bind plant-produced HEV/RBD virus-like particles. This study shows that HEV capsid protein is a promising carrier for presentation of foreign antigen.

Expression and Immunogenicity of SARS-CoV-2 Virus-Like Particles based on Recombinant Truncated HEV-3 ORF2 Capsid Protein.

COVID-19 is an emerging disease that poses a severe threat to global public health. As such, there is an urgent demand for vaccines against SARS-CoV-2, the virus that causes COVID-19. Here, we describe a virus-like nanoparticle candidate vaccine against SARS-CoV-2 produced by an E. coli expression system. The fusion protein of a truncated ORF2-encoded protein of aa 439~608 (p170) from hepatitis E virus CCJD-517 and the receptor-binding domain of the spike protein from SARS-CoV-2 were expressed, purified and characterized. The antigenicity and immunogenicity of p170-RBD were evaluated in vitro and in Kunming mice. Our investigation revealed that p170-RBD self-assembled into approximately 24 nm virus-like particles, which could bind to serum from vaccinated people (p < 0.001) and receptors on cells. Immunization with p170-RBD induced the titer of IgG antibody vaccine increased from 14 days post-immunization and was significantly enhanced after a booster immunization at 28 dpi, ultimately reaching a peak level on 42 dpi with a titer of 4.97 log10. Pseudovirus neutralization tests showed that the candidate vaccine induced a strong neutralizing antibody response in mice. In this research, we demonstrated that p170-RBD possesses strong antigenicity and immunogenicity and could be a potential candidate for use in future SARS-CoV-2 vaccine development.

Update on the ongoing investigation into hepatitis in children

Public Health Scotland (PHS) released an update on the ongoing investigation into cases of sudden onset hepatitis (liver inflammation) in children aged ten years or younger on June 10, 2022. Since the previous update on May 27, 2022, one additional case had been discovered, bringing the total number of cases reported in Scotland since the disease first appeared in January 2022 to 32. The UK has now recorded 240 incidents overall, with all affected children seeking medical attention between January and June 7, 2022. The most recent technical briefing, released on May 19, 2022, notes that research is more and more likely to point to the adenovirus as one of the main reasons why childhood hepatitis rates are greater than usual. The most frequent symptoms that the affected youngsters encounter are jaundice and vomiting. Parents should call their GP or another healthcare provider if their kid displays symptoms of jaundice, which include a yellow tinge in the skin or the whites of the eyes. Dark urine, pale gray poop, itchy skin, joint and muscle problems, fatigue, feeling unwell, a high temperature, loss of appetite, and stomach pain are some more symptoms that might occur. Hepatitis A through E, the common viruses that cause infectious hepatitis, have not been found, and there is no proof that the COVID-19 vaccine is connected in any way. Children under five years old, who are too young to have received the vaccine, account for the bulk of cases. According to PHS, there is now little possibility that youngsters will get severe hepatitis. In order to stop the spread of common diseases, parents and other adults are urged to make sure kids practice excellent hand and respiratory cleanliness.

Serological Screening for Middle East Respiratory Syndrome Coronavirus and Hepatitis E Virus in Camels in Kazakhstan.

After the recent Middle East Respiratory Syndrome coronavirus (MERS-CoV) pandemic in 2013, more attention has been paid to the camel as an important source of zoonotic viral infections. Almost simultaneously, in 2013, new genotypes 7 and 8 of the hepatitis E virus (HEV) were discovered in dromedary and Bactrian camels, respectively. HEV 7 was further shown to be associated with chronic viral hepatitis in a transplant recipient. In this study, serological screening for antibodies to MERS-CoV and hepatitis E virus was carried out on large camel farms in the south and west of Kazakhstan. 6.42% of the tested camels were found to be positive for antibodies to the hepatitis E virus, which indicates its circulation in local camel population. For the first time, antibodies to the hepatitis E virus were found in Bactrians, which have been little studied to date. Antibodies to MERS-CoV were not found in the camel sera.

Investigation of coronavirus and hepatitis E virus in rodents in Dali City, Yunnan Province

An investigation of coronavirus (CoV) and hepatitis E virus (HEV) in rodents was performed to understand CoV and HEV infection of rodents in Dali City, Yunnan Province. Rodent samples were obtained in the four towns of Dali city through traps from August 2020 to August 2021. A total of 76 rodents belonging to six species and five genera were captured: Rattus tanezumi, Rattus norvegicus, Apodemus chevrieri, Eothenomys miletus, Niviventer fulvescens, and Mus Pahari. Detection of CoV and HEV was performed by nested-PCR. The infection rate of CoV was 40.74% (11/27) and 2.38% (1/42) in R. norvegicus and R. tanezumi, respectively. The infection rate of HEV was 14.81% (4/27) and 2.38% (1/42) in R. norvegicus and R. tanezumi, respectively. Co-infection with CoV and HEV was detected in two R. norvegicus, with a co-infection rate of 7.41% (2/27). A Basic Local Alignment Search Tool (BLAST) search was performed on partial RNA-dependent RNA polymerase (RdRp) sequences of CoV and HEV. Eleven strains from R. norvegicus were a-CoV, and matched best to strain KY370050 from Rattus losea (Fujian, China), with 99.73% to 99.74% nucleotide (nt) sequency identity. One strain was ss-CoV from R. tanezumi, which displayed 98.21% nt sequence identity with strain MT820632 from Bandicota indica (Yunnan, China). Five strains from R. norvegicus were all HEV-C, and showed 95.87% to 96.21% sequence similarity to strain MN450853 from a patient in Hong Kong, China. In conclusion, CoV and HEV infections are present in rodents in Dali City. Because the host animals of the two viruses are closely related to humans, surveillance and investigations of related viruses should be strengthened.

Plant-Derived Recombinant Vaccines against Zoonotic Viruses.

Emerging and re-emerging zoonotic diseases cause serious illness with billions of cases, and millions of deaths. The most effective way to restrict the spread of zoonotic viruses among humans and animals and prevent disease is vaccination. Recombinant proteins produced in plants offer an alternative approach for the development of safe, effective, inexpensive candidate vaccines. Current strategies are focused on the production of highly immunogenic structural proteins, which mimic the organizations of the native virion but lack the viral genetic material. These include chimeric viral peptides, subunit virus proteins, and virus-like particles (VLPs). The latter, with their ability to self-assemble and thus resemble the form of virus particles, are gaining traction among plant-based candidate vaccines against many infectious diseases. In this review, we summarized the main zoonotic diseases and followed the progress in using plant expression systems for the production of recombinant proteins and VLPs used in the development of plant-based vaccines against zoonotic viruses.

Advances in acute severe hepatitis of unknown etiology in children

Since the International Health Regulations National Focal Point for the United Kingdom alerted the WHO of ten cases of acute severe hepatitis of unknown etiology in children on April 5, 2022, relevant cases have been reported worldwide. These patients had acute hepatitis (negative for hepatitis viruses A-E) and elevated aminotransferase (AST) or alanine aminase (ALT) exceeding 500 U/L. Furthermore, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or adenovirus type F41 have been detected in some cases. This unknown hepatitis has been hypothesized to be induced by a viral reservoir of novel coronavirus superantigen, which repeatedly stimulates the intestines and leads to a multisystem inflammatory syndrome in children (MIS-C), which causes immune abnormalities in the presence of human adenovirus. Although this hypothesis has not been confirmed by any in vivo experimental or clinical studies, it may provide ideas for possible intervention strategies.

Hepatitis E Virus Seroprevalence and Associated Risk Factors in Pregnant Women Attending Antenatal Consultations in Senegal.

In West Africa, research on the hepatitis E virus (HEV) is barely covered, despite the recorded outbreaks. The low level of access to safe water and adequate sanitation is still one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Herein, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A consecutive and non-redundant recruitment of participants was carried out over the period of 5 months, from March to July 2021. A total of 1227 consenting participants attending antenatal clinics responded to a standard questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. The overall HEV seroprevalence was 7.8% (n = 96), with 0.5% (n = 6) and 7.4% (n = 91) for HEV IgM and HEV IgG, respectively. One of the participant samples was IgM/IgG-positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer's instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p < 0.0001), by the regularity of income (p = 0.0043), and by access to sanitation services (p = 0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental, and behavioral aspects for a better management of HEV infection in Senegal.

Comparative analysis of acute on chronic liver failure related to herbs and anti-tubercular drugs

Objectives: Liver injury precipitated by drugs and herbal medicines( DHMs) can have variable presentations and outcomes. In Indian subcontinent, drug induced liver injury due to Anti-tubercular drugs( ATDs) and inadvertent herbs induced liver injury (HILI) are common. Comparative natural history and outcome of acute-onchronic liver failure(ACLF) due to common DHMs is largely unknown. Materials and Methods: Consecutive in-patients with ACLF precipitated by herbs or ATDs(year 2010-2021) were compared for baseline clinical profile, disease severity, histological features and organ failures. Treatment outcomes and predictors of in-hospital mortality were also analyzed. Results: 529 patients presented with ACLF related to HILI(ACLF-H, n = 430) and ATDs(ACLF-D, n = 99) [Mean Age-47.6 - 14 years, mean MELD score and HVPG were 29.1 - 5.4 and 15.5 - 3.4 mmHg respectively]. 61.4% patients had underlying histological cirrhosis. 21.2% patients had additional superadded acute insult [severe alcoholic hepatitis(n = 66), acute hepatitis E or A(n = 24/15)]. Twelve percent ACLF-H patients presented with clinical cholestasis, autoimmune hepatitis(n = 18) and hypersensitivity reactions(n = 4). Most common recognizable agent associated with ACLF-H was Tinospora cordifolia (n = 35,8.1%), inadvertently used in Indian households during the COVID-19 pandemics. Patients with ACLF-H as compared to ACLF-D had higher male preponderance (70.9% vs. 54.5%;p-0.002) and peripheral eosinophilia (6.4% vs. 1%;p-0.03), clinical cholestasis (19.6% vs 10.8%;p-0.05) and acute kidney injury (44.4% vs. 28.3%;p-0.003) at presentation. Use of plasma exchange(18.5%) had no impact on outcomes. None of the patients underwent liver transplantation. In-hospital mortality(19.2%) was higher in ACLF-D compared to HILI ACLF-H (31.3% vs. 17.2%;p-0.002). Presence of AKI [HR:5.5 (95%CI:2.78 to 11.1)], hepatic encephalopathy[HR:4.4(95%CI:1.76 to 11)] and pneumonia[ HR:7.2(95%CI: 3.59 to 14.65)] were independent predictors of mortality. Conclusion: Herbs and anti-tubercular drugs are common precipitants of ACLF in India and have high in-hospital mortality resulting from sepsis and organ(s) failure. In the absence of specific treatment options, prevention and early and careful monitoring of liver functions is of utmost importance.