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.].

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).

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.

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.

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).

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.

Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals.

SARS-CoV-2 coronavirus infection induces heterogeneous symptoms, ranging from asymptomatic to lethal forms. Severe forms usually occur in the elderly and/or individuals with comorbidities. Children generally remain asymptomatic to primary infection, suggesting that they may have an effective local innate immune response. IFN-I and -III have non-redundant protective roles against SARS-CoV-2, although sometimes damaging the host. The expression and role of anti-viral peptides during SARS-CoV-2 infection have thus far been little studied. We aimed to identify the innate immune molecules present at the SARS-CoV-2 entry point. We analyzed the mRNA levels of type I (IFN-α and -ß) and type III (IFN-λ1-3) interferons and selected antiviral peptides (i.e., ß-defensins 1-3, α-defensins [HNP1-3, HD5] pentraxin-3, surfactant protein D, the cathelicidin LL-37 and interleukin-26) in nasopharyngeal swabs from 226 individuals of various ages, either infected with SARS-CoV-2 (symptomatic or asymptomatic) or negative for the virus. We observed that infection induced selective upregulation of IFN-λ1 expression in pediatric subjects (≤15 years), whereas IFN-α, IFN-ß, IFN-λ2/λ3, and ß-defensin 1-3 expression was unaffected. Conversely, infection triggered upregulation of IFN-α, IFN-ß, IFN-λ2/λ3, and ß-defensin 1-3 mRNA expression in adults (15-65 years) and the elderly (≥ 65 years), but without modulation of IFN-λ1. The expression of these innate molecules was not associated with gender or symptoms. Expression of the interferon-stimulated genes IFITM1 and IFITM3 was upregulated in SARS-CoV-2-positive subjects and reached similar levels in the three age groups. Finally, age-related differences in nasopharyngeal innate immunity were also observed in SARS-CoV-2-negative subjects. This study shows that the expression patterns of IFN-I/-III and certain anti-viral molecules in the nasopharyngeal mucosa of SARS-CoV-2-infected subjects differ with age and suggests that susceptibility to SARS-CoV-2 may be related to intrinsic differences in the nature of mucosal anti-viral innate immunity.

From national HBV and HDV screenings to vaccination and treatment in healthcare workers: The Mauritanian pilot study.

OBJECTIVES: Hepatitis B and D infections are highly endemic in Mauritania, with prevalences ranging from 10 to 20%. With the present prospective transversal pilot study, we aimed to evaluate the prevalences of HBV, HCV, and HDV infections in healthcare workers (HCWs), and offer treatment or vaccination as required. METHODS: At inclusion, each HCW was screened for anti-HBc Ab (followed by HBsAg assay when positive). Additional biological analyses were performed for HBsAg + cases. Depending on the results, HBV vaccination or anti-viral treatment was offered. RESULTS: A total of 3,857 HCWs were included, of whom 1,363 tested negative for anti-HBc Ab and received full vaccination. Of the 2,494 HCWs who were positive for anti-HBc Ab, 1,246 were positive for anti-HBs Ab and 418 were positive for HBsAg. Three HCWs were positive for HBeAg; 66 and 18 had HBV DNA levels respectively > 2,000 and > 20,000 IU/mL; and 48 were positive for anti-HDV Ab among whom 10 were positive for HDV RNA. HCV prevalence was 0.5%. Only seven HCWs fulfilled the criteria for treatment and five of them were treated. CONCLUSION: Few HCWs in Mauritania are immunised against HBV. The prevalences of anti-HBc Ab and HBsAg observed in this work were similar to those observed in our earlier works, whereas prevalence of active HDV infection was less high. HBV and HDV infections are a serious health concern in Mauritania. New recommendations developed in accordance with WHO guidelines should include mandatory HBV screening and immunisation for HCWs.

Evaluation of the Aptima™ HBV Quant Dx assay for semi-quantitative HBV viral load from dried blood spots.

BACKGROUND: The detection and quantification of hepatitis B virus (HBV) DNA from dried blood spots (DBS) is a major tool for chronic hepatitis B management in resource-limited settings. This strategy fits in perfectly with the hepatitis control plan promoted by the World Health Organization. However, few commercial methods are validated for viral load (VL) measurement on DBS. OBJECTIVES: Our objective was to evaluate the performance of the HBV VL measurement of the Aptima™ HBV Quant Dx assay on DBS compared to plasma samples on the Panther® platform (Hologic). STUDY DESIGN: 266 whole blood samples for routine measurement were included. Five spots of 75 µL of whole blood were loaded onto a card before centrifugation and plasma settling. RESULTS: 149 samples were quantifiable and 117 were not detected. We achieved excellent linearity (r²â€¯= 0.994) over a wide range of measurements suitable for clinical practice, and a 95 % lower limit of detection (LLOD-95 %) at 2.65 log10 IU/mL (445 IU/mL). A good performance of this assay was observed for samples with HBV VL > LLOD-95 % and 100 % of samples were detected if HBV VL was above 2.95 log10 IU/mL. The correlation between the two matrices for quantitative VLs was good (r²â€¯= 0.978) with a very low bias (-0.002 log10 IU/mL). CONCLUSION: The Aptima™ assay can properly detect and quantify HBV DNA in DBS, providing a satisfactory use in clinical monitoring and therapeutic decisions. DBS represents an excellent alternative to plasma, especially in resource-limited countries, while maintaining the performance and advantages of an automated technique.

Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: Two automated immunoassays (Euroimmun and Abbott) and one rapid lateral flow immunoassay (NG Biotech).

BACKGROUND: The emergence of new SARS-CoV-2 has promoted the development of new serological tests that could be complementary to RT-PCR. Nevertheless, the assessment of clinical performances of available tests is urgently required as their use has just been initiated for diagnose. OBJECTIVES: The aim of this study was to assess the performance of three immunoassays for the detection of SARS-CoV-2 antibodies. METHODS: Two automated immunoassays (Abbott SARS-CoV-2 CLIA IgG and Euroimmun Anti-SARS-CoV-2 ELISA IgG/IgA assays) and one lateral flow immunoassay (LFIA NG-Test® IgG-IgM COVID-19) were tested. 293 specimens were analyzed from patients with a positive RT-PCR response, from patients with symptoms consistent with COVID-19 but exhibiting a negative response to the RT-PCR detection test, and from control group specimens. Days since symptoms onset were collected from clinical information sheet associated with respiratory tract samples. RESULTS: Overall sensitivity for IgG was equivalent (around 80 %) for CLIA, ELISA and LFIA. Sensitivity for IgG detection, >14 days after onset of symptoms, was 100.0 % for all assays. Overall specificity for IgG was greater for CLIA and LFIA (more than 98 %) compared to ELISA (95.8 %). Specificity was significantly different between IgA ELISA (78.9 %) and IgM LFIA (95.8 %) (p < 0.05). The best agreement was observed between CLIA and LFIA assays (97 %; k = 0.936). CONCLUSION: Excellent sensitivity for IgG detection was obtained >14 days after onset of symptoms for all immunoassays. Specificity was also excellent for IgG CLIA and IgG LFIA. Our study shows that NG-Test® is reliable and accurate for routine use in clinical laboratories.

Urinary HPV DNA testing as a tool for cervical cancer screening in women who are reluctant to have a Pap smear in France.

OBJECTIVES: In France, cervical cancer screening is based on human papillomavirus (HPV) testing on cervical samples (women aged 30-65) and cytological examination of Pap smears (25-29), but screening coverage is unsatisfactory. The CapU3 study aimed to propose urinary HPV testing on 13,535 women aged 35 to 65 who had not had a Pap smear since 2010. METHODS: High-risk HPV (HR-HPV) detection was performed using a real-time PCR (Anyplex II HPV 28 Detection, Seegene®). Women with HR-HPV positive results were encouraged to have a cervical smear as soon as possible to detect the presence of cervical lesions. RESULTS: The participation rate was 15.4%. Out of the 1,915 analyzed specimens, 1,711 and 190 were negative and positive, respectively, for at least 1 HR-HPV genotype. HR-HPV genotypes other than HPV-16 or HPV-18 were mostly detected as HPV-53 (23.7%) and HPV-68 (14.2%). A satisfactory gynecological follow-up was observed for HPV-positive women (92.1%). 23 abnormal smears were observed and eight high-grade cytological lesions after colposcopy and biopsy were diagnosed. CONCLUSIONS: As home HPV urinary testing is non-invasive and does not require medical attention, this method may be an alternative for women who are reluctant to have a Pap smear and thus extend screening coverage.

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 first experience of transduction for differentiated HepaRG cells using lentiviral technology.

Currently, there is a lack of systems for studying the role of hepatitis B viral proteins, such as HBeAg and HBcAg, on liver injury. It is necessary to develop an original tool in order to clarify the role of these viral proteins in hepatic stellate cell activation, and to understand the molecular mechanisms of liver injury. HepaRG are the most reliable hepatocyte-like cells for studying liver functions or disorders. In this paper, we demonstrate that the transduction of differentiated HepaRG (dHepaRG) cells can be performed successfully using lentiviral particles. The production of a functional Green Fluorescent Protein (GFP) assessed by Fluorescence Activated Cell Sorting and fluorescence microscopy is up to 16% of GFP positive cells using a multiplicity of infection (MOI) of 2.4. We demonstrate that this technology can allow the stable expression of GFP during the long lifecycle of the cell (up to four weeks after the cell's passage). With this innovative tool, we aim to express viral proteins such as HBeAg or HBcAg in dHepaRG cells. The preliminary results of this work shows that HBeAg can be efficiently produced in dHepaRG cells and that increased MOI allows a better production of this protein. Our future objective will be to study the role of HBc and HBe proteins on the induction of hepatic fibrosis.

Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma.

BACKGROUND: The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies. METHODS: Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event. RESULTS: Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients. CONCLUSIONS: These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases.

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.

Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin.

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of <1 log IU/ml during the pegIFN-RBV lead-in phase). The impact of the presence of these RAVs on the outcome of triple therapy was studied. Among 282 patients, the prevalances (95% confidence intervals) of baseline RAVs ranged from 5.7% (3.3% to 9.0%) to 22.0% (17.3% to 27.3%), depending to the algorithm used. Among mutations conferring a >3-fold shift in 50% inhibitory concentration (IC50) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (P = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.

Home-based urinary HPV DNA testing in women who do not attend cervical cancer screening clinics.

In France, cervical cancer screening is currently based on cytological examination of a Pap smear for women aged 25 to 65, but screening coverage is unsatisfactory. Previous studies have shown that self-sampling for human papillomavirus (HPV) testing increases rates of compliance. With this purpose in mind, we performed the CapU study to evaluate the acceptance of a urinary HPV test. Letters proposing a new cervical cancer screening method using at-home urine self-sampling were sent to 5000 women aged 40-65 years who had not had a Pap smear over the past three years. The participating patients had to send their urine samples to the Angers Hospital Virology Laboratory for analysis using real-time PCR. Of the 771 samples received, 687 were analyzed. High-risk HPV were detected in 29 women. In follow-up, 28 women with positive urinary HPV results had a Pap smear or colposcopy done. The cytological results showed nine abnormal Pap smears, among which histology studies confirmed three cases of cervical intraepithelial neoplasia grade III lesions. Our study shows that urinary HPV testing may be pertinent to women who do not have cervical Pap smears done and lead to the diagnosis of high-grade cervical lesions.

High endemicity and low molecular diversity of hepatitis B virus infections in pregnant women in a rural district of North Cameroon.

BACKGROUND: A program, supported by the GEMHEP (Groupe d'étude Moléculaire des Hépatites), was established in 2007 in the sanitary district of Tokombéré, to prevent perinatal transmission of hepatitis B virus (HBV). It comprises screening for HBV surface antigen (HBsAg) in all pregnant women and vaccinating the newborn if tests are positive. METHODS/PRINCIPAL FINDINGS: 1276 women were enrolled in the study after providing informed consent. Demographic data and blood samples were available for 1267 of the enrolled patients. HBsAg was determined locally using a rapid test (Vikia HBsAg, Biomerieux). Tests for HBV and HDV virological markers (HBeAg, anti-HDV antibodies (Ab), HBV-DNA, HDV-RNA, HBV and HDV genotypes) were performed on the confirmed HBsAg-positive samples in the virology unit of the Angers University Hospital (France). HBsAg was found in 259 of the 1267 pregnant women (20.4%) between January 2009 and April 2010, of whom 59 were HBeAg-positive (22.7%) with high levels of HBV-DNA. Anti-HDV Ab were found in 19 (7.3%) of the HBsAg-positive women. The prevalence rates of HBsAg and HDV were not age-dependent whereas HBeAg carriers were statistically younger than non carriers. Basal core promoter (BCP) and precore (PC) mutations and genotypes were determined by sequencing. Of 120 amplified sequences, 119 belonged to HBV genotype E (HBV/E) and the 9 HDV strains belonged to HDV clade 1. In the PC region, 83/228 patients (36.4%) harbored a G1896A mutant or mixed phenotype virus. In the BCP region, the double mutation A1762T/G1764A and the G1757A substitution were detected respectively in 26/228 patients (11.4%) and 189/228 patients (82.8%). CONCLUSIONS: Our results confirm the high prevalence and low molecular diversity of HBV in Far Northern Cameroon; more than 20% of the infected women were highly viremic, suggesting a high rate of HBV perinatal transmission and supporting the WHO recommendation to vaccinate at birth against hepatitis B.