Epidemiological and clinical insights into the enterovirus D68 upsurge in Europe 2021/22 and the emergence of novel B3-derived lineages, ENPEN multicentre study.

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages.

Prevalence, clinical and virological characteristics and short-term prognosis of hepatitis delta infection among patients with HIV/HBV in Nouakchott, Mauritania.

Patients living with HIV infection (PLWH) are at risk of acquiring HBV and HDV. The present study aimed to determine the prevalence and characteristics of HIV-HDV-HBV tri-infection in comparison with HIV-HBV coinfection and to estimate severities and outcomes of associated liver diseases in Mauritanian PLWH. Two-hundred-ninety-two consecutive HBsAg-positive PLWH were included (mean age: 37 years). Clinical data were recorded. Anti-HDV antibodies, HBV and HDV viral loads (VLs) and genotype were determined. APRI, FIB-4 and FibroScan were performed to evaluate the severity of liver disease. The anti-HDV antibodies prevalence was 37% and HDV RNA was positive in 40.7% of patients. Genetic diversities were found with HDV genotype 1 (93%) and HBV genotypes D (42.5%) and E (38%). The HBV VL was detectable in 108 patients at inclusion, and mutations associated with HBV resistance were found in 20. For almost all variables studied, including FIB-4 and APRI scores, no significant differences were found between anti-HDV-Ab positive or negative patients. FibroScan examination, which was performed in 110 patients at end-of-follow-up showed higher, but NS values, in HDV positive patients. After a mean follow-up of 24.55 ± 8.01 months (n = 217 patients), a highly significant worsening of APRI and FIB-4 scores was found. Moreover, patients with HDV showed more severe liver disease progression despite an efficient therapy. In a substantial Mauritanian cohort of relatively young PLWH, we found high HDV prevalence and worsening liver disease. In high-risk countries, screening for HDV and providing appropriate follow-up and treatments are warranted in PLWH.

[Role of hepatitis B virus e protein and core protein in hepatocarcinogenesis]. / Rôle des protéines HBe et HBc du virus de l'hépatite B dans l'hépatocarcinogenèse.

Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC). However, the pathogenesis of HBV-mediated hepatocarcinogenesis is not clearly defined. Persistence of HBV infection is associated with HCC pathogenesis, and various HBV proteins appear to be involved in promoting this persistence. Currently available data suggest that the core protein, a structural component of the viral nucleocapsid, and the HBe protein, a non-structural HBV protein that can act as both a tolerogen and an immunogen, play a potential role in the development of HCC. Research shows that both proteins are capable of disrupting various pathways involved in liver carcinogenesis, including the sustenance of proliferative signaling, resistance to cell death, tumor-promoting inflammation and avoid immune destruction. This review summarizes the various signaling pathways by which HBc and HBe proteins (and their precursors) can promote hepatocarcinogenesis.

What is the true place of the SARS-CoV-2 rapid point-of-care antigen test in the hospital setting? Lessons learned from real life.

To assist in the clinical management of patients and to support infection control, we tested the use of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care antigen test (AgPOC) for unplanned hospitalization, coupled with a nucleic acid amplification test (NAAT) using specimens collected at the same time upon arrival. The aim of this study was to assess the performance of the AgPOC in this specific use compared to NAAT for SARS-CoV-2 diagnosis, in the context of the low prevalence of infection. For 5 months (between two peaks in France of the SARS-CoV-2 pandemic), all patients admitted who undertook the AgPOC/NAAT paired tests were included in the study. AgPOC performances were determined considering the clinical status and the delay of symptoms onset. NAAT and AgPOC results were available for 4425 subjects. AgPOC results showed a homogeneous specificity (>97%) but a low sensitivity at 45.8%. Considering the national guidelines, sensitivity dropped to 32.5% in cases of symptomatic patients with symptoms older than 5 days or more. This study shows the poor performance of AgPOC for entry screening of patients in hospitals. AgPOC may represent a useful tool in the hospital setting only if the use is restricted to patients with consistent symptoms less than 4 days old.

Comparison of performance between three SARS-CoV-2 molecular assays (Aptima™, Laboratory Developed Test-Fusion, and R-GENE®) with special attention to turnaround time, a key point in laboratory management.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of rapid diagnostic testing to identify individuals with SARS-CoV-2 infections and to limit the spread of the virus. Many molecular assays have become commercially available to cope with this surging demand for timely diagnosis of COVID-19 cases, but identifying individuals requires accurate diagnostic tools. We compared the performance of three molecular SARS-CoV-2 assays: Aptima™ SARS-CoV-2 assay running on the Panther system (Hologic), an in-house assay (Laboratory Developed Test, LDT) running on the Fusion module of the Panther Fusion system (LDT-Fusion; Hologic), and the R-GENE® SARS-CoV-2 assay (bioMérieux). In addition, we also evaluated the turnaround time. This parameter is crucial to managing the SARS-CoV-2 diagnosis and represents a key point in the quality management at the laboratory. Aptima™ and LDT-Fusion assays exhibited an excellent positive percent agreement (PPA) (100.0%), while the R-GENE® assay showed a slightly decreased PPA (98.2%). The Hologic assays have a higher throughput with less hands-on time than the R-GENE® assays (24-25 vs. 71 min). Both Hologic assays are used on a fully automated random-access testing system with on-demand testing capabilities that avoid run series, unlike the R-GENE® assay. Automated random-access testing systems should be preferred during periods of high SARS-CoV-2 prevalence.

A Pleiotropic Role of the Hepatitis B Virus Core Protein in Hepatocarcinogenesis.

Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC), which is the sixth most prevalent cancer among all cancers worldwide. However, the pathogenesis of HBV-mediated hepatocarcinogenesis is unclear. Evidence currently available suggests that the HBV core protein (HBc) plays a potential role in the development of HCC, such as the HBV X protein. The core protein, which is the structural component of the viral nucleocapsid, contributes to almost every stage of the HBV life cycle and occupies diverse roles in HBV replication and pathogenesis. Recent studies have shown that HBc was able to disrupt various pathways involved in liver carcinogenesis: the signaling pathways implicated in migration and proliferation of hepatoma cells, apoptosis pathways, and cell metabolic pathways inducing the development of HCC; and the immune system, through the expression and production of proinflammatory cytokines. In addition, HBc can modulate normal functions of hepatocytes through disrupting human host gene expression by binding to promoter regions. This HBV protein also promotes HCC metastasis through epigenetic alterations, such as micro-RNA. This review focuses on the molecular pathogenesis of the HBc protein in HBV-induced HCC.

A Highly Prevalent Polymorphism in the Core Region Impairs Quantification of Hepatitis B Virus (HBV) by the cobas TaqMan HBV Assay.

The high genetic variability of hepatitis B virus (HBV) can impair DNA quantification. Here, we investigate a major underquantification of HBV by the cobas TaqMan HBV assay (CTM; Roche). In France, between 2005 and 2017, HBV DNA was detected in 3,102 blood donations by use of the CTM (95% limit of detection [LOD95], 4.8 IU/ml). HBV strains were sequenced in the S region (LOD95, ∼30 IU/ml). Concordant (n = 120) and discordant (n = 45) samples were identified according to the agreement between the plasma viral load (pVL) determined by the CTM and sequencing; all samples were also quantified using the RealTime HBV assay (RTH; Abbott). The viral signature, cloning, and mutagenesis were used to characterize the polymorphism responsible for CTM misquantification. A CTM-RTH discordance (>1 log IU/ml) was found in 14/45 samples that had low pVLs and were successfully genotyped (pVLlow genoS+). PreC/C clones of concordant (C1, C2) and discordant (D1, D2) strains were used to challenge the CTM. Strains D1 and D2 were highly underquantified (42- and 368-fold). In clones, mutating the region corresponding to the CTM reverse primer from a discordant sequence to a concordant sequence restored the levels of quantification to 24% (D1→C1) and 59% (D2→C1) of theoretical levels, while mutating the sequence of a concordant strain to that of a discordant strain led to 78-fold (C1→D1) and 146-fold (C1→D2) decreases in quantification. Moreover, mutating positions 1961 and 1962 was enough to induce a 5-fold underquantification. We conclude that the CTM underestimates pVLs for HBV strains with mutations in the reverse primer target. Specifically, the polymorphism at nucleotides 1961 and 1962 is naturally present in 4.79 and 4.22% of genotype A and D strains, which are highly frequent in Europe, leading to a 5-fold decrease in quantification. Quantification using the new-generation Roche C4800 assay is not affected by this polymorphism.

Practical approach to method verification in plasma and validation in cerebrospinal fluid under accreditation using a flexible scope in molecular virology: setting up the HIV, HBV and HCV Aptima™ Quant Dx assays.

Background Our laboratory obtained the ISO 15189 accreditation for the plasmatic HIV-1, HBV and HCV viral load (VL) using the m2000 RealTime™ system, which was recently changed for the platform Panther®. Here, we discuss a strategy for performing method validation/verification very quickly. Methods We performed the mandatory (repeatability, internal quality assessment [IQA], measurement uncertainty [MU]) and optional technical verifications for CE/IVD assays using the flexible scope range A. We also performed the mandatory assays for the validation of HIV-1 VL in the cerebrospinal fluid (CSF) using the flexible scope range B. The change was checked by following up on the turnaround time (TAT). Results The coefficient of variation (CV%) for repeatability and IQA complied with the limit of 0.25 log. The MU results ranged from 0.04 to 0.25 log copies or IU/mL. The comparisons of methods showed excellent correlations (R2 = 0.96 for the three parameters) but a delayed centrifugation on HCV VL showed variations of up to 2 log IU/mL. An excellent linearity for HIV-1 in the CSF was obtained from 1.5 to 5 log copies/mL with R2 = 0.99. The TAT increased (84%-98%) in routine usage. Conclusions The three Aptima assays are well suited for routine laboratory use and can be integrated within less than 2 weeks in accordance with flexible scope range A. Our data allows us to confidently perform HIV-1 VL in CSF following flexible scope range B. Finally, we provide an organizational guide for flexible scope management in molecular virology within a short time frame.

A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases.

BACKGROUND AND GOAL: International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. STUDY: Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). RESULTS: OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. CONCLUSIONS: Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.

Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests.

BACKGROUND AND AIM: There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance. METHODS: We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeterV2G . RESULTS: Median follow-up was 2.8 years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P < 0.050). According to time-dependent AUROCs, the time period with optimal predictive performance was 2-3 years in patients with no/mild fibrosis, 1 year in patients with significant fibrosis, and <6 months in cirrhotic patients even in those with a model of end-stage liver disease (MELD) score <15. Patients were then randomly split in training/testing sets. In the training set, blood tests and LSM were independent predictors of all-cause mortality. The best-fit multivariate model included age, sex, LSM, and FibroMeterV2G with C-index = 0.834 (95% confidence interval, 0.803-0.862). The prognostic model for liver-related mortality included the same covariates with C-index = 0.868 (0.831-0.902). In the testing set, the multivariate models had higher prognostic accuracy than FibroMeterV2G or LSM alone for all-cause mortality and FibroMeterV2G alone for liver-related mortality. CONCLUSIONS: The prognostic durability of a single baseline fibrosis evaluation depends on the liver fibrosis level. Combining LSM with a blood fibrosis test improves mortality risk assessment.

Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity.

BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.

Improved fibrosis staging by elastometry and blood test in chronic hepatitis C.

AIMS: Our main objective was to improve non-invasive fibrosis staging accuracy by resolving the limits of previous methods via new test combinations. Our secondary objectives were to improve staging precision, by developing a detailed fibrosis classification, and reliability (personalized accuracy) determination. METHODS: All patients (729) included in the derivation population had chronic hepatitis C, liver biopsy, 6 blood tests and Fibroscan. Validation populations included 1584 patients. RESULTS: The most accurate combination was provided by using most markers of FibroMeter and Fibroscan results targeted for significant fibrosis, i.e. 'E-FibroMeter'. Its classification accuracy (91.7%) and precision (assessed by F difference with Metavir: 0.62 ± 0.57) were better than those of FibroMeter (84.1%, P < 0.001; 0.72 ± 0.57, P < 0.001), Fibroscan (88.2%, P = 0.011; 0.68 ± 0.57, P = 0.020), and a previous CSF-SF classification of FibroMeter + Fibroscan (86.7%, P < 0.001; 0.65 ± 0.57, P = 0.044). The accuracy for fibrosis absence (F0) was increased, e.g. from 16.0% with Fibroscan to 75.0% with E-FibroMeter (P < 0.001). Cirrhosis sensitivity was improved, e.g. E-FibroMeter: 92.7% vs. Fibroscan: 83.3%, P = 0.004. The combination improved reliability by deleting unreliable results (accuracy <50%) observed with a single test (1.2% of patients) and increasing optimal reliability (accuracy ≥85%) from 80.4% of patients with Fibroscan (accuracy: 90.9%) to 94.2% of patients with E-FibroMeter (accuracy: 92.9%), P < 0.001. The patient rate with 100% predictive values for cirrhosis by the best combination was twice (36.2%) that of the best single test (FibroMeter: 16.2%, P < 0.001). CONCLUSION: The new test combination increased: accuracy, globally and especially in patients without fibrosis, staging precision, cirrhosis prediction, and even reliability, thus offering improved fibrosis staging.

Corrigendum: Study Protocol: Randomised Controlled Trial Assessing the Efficacy of Strategies Involving Self-Sampling in Cervical Cancer Screening.

[This corrects the article DOI: 10.3389/ijph.2022.1604284.].

Acceptance of Self-Sampling by Women Not Regularly Participating in Cervical Cancer Screening in Areas with Low Medical Density: A Qualitative Study within the French CapU4 Trial.

Cervical cancer (CC) was diagnosed in 3159 women in France in 2023, and 1117 died from it. Organized screening for cervical cancer is potentially very effective for participating women. However, reaching under-screened populations remains a major challenge. The present qualitative study explored women's opinions on what discourages or encourages them to participate in CC screening and assessed the acceptability of two experimental strategies (urinary or vaginal self-sampling kits) to increase the screening coverage in three rural French administrative departments with low medical density and/or low screening participation rates. Forty-eight semi-structured interviews and four focus groups were conducted by a team of psychologists. Results showed that the participants accepted at-home self-sampling to reach non-participating women in medically underserved areas. However, they suggested that the type of kit sent should be adapted to the patient's profile (embarrassment from earlier exams, cultural aspects, fear of invasiveness, etc.), and that kits should be simple to use (in understandable language taking sociocultural aspects into account). Women wished to be assured that testing on self-samples is accurate and needed information about further actions in case of a positive result.

Acceptability to Healthcare Professionals of Home-Based HPV Self-Sampling for Cervical Screening: A French Qualitative Study Conducted in an Area with Low Access to Health Services.

Self-sampling may improve participation in cervical cancer secondary prevention programs by women who do not respond or respond irregularly when invited to contact a health professional for the collection of a cervical specimen. It could also help resolve access problems in areas with a low physician density. The present qualitative study examined barriers to screening, effective screening strategies, and the advantages and disadvantages of sending women urine or vaginal self-sampling kits in two medically underserved administrative departments in France (Mayenne and Sarthe) showing low cervical screening coverage. As part of the CapU4 randomized trial, a team of psychologists investigated the attitudes and experiences of 59 healthcare professionals (gynecologists, general practitioners, and midwives) through semi-structured interviews. Results indicated that health professionals believe that self-sampling may address the issues of low physician density and underscreening by removing logistical, organizational, financial, and psychological obstacles. They confirmed trust in the use of vaginal self-sampling, with urine self-sampling as an alternative solution (e.g., for women with vaginismus). The health professionals also identified several limitations of the self-sampling kit that will need to be addressed in future screening campaigns (incomplete kit, complex instructions, poor anatomical knowledge, and obesity).

Prevalence, risk factors, and molecular epidemiology of hepatitis B and hepatitis delta virus in pregnant women and in patients in Mauritania.

No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti-HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3 log IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV-RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub-genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV-1, 90.3% and HDV-5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country.

Acute hepatitis B in pregnancy with surprisingly rapid clearance of serum HBs antigen associated with a favourable outcome.

Acute hepatitis B (AHB) is usually asymptomatic, but it can progress to chronic hepatitis B (HB) defined by HB surface antigen (HBsAg) persisting beyond 6 months. Nevertheless, the delay of HBsAg seroclearance is not well-defined. During pregnancy, the immune system of the pregnant women is altered and delayed HBsAg loss can be observed, leading to chronic infection. Here, we present an uncommon case of AHB in a pregnant woman in whom rapid HBsAg seroclearance (52 days after AHB) was associated with a favourable outcome (no injury to liver). This patient received tenofovir disoproxil fumarate promptly after diagnosis. The case raises questions about the use of antiviral treatment in AHB. This is generally not recommended in AHB, but it would be potentially useful in pregnant women to reduce the risk of chronic HB infection and could also prevent the transmission of the maternal precore mutation, thus reducing the significant risk of fulminant hepatitis in the infant. This case also highlights the impact of the hepatitis B virus (HBV) genotype and precore/core mutations on the clinical course of the disease.

Analysis of hepatic fibrosis markers in the serum of chronic hepatitis B patients according to basal core promoter/precore mutants.

The A1762T/G1764A double mutant in the basal core promoter (BCP) region of the hepatitis B virus (HBV) is associated with severe hepatic lesions while the G1899A mutation with the double mutant is associated with a significant reduction in the risk of severe fibrosis. This study aims to measure a number of markers in the serum of patients with chronic HBV infection and to assess relationships between these markers and BCP/precore mutants with consideration of the stage of fibrosis. The serum levels of resistin, TGF-ß1, MMP-1, TIMP-1, collagen IA1 and PDGF-BB, which are markers that are known to be involved in the process of hepatic fibrosis, were assayed. The serum levels of PDGF-BB and TIMP-1, and the mutation profile were independently associated with advanced fibrosis. A higher level of TIMP-1 was associated with advanced fibrosis regardless of the mutation status, and a higher level of PDGF-BB was associated with nonsevere fibrosis in patients infected with viruses harboring the A1762T/G1764A or A1762T/G1764A/G1899A mutations. Our results suggest an impact of the A1762T/G1764A mutant on the biological pathway related to TGF-ß1 and PDGF-BB. In vitro studies are needed to understand the impact of these mutants on the serum secretion of markers involved in fibrosis severity.

Study Protocol: Randomised Controlled Trial Assessing the Efficacy of Strategies Involving Self-Sampling in Cervical Cancer Screening.

Objectives: The cervical cancer screening coverage remains moderate (60%) in France. The aim of the study is to evaluate the efficacy of two experimental invitation strategies (offer of urine or vaginal self-sampling kits) to reach under-screened populations and compare them with the current invitation strategy in rural departments (low medical density and low participation rate) in France. Methods: The study is a randomised controlled trial with three arms: a control arm (conventional invitation letter) and two experimental arms (mailing of a urine or vaginal self-sampling kit). The target population includes women aged 30-65 years, who had no screening test recorded since more than 4 years and who did not respond to an invitation letter within 12 months before. The primary outcome measure is the participation rate in each arm. A team of psychologists will also investigate attitudes and experiences by semi-structured/focus-group interviews with voluntary CapU4 participants and with health professionals. Result and conclusion: CapU4 will identify effective strategies to reach women not responding to current screening invitations and will generate information about acceptance of self-sampling among women and health professionals.

Residual risk of mother-to-child transmission of hepatitis B virus infection despite timely birth-dose vaccination in Cameroon (ANRS 12303): a single-centre, longitudinal observational study.

BACKGROUND: In sub-Saharan Africa, administration of hepatitis B virus (HBV) birth-dose vaccines remains suboptimal. Evidence is scarce on whether African countries should focus on increasing vaccine coverage or developing strategies incorporating additional measures, such as peripartum antiviral prophylaxis to pregnant women at high risk. To better inform decision makers, we estimated the residual risk of mother-to-child transmission despite HBV birth-dose vaccine in Cameroon. METHODS: We did a single-centre, longitudinal observational study. Pregnant women were systematically screened for HBV surface antigen (HBsAg) at Tokombéré District Hospital (Tokombéré district, Cameroon). Children born to HBsAg-positive mothers in 2009-16 who received the HBV birth-dose vaccine and three subsequent doses of pentavalent vaccine at 6, 10, and 14 weeks were followed up prospectively in 2015-17. In children, capillary blood was obtained for HBsAg rapid test and dried blood spots to quantify HBV DNA concentrations. Venous blood was also collected from HBsAg-positive children. Mother-to-child transmission was confirmed by whole-genome sequencing. FINDINGS: Between Jan 31, 2009, and Dec 31, 2016, 22 243 (66·8%) of 33 309 pregnant women accepted antenatal HBV screening, of whom 3901 (17·5%) were HBsAg positive. 2004 (51·4%) of 3901 children who were born to HBsAg-positive mothers received the HBV birth-dose vaccine, of whom 1800 (89·8%) also completed the three-dose pentavalent vaccine. In total, the current analysis included 607 children who had a follow-up serosurvey. The prevalence of HBsAg was 5·6% in children who received the birth-dose vaccine in less than 24 h, 7·0% in those who received it 24-47 h after birth, and 16·7% in those who received it 48-96 h after birth (ptrend=0·083). 35 (89·7%) of 39 infected children were born to mothers positive for HBV e antigen with high HBV DNA of 5·3 log10 IU/mL or more. Whole-genome sequencing of HBV in infected mother-child pairs confirmed high identity proportions of 99·97-100%. INTERPRETATION: We documented a substantial risk of mother-to-child transmission despite timely administration of the HBV birth-dose vaccine within 24 h after birth. To reach WHO's elimination targets, peripartum antiviral prophylaxis might be required in parts of Africa, in addition to increasing coverage of the HBV birth-dose vaccine. FUNDING: Agence nationale de recherches sur le sida et les hépatites virales (ANRS).