Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review

BACKGROUND Occult hepatitis B infection(OBI)is a globally prevalent infection,with its frequency being influenced by the prevalence of hepatitis B virus(HBV)infection in a particular geographic region,including Africa.OBI can be transmitted th-rough blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma(HCC).The associated HBV genotype influences the infection.AIM To highlight the genetic diversity and prevalence of OBI in Africa.METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed,Google Scholar,Science Direct,and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa.RESULTS The synthesis included 83 articles,revealing that the prevalence of OBI varied between countries and population groups,with the highest prevalence being 90.9%in patients with hepatitis C virus infection and 38%in blood donors,indicating an increased risk of HBV transmission through blood transfusions.Cases of OBI reactivation have been reported following chemotherapy.Genotype D is the predominant,followed by genotypes A and E.CONCLUSION This review highlights the prevalence of OBI in Africa,which varies across countries and population groups.The study also demonstrates that genotype D is the most prevalent.

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti

BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by 2030.Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti city.METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants.The study ran from January 2021 to May 2022,and infants were followed up to 7 mo of age.HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,Strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth.These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis.Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response.All statistical analyses were performed with version 4.0.1 of the R software.RESULTS Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 years.The MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/mL.Of the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HB<100 mIU/mL)after HBV vaccination and hepatitis B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels(>200000 IU/mL)and hepatitis B e antigen-positive status(odds ratio=158,95%confidence interval:5.05-4958,P<0.01).Birth weight<2500 g was associated with a poor immune response to vaccination(odds ratio=34,95%confidence interval:3.01-383.86,P<0.01).CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target,this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV.Therefore,further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

Humoral Response and Tolerance of Vaccination against SARS-CoV-2 in Adults Senegalese Patients Undergoing Hemodialysis: A Multicenter Prospective Study

Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to assess the immunological response to vaccination in Senegalese hemodialysis patients. Patients and Methods: We conducted a prospective study, in two dialysis centers in Dakar from March 30th to August 30th, 2021 including patients on hemodialysis for >6 months, vaccinated against SARS-CoV-2 according to the vaccination schedule recommended by WHO. A vaccine response was considered positive when seroconversion was observed after one dose of vaccine. The clinical efficacy of immunization was defined as the absence of new COVID-19 infection in patients who received a complete vaccination. Results: Among the 81 patients included in the study, 7.4% had anti-Spike IgM antibodies before their first vaccination. Seroprevalence of IgM antibodies was 38.3% one month after the first vaccine dose (at M1) and 8.6% one month after the second dose (at M4). Anti-Spike IgG antibodies were present in 40.3% of patients before vaccination, in 90.1% at M1, and in 59.7% at M4. Among patients previously infected with SARS-CoV-2, 10.2% had IgM antibodies at M0, 31.6% at M1, and 10.5% at M4 post-vaccination. Similarly, seroprevalences of IgG antibodies in this subgroup were 31.5%, 61.3%, and 50.0% respectively at M0, M1, and M4 post-vaccination. A comparison of seroconversion rates between M0 and M4 showed significant differences only for IgG in COVID-19 naive patients. Mean duration in dialysis and the existence of previous COVID-19 infection were associated with patients’ vaccinal response after the two doses. Age, gender and the use of immunosuppressive treatment did not influence post-vaccinal antibody production. Conclusion: Vaccination against COVID-19 in Senegalese hemodialysis patients induced a low seroconversion rate but it was well tolerated. Moreover, the induced protection was neither strong nor durable, particularly in patients with longer duration in dialysis.

Next-generation sequencing in clinical virology: Discovery of new viruses

Viruses are a cause of significant health problem world-wide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of nextgeneration sequencers(NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequenceindependent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery.

Contribution of Automated Antigen Tests, the LumiraDx Ag Test in the Response during the Second Wave of the COVID-19 Pandemic in Bangui

Context and objective: The COVID-19 pandemic has become a major public health problem and has mobilized many innovative means of diagnosis. The Central African Republic is not spared. The emergence of variants and their impact require health monitoring despite the obligation of vaccination. The purpose of this campaign was to determine the circulation of pending second-wave variants. Patients and Methods: A second mass screening campaign took place from 02 to 22 July 2021 in the main land and river entry points of Bangui (Exit North-PK12, Exit South-PK9, Port Beach) and at the LNBCSP. Antigenic and RT-PCR tests carried out on nasopharyngeal samples made it possible to select strains which were finally sequenced. Results: Of 2687 participants included in the study, 53 (1.97%) were positive for SARS-CoV-2. Thirteen (1.53%) were male and 40 (2.18%) female. The analyses carried out on the LumiraDx analyzer were positive for 109 samples against 53 on the RT-PCR. The prevalence was higher in the most tested age groups (30 to 50 years) with two clusters identified. B.1.617.2 (Delta) variants were predominant (57%). Conclusion: SARS-CoV-2 continues to circulate. The acquisition of automated antigenic tests (LumiraDx&#174) with sensitivity and specificity close to those of the reference test (RT-PCR) will allow better mass diagnosis for an optimization of the surveillance of COVID-19 in our countries with limited resources. The predominance of the B.1.617.2 (Delta) variant would suggest a third wave in the Central African Republic.

番木瓜抗病突变体阻碍环斑病毒体内运转

应用RT PCR一步法检测了PRSVYs株系在感病番木瓜及其抗病突变体植株体内的运转动态 ,结果表明 :在感病植株中 ,接种后 48hr接种叶的未接种部位可检出病毒 ,第 4天部分接种叶柄可检出病毒 ,第 6天植株各部位均能检出病毒 ;而在抗病植株中 ,接种后可以而且仅能在接种部位检出病毒 ;因而认为抗病突变体能够阻碍病毒从接种部位运出及 (或 )

Recent advances in molecular diagnostics of hepatitis Bvirus

Hepatitis B virus(HBV)is one of the important global health problems today.Infection with HBV can lead to a variety of clinical manifestations including severe hepatic complications like liver cirrhosis and hepatocellular carcinoma.Presently,routine HBV screening and diagnosis is primarily based on the immuno-detection of HBV surface antigen(HBsAg).However,identification of HBV DNA positive cases,who do not have detectable HBsAg has greatly encouraged the use of nucleic acid amplification based assays,that are highly sensitive,specific and are to some extent tolerant to sequence variation.In the last few years,the field of HBV molecular diagnostics has evolved rapidly with advancements in the molecular biology tools,such as polymerase chain reaction(PCR)and real-time PCR.Recently,apart of PCR based amplification methods,a number of isothermal amplification assays,such as loop mediated isothermal amplification,transcription mediated amplification,ligase chain reaction,and rolling circle amplification have been utilized for HBV diag-nosis.These assays also offer options for real time detection and integration into biosensing devices.In this manuscript,we review the molecular technologies that are presently available for HBV diagnostics,with special emphasis on isothermal amplification based technologies.We have also included the recent trends in the development of biosensors and use of next generation sequencing technologies for HBV.

Development of a Polyclonal Antibody-based AC-ELISA and Its Comparison with PCR for Diagnosis of Canine Parvovirus Infection

A polyclonal antibody-based antigen-capture ELISA （AC-ELISA） has been developed for detection of Canine parvovirus （CPV） antigens in faecal samples of dogs. The assay uses rabbit anti-CPV polyclonal antibody as the capture antibody, guinea pig anti-CPV polyclonal antibody as tracing antibody and anti-guinea pig HRPO conjugate as the detection system. The optimum dilution of the capture antibody and the tracing antibody capable of detecting the CPV-2 antigens was found to be 1：1 600 and 1：400, respectively, in the check-board titration. In this study, a total of 152 samples （129 faecal samples and 23 cell culture supernatant） were tested both by AC-ELISA and by polymerase chain reaction （PCR）. Of the samples tested, 69 and 78 samples were found positive by AC-ELISA and PCR, respectively. The AC-ELISA had relative sensitivity, relative specificity and accuracy of 88.4%, 100.0% and 91.4% respectively. The analytical sensitivity of AC-ELISA was estimated to be 102.8 TCID50/mL whereas PCR sensitivity was 100.8 TCIDs0/mL. The AC-ELISA is a simple, quick and reliable method for screening large numbers of faecal samples of dogs suspected of CPV infection.

Cytomegalovirus positive ulcerative colitis:A single center experience and literature review

AIM:To compare the clinical outcome of cytomegalovirus(CMV)-positive ulcerative colitis(UC) patients with and without antiviral therapy.METHODS:This was a retrospective case-controlled study.The database of UC patients in our institution was scanned for documented presence of CMV on colonic biopsies.Demographics,clinical data,endoscopy findings and pathology reports were extracted from the patients' charts and electronic records.When available,the data from colonoscopies preceding and following the diagnosis of colonic CMV infection were also ex-tracted.The primary outcomes of the study were colectomy/death during hospitalization and the secondary outcomes were colectomy/death through the course of the follow-up.RESULTS:Thirteen patients were included in the study,7(53.5%) of them were treated with gancyclovir and 6(46.5%) were not.Patients treated with antivirals presented with a more severe disease and 57% of them were treated with cyclosporine or infliximab before initiation of gancyclovir,while none of the patients without antivirals required rescue therapy.One patient died and another patient underwent urgent colectomy during hospitalization,both of them from the gancyclovir-treatment group.For the entire follow-up time(13 ± 13 mo),a total of 3 colectomies and one death occurred,all among the antiviral-treated patients(for colectomy:3/7 vs 0/6 patients,P = 0.19;for combined adverse outcome:4/7 vs 0/6 patients,P = 0.07).In 9/13 patients,immunohistochemistry for CMV was performed on biopsies obtained during a subsequent colonoscopy and was positive in one patient only.CONCLUSION:Gancyclovir-treated patients had a more severe disease and outcome,probably unrelated to antiviral therapy.Immunohistochemistry-CMV-positive patients with mild disease may recover without antiviral therapy.

Epstein-Barr virus is associated with gastric carcinoma: The question is what is the significance?

AIM: To examine the possible role of the Epstein- Barr Virus (EBV) in the development of gastric adenocarcinoma (GC). It is unclear whether EBV is involved in GC development or is a consequence of gastric inflammation secondary to immunosuppressive treatments. METHODS: A systematic review was carried out of all published observational studies on the temporal association between EBV and GC, with a view to determine a causal relationship. RESULTS: The present study showed that the worldwide crude prevalence of EBV in gastric adenocarcinoma was 8.29%. The prevalence varied from 7.08% for intestinal type and 9.82% for diffuse type of GC. It was observed that Western and Central Asian countries had a significantly higher frequency of EBV positive cases compared to South-Eastern countries. America had the highest EBV-GC prevalence whereas Europe had the lowest. CONCLUSION: The present review has demonstrated a high prevalence of EBV in gastric adenocarcinoma. However, studies designed to assess a temporal relationship and histological association using sensitive techniques should be carried out to establish the role of EBV in GC carcinogenesis.

Compartmentalization of hepatitis B virus: Looking beyond the liver

Hepatitis B virus(HBV) is classically considered to be hepatotropic, but accumulating evidences strongly support its extra-hepatotropic nature too. HBV nucleicacids and proteins have long been reported in a variety of extra-hepatic tissues. Of these, HBV has been studied in details in the peripheral blood mononuclear cells(PBMCs), due to its accessibility. From these studies, it is now well established that PBMCs are permissive to HBV infection, replication, transcription and production of infective virions. Furthermore, molecular evolutionary studies have provided definite evidences towards evolution of HBV genome in PBMCs, which is independent of evolution occurring in the liver, leading to the emergence and selection of compartment specific escape variants or drug resistant strains. These variants/resistant strains of HBV remain restricted within the PBMCs and are rarely detected in the serum/plasma. In addition, HBV infected PBMCs have been reported to be directly transmitted through intrauterine modes, and this infection does not correlate significantly with serum HBV surface antigen or HBV DNA markers. This editorial briefly reviews the current knowledge on this topic, emphasizes and delineates the gaps that are required to be filled to properly understand the biological and clinical relevance of extrahepatic tropism of HBV.

Virological response and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus coinfection

AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus(HCV-HIV) coinfected patients in a real life setting. METHODS: Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin(Peg IFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database(Nadis&#174;). Liver fibrosis was measured by elastometry(Fibroscan&#174;) with the following cut-off values: F0-F1: < 7.1 k Pa, F2: 7.1-9.5 k Pa, F3: 9.5-14.5 k Pa, F4: ≥ 14.5 k Pa. The proportion of patients with sustained virological response(SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described. RESULTS: Forty-one patients were included: 13(31.7%) patients were HCV-treatment na?ve, 22(53.7%) had advanced liver fibrosis or cirrhosis(Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them(83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia(88%) and rash(25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment. CONCLUSION: Telaprevir and boceprevir retain their place among potential treatment strategies in HIVHCV coinfected patients including those with advanced compensated liver disease and who failed previous Peg IFN/RBV therapy.

Production and application of recombinant haemagglutinin neuraminidase of Newcastle disease virus

Objective:To discuss the possibility of expressing the haemagglutinin-neuraminidase（HN） protein in prokaryotic system such as Escherichia coli（E.coli） cells by cloning the full length HN gene.Methods:The full length HN gene of Newcastle Disease Virus（NDV） of size 1 734 bp was preciously isolated by RT-PCR.The sequence was assessed and submitted to Nucleic Acid Databank（NCBI） and the gene ID was EU215390.1 after cloning and sequencing.Now the assessed HN gene was subcloned into pET 32 a+ expression vector for production the HN protein in E.coli, BL21（DE3） PLYSS cells following standard protocols.The crude lysate protein from the induced positive clone was size assessed by sodium dodecyl sulfale-polyacrylamide gel electrophoresis （SDS-PAGE） and their haemagglutination（HA） property against chicken RBC was assessed by standard micro HA test.Results:The molecular size of the full HN gene of NDV as assessed by cloning and digesting the positive clone to release the insert was 1.7 kb.The expressed protein in both crude and pure form was assessed to be 63 kDa and 81 kDa,respectively.The HA activity of the crude protein of the positive clone was 1 in 40.Conclusions:This finding indicates that the fusion protein retains the biological activity of native protein in the crude form and therefore could be used as a diagnostic reagent for antibody detection and for routine assessment of immune status in commercial layer forms.

Role of RNA secondary structure in emergence of compartment specific hepatitis B virus immune escape variants

AIM To investigate the role of subgenotype specific RNA secondary structure in the compartment specific selection of hepatitis B virus(HBV)immune escape mutations.METHODS This study was based on the analysis of the specific observation of HBV subgenotype A1 in the serum/plasma,while subgenotype A2 with G145R mutation in the peripheral blood leukocytes(PBLs).Genetic variability found among the two subgenotypes was used for prediction and comparison of the full length pregenomic RNA(pgRNA)secondary structure and base pairings.RNA secondary structures were predicted for 37℃using the Vienna RNA fold server,using default parameters.Visualization and detailed analysis was done using RNA shapes program.RESULTS In this analysis,using similar algorithm and conditions,entirely different pgRNA secondary structures for subgenotype A1 and subgenotype A2 were predicted,suggesting different base pairing patterns within the two subgenotypes of genotype A,specifically,in the HBV genetic region encoding the major hydrophilic loop.We observed that for subgenotype A1 specific pgRNA,nucleotide 358U base paired with 1738A and nucleotide 587G base paired with 607C.However in sharp contrast,in subgenotype A2 specific pgRNA,nucleotide 358U was opposite to nucleotide 588G,while 587G was opposite to 359U,hence precluding correct base pairing and thereby lesser stability of the stem structure.When the nucleotides at 358U and 587G were replaced with 358C and 587A respectively(as observed specifically in the PBL associated A2 sequences),these nucleotides base paired correctly with 588G and 359U,respectively.CONCLUSION The results of this study show that compartment specific mutations are associated with HBV subgenotype specific alterations in base pairing of the pgRNA,leading to compartment specific selection and preponderance of specific HBV subgenotype with unique mutational pattern.

Long-term protection against dengue viruses in mice conferred by a tetravalent DNA vaccine candidate

DEAR EDITOR,The development of an effective tetravalent vaccine against dengue viruses(DENVs)has become a world priority.We previously showed that four monovalent dengue DNA vaccines expressing premembrane(prM)and envelope(E)proteins displayed effective protection against corresponding challenges in mice.Thus,to elucidate the overall immunity and persistence of the tetravalent formulation(TetraME),we evaluated the humoral and cellular immune responses as well as the long-term protection in the current study.TetraME-immunized mice displayed increased production of Th1/Th2-typed cytokines upon stimulation with heterologous DENV antigens.Moreover,high levels of tetravalent DENV antibodies and sterilized immunity were detected long-term(30 weeks after immunization).These findings provide feasible validation for the potential utility of this vaccine formulation.

Special features of SARS-CoV-2 in daily practice

The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan,China in December 2019.Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines,based on scientific evidence and experts’opinions with clinical experience,are constantly being updated.On January 30,2020,the World Health Organization declared the SARS-CoV-2 outbreak as a"Public Health Emergency of International Concern".The total lack of immune protection brought about a severe spread of the contagion all over the world.For this reason,diagnostic tools,patient management and therapeutic approaches have been tested along the way,in the desperate race to break free from the widespread infection and its fatal respiratory complications.Current medical knowledge and research on severe and critical patients’management and experimental treatments are still evolving,but several protocols on minimizing risk of infection among the general population,patients and healthcare workers have been approved and diffused by International Health Authorities.

Clinical impact of hepatitis B and C virus envelope glycoproteins

Chronic infection by either hepatitis B virus(HBV)or hepatitis C virus(HCV)share epidemiological characteristics with risks for development of severe complications such as liver cirrhosis and hepatocellular carcinoma.HBV and HCV also share a high genetic variability. Among highly variable regions,viral genes encoding surface proteins(hepatitis B surface antigen,E1/E2 HCV glycoproteins)play key roles in the stimulation of the host-related immune response and viral entry into hepatocytes.Specific segments of HBV envelope proteins(preS1,"a"determinant)are crucial in the entry process into permissive cells.HCV entry is a complex multistep process involving multiple cell cofactors (glycosaminoglycans,low density lipoprotein receptor, SR-B1,CD81,claudin-1,occludin,EGFR,EphA2)in the interaction with HCV E1/E2 envelope glycoproteins.In vitro both viruses can be controlled by antibody-me-diated neutralization targeting viral envelope,also essential in preventing HBV infection in vivo as observed through successful vaccination using HBs antigen.But preventive vaccination and/or therapeutic pressure can influence HBV and HCV variability.For HBV,the patterns of antiviral drug resistance in chronic hepatitis are complex and the original pol/S gene overlap has to be taken into account.Treatment-induced HBV mutations in pol could indeed generate S mutants with subsequent modified antigenicity or increased cancer induction.Variability of HBV and HCV envelope proteins combining high exposure to selective pressures and crucial functional roles require investigation in the context of diagnostic,vaccination and treatment tools.In this editorial a synthesis is performed of HBV and HCV envelope properties at the entry step and as antigenic proteins,and the subsequent clinical impact.

Cell culture systems for the hepatitis C virus

Since the discovery of HCV in 1989, the lack of a cell culture system has hampered research progress on this important human pathogen. No robust system has been obtained by empiric approaches, and HCV cell culture remained hypothetical until 2005. The construction of functional molecular clones has served as a starting point to reconstitute a consensus infectious cDNA that was able to transcribe infectious HCV RNAs as shown by intrahepatic inoculation in a chimpanzee. Other consen- sus clones have been selected and established in a hu- man hepatoma cell line as replicons, i.e. self-replicating subgenomic or genomic viral RNAs. However, these repli- cons did not support production of infectious virus. Inter- estingly, some full-length replicons could be established without adaptive mutations and one of them was able to replicate at very high levels and to release virus particles that are infectious in cell culture and in vivo. This new cell culture system represents a major breakthrough in the HCV field and should enable a broad range of basic and applied studies to be achieved.

Case of acute hepatitis E with concomitant signs of autoimmunity

Sporadic cases of acute viral hepatitis E have been described in developed countries, despite the more common occurrence in endemic areas and developing countries. We present the case of a 58 years old Portuguese female, with no epidemiological relevant factors, admitted with acute hepatitis with positive anti-nuclear antibodies, anti-smooth muscle antibody and high serum gamma globulin (> 1.5 fold increase). Serologies for hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, hereditary sensory neuropathy and varicella zoster virus were negative. Liver biopsy histology revealed changes compatible with autoimmune hepatitis. Prednisolone and azathioprine was started. She tested positive for immunoglobulin M anti hepatitis E virus (HEV) with detectable viremia by reverse transcription polymerase chain reaction (RT-PCR) technique. HEV-RNA was confirmed throughRT-PCR in a liver specimen, establishing the diagnosis of acute hepatitis E. Immunosuppression was stopped. She clinically improved, with resolution of laboratory abnormalities. Therefore, we confirmed acute hepatitis E as the diagnosis. We review the literature to elucidate about HEV infection and its autoimmune effects.

Genome Sequences of COVID-19 from Jordanian Patients in Comparison with the Global Pandemic Strains and the Transmission Route

In this research study, we reported a pioneer investigation on the phylogenetic profile of genomic sequences and the prevalence of COVID-19 strains in Jordan;in comparison with global strains, as part of concerted global efforts in combating the COVID-19 pandemic. A total of 28 genome sequences of the hCoV-19/Jordan strain were employed in this study. The phylogenetic analysis of the genome sequences of hCoV-19/Jordan strain, which was conducted on the databases of NCBI and GASAID revealed that the hCoV-19/Jordan strain belongs to the G, V, and S clades with distribution coverage rates of 89%, 7% and 4%, respectively. Comparison of the hCoV-19/Jordan clades with global clades distribution profile showed evidently and conclusively, a unique pandemic profile of multiple geographical sources of COVID-19, imported into Jordan primarily through cryptic means from European countries (UK, Belgium, Sweden, Russia) and Morocco, which are entry points into Jordan. This is due to the reciprocal heavy air traffic route between Jordan and the capitals of these European countries, with Morocco being the primary entry point into Jordan. The results of this study represent a marked addition to investigations on the prevalence rate of the hCovid-19/Jordan strain in comparison to the global strains sequences, and provides a better understanding on comparative diagnosis technique for COVID-19 worldwide. Phylogenetic analysis of the top 100 and top 10 taxonomic trees revealed almost identical homology (99.98% - 100%) between hCoV-19/Jordan strain and the strains that broke out in Wuhan, the MT642226.1. Furthermore, it can be inferred that there was no marked change in the virus mutation that occurred during the period of this study taking into cognizance the fact that there was identical homology (99.98% - 100%) among the 28 sequences of hCoV-19/Jordan strains. Similarly, all sequences of the Jordanian strains of hCoV-19/Jordan were compared to the England and American strains and showed identical homology of (99.98% - 100%).