Multiplex Rapid Test with Acceptable Diagnosis Performance as a Solution to Increase Diagnosis of Hepatitis B and C Viruses in Pregnant Women in an Area of High Prevalence of Both Hepatitis Viruses Associated with HIV

Background and Objective: HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) are very widespread in the world, however, less than 20% of the people affected are diagnosed and treated. This study aimed to determine the prevalence of HIV, HCV and HBV co-infections in pregnant women at Bangui Community University Hospital and the cost of screening. Methods: A cross-sectional study involving consenting pregnant women who came for antenatal care was performed. HIV, HCV antibodies and HBV antigens were detected using Exacto Triplex? HIV/HCV/HBsAg rapid test, cross-validated by ELISA tests. Sociodemographic and professional data, the modes of transmission and prevention of HIV and both hepatitis viruses were collected in a standard sheet and analyzed using the Epi-Info software version 7. Results: Pregnant women aged 15 to 24 were the most affected (45.3%);high school girls (46.0%), and pregnant women living in cohabitation (65.3%) were the most represented. Twenty-five (16.7%) worked in the formal sector, 12.7% were unemployed housewives and the remainder in the informal sector. The prevalence of HIV, HBV, and HCV viruses was 11.8%, 21.9% and 22.2%, respectively. The prevalence of co-infections was 8.6% for HIV-HBV, 10.2% for HIV-HCV, 14.7% for HBV-HCV and 6.5% for HIV-HBV-HCV. All positive results and 10% of negative results by the rapid test were confirmed by ELISA tests. The serology of the three viruses costs 39,000 FCFA (60 Euros) by ELISA compared to 10,000 FCFA (15.00 Euros) with Exacto Triplex? HIV/HCV/AgHBs (BioSynex, Strasbourg, France). Conclusion: The low level of education and awareness of hepatitis are barriers to development and indicate the importance of improving the literacy rate of women in the Central African Republic (CAR). Likewise, the high prevalence of the three viruses shows the need for the urgent establishment of a national program to combat viral hepatitis in the CAR.

Real-world utility of serological tests in patients with suspected scrub typhus in the Republic of Korea:A single-center,retrospective,observational study

Objective:Serological tests are widely used for scrub typhus diagnosis;however,their limitations are evident.This study aims to assess their practical value in clinical settings.Methods:We analyzed the data of adult patients with suspected scrub typhus who visited a tertiary care hospital in the Republic of Korea from September to December from 2019 to 2021.The included patients had an acute fever and at least one of the following ten secondary findings:myalgia,skin rash,eschar,headache,thrombocytopenia,increased liver enzyme levels,lymphadenopathy,hepatomegaly,splenomegaly,and pleural effusion.The diagnoses were grouped as scrub typhus or other diseases by two infectious disease physicians.Results:Among 136 patients who met the eligibility criteria,109 had scrub typhus and 27 had different diseases.Single and paired total antibodies using immunofluorescence assay(IFA),and total antibodies using immunochromatography-based rapid diagnostic testing(ICT)were measured in 98%,22%,and 75%of all patients,respectively.Confirmation using paired samples for scrub typhus was established at a median of 11[interquartile range(IQR)10-16]days following the first visit.Among the 82 admitted patients,the median admission time was 9(IQR 7-13)days.According to IFA,58(55%)patients with scrub typhus had total immunoglobulin titers≥1:320,while 23(85%)patients with other disease had titers<1:320.Positive ICT results were observed in 64(74%)patients with scrub typhus and 10(67%)patients with other diseases showed negative ICT results.Conclusions:Serological testing for scrub typhus is currently insufficient for decision-making in clinical practice.

Correction to“Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil”

Correction to“Freire de Melo F,Martins Oliveira Diniz L,Nélio Januário J,Fernando Gonçalves Ferreira J,Dórea RSDM,de Brito BB,Marques HS,Lemos FFB,Silva Luz M,Rocha Pinheiro SL,de Magalhães Queiroz DM.Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil.World J Exp Med 2022;12(5):100-103[PMID:36196438 DOI:10.5493/wjem.v12.i5.100]”.In this article,we identified an issue with the“Acknowledgments”section.Here,we then provide a recognition section for our supporting institutions.

Study on the Application Value of Liver Function and Serological Index Levels in the Diagnosis of Fatty Liver

Objective:To explore the application value of liver function and serological index detection in diagnosing fatty liver.Methods:Ninety patients with fatty liver disease(disease group)and ninety healthy subjects(healthy group)were selected as the subjects of this study.They all underwent liver function index testing and serological index testing.Test results were compared,and the diagnostic accuracy of single and combined tests was evaluated.Results:Liver function indicators of patients in the disease group were higher than those in the healthy group,with severe patients exhibiting higher levels than moderate patients and mild patients(P<0.05).Serological indicators in patients in the disease group were higher than those in the healthy group,with severe patients showing higher levels than moderate patients and mild patients(P<0.05).The diagnostic accuracy of liver function index testing was higher than that of serological index testing,and the accuracy of combined testing was higher than that of single testing(P<0.05).Conclusion:In diagnosing fatty liver,combining liver function testing and serological testing enables the initial diagnosis of the disease and facilitates the accurate assessment of its severity.

Analysis of Clinical Characteristics and Diagnostic Value of Fungal Serology in Patients with Invasive Candidiasis

Objective: To evaluate the diagnostic value of (1 - 3)-β-D glucan and mannan assay for invasive candidiasis. Methods: A retrospective study was conducted on 32 cases in the disease group (18 proven invasive candidiasis and 14 probable invasive candidiasis) and 48 cases in the control group. The subjects were recruited from January 2018 to March 2019 in Clinical Laboratory of Hainan General Hospital. All subjects were detected by (1 - 3)-β-D glucan and mannan assay. Results: The mean concentration of (1 - 3)-β-D glucan in the disease group was 97.45 (43.23, 224.35) pg/ml and it was significantly higher than the mean concentration of the control group which was 49.85(41.91, 56.07) pg/ml (P = 0.005). The mean concentration of mannan in the disease group and the control group were 161.36 (34.96, 224.49) pg/ml and 25.80 (25.00, 29.31) pg/ml, respectively, which were significantly different (P < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of (1 - 3)-β-D glucan assay were 59.38%, 89.58%, 79.17%, 76.79%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of mannan assay were 65.63%, 95.83%, 91.30%, 80.70%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of combination of two types of assays were 81.25%, 85.42%, 78.79% and 87.23%, respectively. Conclusions: Combination of (1 - 3)-β-D glucan and mannan assay can improve diagnostic specificity and it has essential clinical diagnostic value for invasive candidiasis.

Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil

Qualitative antibody tests are an easy,point-of-care diagnostic method that is useful in diagnosing coronavirus disease 2019,especially in situations where reverse transcription-polymerase chain reaction is negative.However,some factors are able to affect its sensitivity and accuracy,which may contribute to these tests not being used as a first-line diagnostic tool.

Three-dimensional models of antigens with serodiagnostic potential for leprosy:An in silico study

BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.

Temporal pattern of humoral immune response in mild cases of COVID-19

BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporality of reinfection,provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and consequently helps in global public health and vaccination strategy.Among the patients who became infected with SARS-CoV-2,the majority who did not progress to death were those who developed the mild COVID-19,so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G(IgG)in mild cases of COVID-19.METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction(RT-qPCR)-positive volunteers from the municipality of Toledo/Paraná/Brazil,underwent two distinct serological tests,enzyme-linked immunosorbent assay,and detection of anti-nucleocapsid IgG.Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021.All assays were performed in duplicate and the manufacturers'recommendations were strictly followed.The data were statistically analyzed using multiple logistic regression;the variables were selected by applying the P<0.05 criterion.RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo.The time periods when the highest number of participants with detectable IgG was observed were 1,2 and 3 mo.It was observed that 9.42%of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57%were also IgG negative at less than 1 mo.At 5 mo,3.14%of volunteers were IgG negative,and at 6 or 7 mo,1 volunteer(0.52%)had no detectable IgG.During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study,no statistical significance was observed for any association analyzed.Moreover,considering the age category between 31 and 59 years as the exposed group,the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older,showing that in both age categories there was no association between the pair of variables analyzed.Regarding chronic disease,the exposure group consisted of the participants without any comorbidity,so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.CONCLUSION A temporal pattern of IgG response was not observed,but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.

Perinatal transmission in infants of mothers with chronic hepatitis B in California

To evaluate maternal hepatitis B virus (HBV) DNA as risk for perinatal HBV infection among infants of HBV-infected women in California. METHODSRetrospective analysis among infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received post vaccination serologic testing (PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen (HBeAg) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/mL, a 5:1 ratio of cases to controls and a two-sided confidence level of 95%. RESULTSA total of 17687 infants were born to HBsAg positive mothers in California between Jan 1 2005 and Dec 31, 2011. Among 11473 infants with PVST, only 125 (1.1%) were found to be HBV infected. Among these infected infants, lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis (PEP) occurred in only 9 infants. However, PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBeAg and HBV DNA level, case-control analysis found HBeAg positivity (70.4% vs 28.9%, OR = 46.76, 95%CI: 6.05-361.32, P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/mL (92.6% vs 18.5%, OR = 54.5, 95%CI: 12.22-247.55, P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression, maternal HBV DNA level ≥ 2 × 107 IU/mL was the only significant independent predictor of perinatal HBV infection. CONCLUSIONIn California, transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/mL is associated with high risk of perinatal infection.

Biology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the humoral immunoresponse:a systematic review of evidence to support global policy-level actions and research

Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.

Hepatitis C virus: Virology, diagnosis and management ofantiviral therapy

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.

Detection of anti-Helicobacter pyloriantibodies in serum and duodenal fluid in peptic gastroduodenal disease

AIM:To study the diagnosis of Helicobacter pylori(H pylori) infection through the determination of serum levels of anti- H pylori IgG and IgA antibodies,and the levels of anti-H pylori IgA antibodies in duodenal fluid. METHODS:Data were collected from 93 patients submitted to upper digestive endoscopy due to dyspeptic symptoms. The patients were either negative(group A)or positive (group B)to H pylori by means of both histological detection and urease tests.Before endoscopy,peripheral blood was collected for the investigation of anti-H pylori IgG and IgA antibodies.To perform the urease test,biopsies were obtained from the gastric antrum.For the histological evaluation,biopsies were collected from the gastric antrum (greater and lesser curvatures)and the gastric body. Following this,duodenal fluid was collected from the first and second portions of the duodenum.For the serological assaying of anti-Hpylori IgG and IgA,and anti-Hpylori IgA in duodenal fluids,the ELISA method was utilized. RESULTS:The concentration of serum IgG showed sensitivity of 64.0%,specificity of 83.7%,positive predictive value of 82.0%,negative predictive value of 66.6% and accuracy of 73.1% for the diagnosis of H pylori infection.For the same purpose,serum IgA showed sensitivity of 72.0%, specificity of 65.9%,positive predictive value of 72.0%, negative predictive value of 67.4% and accuracy of 69.8%. If the serological tests were considered together,i.e.when both were positive or negative,the accuracy was 80.0%, sensitivity was 86.6%,specificity was 74.2%,positive predictive value was 74.2% and negative predictive value was 86.6%.When values obtained in the test for detecting IgA in the duodenal fluid were analyzed,no significant difference(P=0.43)was observed between the values obtained from patients with or without H pylori infection. CONCLUSION:The results of serum IgG and IgA tests for H pylori detection when used simultaneously,are more efficient in accuracy,sensitivity and negative predictive value, than those when used alone.The concentration of IgA antibodies in duodenal fluid is not useful in identifying patients with or without H pylori.

Complexities of diagnosis and management of COVID-19 in autoimmune diseases:Potential benefits and detriments of immunosuppression

Recent advances in our understanding of coronavirus disease 2019(COVID-19)and the associated acute respiratory distress syndrome might approximate the cytokine release syndrome of severe immune-mediated disease.Importantly,this presumption provides the rationale for utilization of therapy,until recently reserved mostly for autoimmune diseases(ADs),in the management of COVID-19 hyperinflammation condition and has led to an extensive discussion for the potential benefits and detriments of immunosuppression.Our paper intends to examine the available recommendations,complexities in diagnosis and management when dealing with patients with ADs amidst the COVID-19 crisis.Mimicking a flare of an underlying AD,overlapping pathological lung patterns,probability of higher rates of false-positive antibody test,and lack of concrete data are only a part of the detrimental and specific characteristics of COVID-19 outbreak among the population with ADs.The administration of pharmaceutical therapy should not undermine the physical and psychological status of the patient with the maximum utilization of telemedicine.Researchers and clinicians should be vigilant for upcoming research for insight and perspective to fine-tune the clinical guidelines and practice and to weigh the potential benefits and detrimental effects of the applied immunomodulating therapy.

An outlook on coronavirus disease 2019 detection methods

Diagnostic testing plays a fundamental role in the mitigation and containment of coronavirus disease 2019(COVID-19),as it enables immediate quarantine of those who are infected and contagious and is essential for the epidemiological characterization of the virus and estimating the number of infected cases worldwide.Confirmation of viral infections,such as COVID-19,can be achieved through two general approaches:nucleic acid amplification tests(NAATs)or molecular tests,and serological or antibody-based tests.The genetic material of the pathogen is detected in NAAT,and in serological tests,host antibodies produced in response to the pathogen are identified.Other methods of diagnosing COVID-19 include radiological imaging of the lungs and in vitro detection of viral antigens.This review covers different approaches available to diagnosing COVID-19 by outlining their advantages and shortcomings,as well as appropriate indications for more accurate testing.

Syphilis Serologic Follow-up After Regular Treatment

Objective： To understand the changes in syphilis serology after regular treatment. Methods： Patients with clinical evidence and credible medical history of syphilis were treated regularly. Their serologic tests were followed for two years. Results： At the end of half a year, 22.95% of patients had a negative USR but 26.23% remained positive even after 2 years. More than 3% of patients had a negative FTA-ABS result. These patients tended to be under 40 with a disease course of less than 2 years. Conclusion： The resolution rate was high for patients who were young, had a shorter course of disease and reacted strongly to the infection. In patients older than 40 with a long course of disease, the resolution rate was low.

Zika virus:A review of literature

Zika virus(ZIKV) has two lineages:African and Asian.Mosquito-borne flaviviruses are thought to replicate initially in dendritic cells and then spread to lymph nodes and the blood stream.Risk for infection through blood transfusion,sexual practices and perinatal transmission exists.The possible routes of perinatal transmission are during delivery,breastfeeding and by close contact between the mother and her newborn.Also,mucocutaneous exposures to the virus by infected blood or monkey bite,organ transplantation or hemodialysis are the other routes of ZIKV transmission.There are two types of ZIKV infection;Zika fever and congenital infection.Clinical presentation of Zika fever varies from asymptomatic infections to a self-limiting febrile disease with low grade fever,conjunctivitis,maculopapular rash,headache,retro-orbital pain and arthritis/arthralgia with periarticular edema,myalgia,vertigo,vomiting and asthenia.This clinical feature could be mistaken for dengue or chikungunya fevers.Microcephaly is the most important and frequently reported clinical picture of suspected congenital Zika syndrome.Laboratory tests are needed for diagnosis of ZIKV infection,because there is no known pathognomonic clinical,biochemical or radiological features.RT-PCR is the most wellliked assay.Serum samples are tested by immunoglobulin G ELISA with ZIKV antigen.Samples are also tested by immunoglobulin M ELISA.There is no certified vaccine or therapeutic medication.In asymptomatic or uncomplicated patients,treatment is not necessary.

Serological Detection of Tomato Pepino mosaic virus in Morocco

Pepino mosaic virus （PepMV）, monopartite RNA virus, 6,500 pb, belonging to Flexiviridae and Potexvirus group, is highly infectious and easily transmissible. Its economic impact is major for the tomato producer＇s countries. Prevention, based on early virus detection is the only effective control measure. Monoclonal antibodies appeared to be very useful tool. The authors used for the production of monoclonal antibodies hybridomas technique, by fusing spleen cells of immunized BALB/c mice to PepMV and SP2/O cancerous cells. The aim of this work is to produce hybridomas producers of Mab that could be used for ELISA in Morocco. At the same time, these efforts will serve to decrease expenses of producers concerning phytosanitory control. We obtained 16 hybridomas lines producers of Mab specific for PepMV. They were tested for efficiencies in ELISA and two lines were retained for production of Mab on large scale （1B 11-G 10 and 5A l-G5）. Isotyping of these two lines showed that they are belonging to IgG 1 class and easily purified by affinity chromatography in agarose column by protein A. The conjugation of these two antibodies to alkaline phosphatase has been verified by DAS-ELISA. These antibodies will enable to diagnose the disease from infected tomato plants, integrating several serological tests to control it and target the actions of struggles.

Compliance among infants exposed to hepatitis B virus in a post-vaccination serological testing program in four provinces in China

Background:Mother to child transmission of hepatitis B virus(HBV)remains the most common form of HBV infection in China.Prevention of HBV vertical transmission involves timely administration of the complete hepatitis B vaccine(HepB)series and hepatitis B immunoglobulin.Post-vaccination serological testing(PVST)is utilized to determine an infant's outcome after HBV exposure and completion of HepB series.We aim to determine the frequency of compliance with a PVST testing cascade for HBV infected mothers and analyze factors associated with infant lost to follow up(LTFU).Methods:We conducted a retrospeaive cohort review of previously collected data in Fujian,Jiangxi,Zhejiang and Chongqing provinces in China from 1 June 2016-31 December 2017.The study population included all HBV-exposed infants and their mothers.SAS software was used for statistical analyses.Bivariate and multivariate regression analyses(presented in odds ratio[OR]with 95%confidence intervals[CI])were used to compare the proportional differences of factors associated with PVST not being completed.Results:Among enrolled 8474 target infants,40%of them transferred out of the study provinces without further information and 4988 were eligible for PVST.We found 20%(994)of infants were not compliant with the testing cascade:55%of LTFU occurred because parents refused venous blood sample collection or failure of sample collection in the field,16%transferred out after 6 months of age,and 10%of families chose to have independent,confidential PVST completed without reporting results.High PVST noncompliance rates were more likely to be from Fujian(aOR=17.0,95%CI:9.7-29.9),Zhejiang(aOR=5.7,95%Cl:3.2-10.1)and Jiangxi(aOR=1.9,95%CI:1.0-3.4),and from HBV e antigen positive mother(aOR=1.2,95%CI:1.1-1.4).Conclusions:This study found that the LTFU rate reached 20%in PVST program,which was a significant problem.We recommend implementing a national elearonic information system for tracking HBV at risk mother-infant pairs;encourage further research in developing a less invasive means of completing PVST,and take effective measures nationally to reduce HBV stigma.Without reducing the loss to follow up rate among infants eligible for PVST,elimination of vertical HBV transmission will be impossible.

An intelligent serological SERS test toward early-stage hepatocellular carcinoma diagnosis through ultrasensitive nanobiosensing

Early or very early detection of hepatocellular carcinoma(HCC)is an effective means to resolve the low cure rates,but there currently lacks a method that fulfills clinical requirements.One of the most prospective approaches to detecting early-stage HCC is directly testing a compendium of disease-relevant biomolecules contained within human serum through surface-enhanced Raman scattering(SERS)nanobiosensing and recognizing the biomolecular patterns.We report a novel Si-based bimetallic nanoensembles-functionalized SERS substrate(its analytical enhancement factor reaches 1.47×10^(12))and introduce an ultrasensitive nanobiosensing for capturing the subtle characteristic changes in SERS spectra caused by HCC,hepatitis B,or cirrhosis.Toward early diagnosis,we created an intelligent serological test with this nanobiosensing and the deep learning algorithm to gain key biomolecular phenotypes of early-stage HCC.Using clinical samples from four target populations(normal,HCC,cirrhosis,and hepatitis B),the proof-of-principle result indicates that the test yielded a predictive accuracy of 98.75%on a held-out dataset(randomly drew 4 out of 28 samples per population).On the same held-out dataset,the sensitivity and specificity of the test were both 100%for distinguishing HCC.Such a new-concept liquid biopsy could provide an opportunity for early diagnosis of HCC.

Meta-analysis of the immunogenicity of standard and booster SARS-CoV-2 vaccination in patients with chronic liver disease and post-liver transplantation

Aims:Patients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019(COVID-19)than healthy individuals,and vaccination against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an effective prevention strategy.This metaanalysis aimed to assess the effectiveness and safety of SARS-CoV-2 vaccines in patients with chronic liver disease(CLD)and post-liver transplantation(LT).Methods:The PubMed,Embase,and Cochrane databases were searched.A random-effects model meta-analysis was used to determine the seropositivity rates of SARS-CoV-2 antibodies,odds ratio(OR)compared with healthy controls(HC),risk ratio(RR)between the booster and standard vaccination regimen,and the rate of adverse reactions(ADR).Results:In the standard vaccination regimen analysis,17 controlled articles were included for effectiveness analysis,and six articles for ADR analysis.The pooled seropositivity rates of SARS-CoV-2 antibodies in patients with CLD and post-LT were 93.3%(95%confidence interval[CI]:89.0%-97.6%)and 69.1%(95%CI:63.0%-75.3%),respectively.Both rates were lower than those in HC(p<0.001).The differences remained significant after sorting by detection interval,vaccine type,antibody type,or CLD type.LT recipients showed much lower seropositivity rates of antibodies than patients with CLD(69.1%vs.93.3%)or HC(OR:0.055).The pooled total ADR rate of patients was 24.0%(95%CI:16.2%-31.8%).In the booster vaccination regimen analysis,11 prospective studies were enrolled,and the seropositivity rates of antibodies after the booster dose were increased by 27%compared with those of the standard vaccination regimen(RR:1.27,95%CI:1.15-1.41,p<0.001).Conclusion:Patients with CLD and post-LT can gain protection against COVID-19 from standard vaccines,demonstrating a potentially weaker immunogenic response than HC.Booster vaccines can compensate for this deficiency.Therefore,patients with CLD and post-LT should be prioritized for receiving the COVID-19 booster vaccine.