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Aims / background Rubella virus-associated uveitis (RVAU) classically presents with the clinical features of Fuchs uveitis syndrome (FUS). We report a series RVAU, and discuss the relevance of available diagnostic strategies, and how vaccination could potentially prevent disease. Methods We retrospectively included patients with RV-positive aqueous humor (AH) with RT-PCR and/or intraocular RV-IgG production, between January 2014 and December 2019. RV-IgG titers from AH and serum were compared with other virus-specific IgG titers (VZV and/or CMV and/or HSV-1), to determine the derived Goldmann-Witmer coefficient (GWC’). Clinical findings at presentation and during follow-up are reported, as well as the anti-RV vaccination status. Results All 13 included patients demonstrated intraocular synthesis of RV-IgG (median GWC’: 9.5; 3.2–100). RV-RNA was detected in one patient while PCR results were negative for other HSV1, VZV and CMV. The mean delay in diagnosis was 13 ± 12.6 years, with an initial presentation of FUS in only 3 patients (23%). Only four patients had been vaccinated, but all after the recommended age. Conclusion As RVAU is a pleiomorphic entity, virological analysis (RV RT-PCR and GWC’) of aqueous humor is essential to improve the diagnosis and management of this entity. Improper vaccination against RV appears to be implicated in RVAU.

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 14-year-old patient underwent liver transplant. Three months after transplantation, EBV associated lymphoma was suspected. EBV serologies before and after transplantation were particularly discrepant. Eighteen months before transplantation, the serological profile suggested a recent EBV primary-infection, four months before transplantation, we had isolated anti-EBNA IgG and five days after transplantation, the serological profile suggested a past infection. All EBV PCR performed on whole blood were negative. Retrospectively, immunoblots anti-EBV IgG were performed. Blots showed no anti-EBV IgG before and until the day of liver transplantation. Five days after transplantation, slight bands of both IgG anti-p18 (VCA) and anti-EBNA-1 were found, without any other serological marker. These were probably due to passive transfers of IgG during surgery. There was therefore no argument for an immunization against EBV before or after liver transplant for this patient.Un patient de 14 ans a subi une transplantation hépatique. Trois mois après la transplantation, un lymphome associé à l’EBV a été suspecté. Les sérologies anti-EBV (IgG anti-VCA et anti-EBNA, IgM anti-VCA) montraient des résultats particulièrement discordants et ininterprétables : profil de primo-infection EBV récente 18 mois avant la greffe, IgG anti-EBNA isolées 4 mois avant la greffe et profil d’infection ancienne 5 jours après la greffe. Les PCR EBV réalisées sur sang total étaient toujours indétectables. Rétrospectivement, des immunoblots IgG anti-EBV ont été réalisés. Les blots ne montraient pas d’IgG anti-EBV en pré-greffe jusqu’au jour de la transplantation. Cinq jours après la greffe, le blot montrait la présence d’anti-p18 (VCA) et anti-EBNA-1 présents sous forme de traces, sans autre marqueur sérologique d’infection EBV, très probablement dues à des transferts passifs d’anticorps pendant la transplantation. Aucun argument sérologique ni moléculaire n’a été retenu pour une immunisation anti-EBV avant ou après la transplantation hépatique pour ce patient.

Background: Immunity to rubella-virus (RV) is commonly determined by measuring specific IgG (RV-IgG). However, RV-IgG results may be different and even discordant, depending on the assay used. Cell-mediated immunity is not routinely investigated for diagnostic purposes. Objectives: Our aim was to investigate humoral and cellular immunity of women with negative or equivocal RV-IgG before, and after post-partum vaccination. Study design: A total of 186 pregnant women were included in the study. During pregnancy, humoral immunity was investigated with two RV-IgG immunoassays, an immunoblot and a T-cell mediated immunity test. In the post-partum vaccination period, measuring RV-IgM and RV-IgG avidity allowed us to determine whether women raised a primary or a secondary immune response. Results: Before vaccination, 52.2% women, supposed to be susceptible, had positive anti-E1 RV-IgG indicating strong evidence of previous exposure to RV. All (100%) pregant women who had a positive immunoblot before immunization raised a secondary immune response to vaccination, and 96.8% who had a negative immunoblot before immunization, raised a primary immune response to vaccination. All women who raised a primary immune response after vaccination had negative anti-E1 RV-IgG and negative cell-mediated immunity. Discussion: These results indicate that individuals can have evidence of protective immunity against rubella despite negative RV-IgG.

International audience; Background: Diagnosis of Cytomegalovirus (CMV) primary infection during pregnancy or in immunocompetent patients relies on serology with detection of specific CMV-IgG and IgM. In case of positive CMV-IgM in pregnant women, CMV-IgG avidity is now widely recommended, but in general population it is not currently performed.Objective: In this study, we aimed to determine CMV-IgM positive predictive values (PPV) in different clinical settings.Material and methods: We conducted a retrospective study on positive CMV-IgM in our virology laboratory from 2013 to 2019, in three clinical groups: screening in non-symptomatic pregnant women (group 1), pregnant women with ultrasound (US) abnormalities (group 2) and patients (general population) with clinical signs suggestive of CMV primary infection (group 3). CMV-IgG avidity had been performed in all cases allowing to evaluate PPV of positive CMV-IgM to diagnose CMV primary-infection in each group.Results: Between 2013 and 2019, 6859 serum samples were found positive for CMV-IgM and had been tested for CMV-IgG avidity, with 6560 sera for group 1, 30 for group 2 and 269 for group 3. Overall, low avidity confirming primary infection was observed respectively in 16.4 % for group 1, 36.7 % for group 2, and 35.3 % for group 3. CMV-IgM PPV was significantly lower in group 1 compared to groups 2 (p = 0.01) and 3 (p < 0.001).Discussion: Our observations highlight the major importance of including CMV-IgG avidity in the diagnostic algorithm, whatever the clinical situation (for immunocompetent patients), to confirm or exclude a recent CMV primary infection in case of positive CMV-IgM.

International audience; Background: Co-infections may represent substantial diagnostic and treatment challenges. Aim: To the better of our knowledge, we describe the first case in the literature of congenital Cytomegalovirus (CMV) infection following maternal CMV non primary infection contemporary to varicella during pregnancy. Case Presentation: A pregnant woman had a varicella during her pregnancy. Congenital CMV infection was fortuitously discovered in the neonate owing to a universal CMV screening. Retrospective analysis of maternal serums during pregnancy showed CMV reactivation. We aim to highlight that CMV reactivation could be due to varicella and discuss if it could facilitate the transplacental transmission of CMV. Conclusion: This case report emphasizes neonatal CMV screening, and warns against dual maternal infection especially because this may be at particular risk of transmission to the fetus.

International audience; no abstract

Immunity to rubella virus (RV) is commonly determined by measuring specific immunoglobulin G (RV IgG). However, RV IgG results and their interpretation may vary, depending on the immunoassay, even though most commercial immunoassays (CIAs) have been calibrated against an international standard and results are reported in international units per milliliter. A panel of 322 sera collected from pregnant women that tested negative or equivocal for RV IgG in a prior test (routine screening) was selected. This panel was tested with two reference tests, immunoblotting (IB) and neutralization (Nt), and with 8 CIAs widely used in Europe. IB and Nt gave concordant results on 267/322 (82.9%) sera. Of these, 85 (26.4%) sera were negative and 182 (56.5%) sera were positive for both tests. All 85 IB/Nt-negative samples were classified as negative with all CIAs. Of the 182 IB/Nt-positive samples, 25.3 to 61.5% were classified as equivocal and 6 to 64.8% were classified as positive with the CIAs. Wide variations in titers in international units per milliliter were observed. In our series, more than half of the women considered susceptible to RV based on CIA results tested positive for RV antibodies by IB/Nt. Our data suggest that (i) sensitivity of CIAs could be increased by considering equivocal results as positive and (ii) the definition of immunity to RV as the 10-IU/ml usual cutoff as well as the use of quantitative results for clinical decisions may warrant reconsideration. A better standardization of CIAs for RV IgG determination is needed.

Background In France, as in most developed countries, childbearing age women are routinely screened for rubella antibodies to identify and vaccinate susceptible women. Immunity to rubella is usually determined by measuring the rubella virus-specific immunoglobulin G (RV-IgG). In case of seroconversion for RV-IgG and/or positive RVIgM during pregnancy, laboratories usually send serum samples to the French National Reference Laboratory (FNRL) for Rubella in order to perform complementary investigations and confirm or exclude rubella infection during pregnancy. Objective Our aim is to report results of these investigations during a seven-year period (2013–2019) and evaluate the positive predictive value (PPV) of RV-IgG seroconversion or positive RV-IgM to diagnose maternal rubella infection in France. Study design Between 2013 and 2019, 5398 serum samples collected from 4104 pregnant women, were addressed to FNRL because of RV-IgG seroconversion (N=899) or positive RV-IgM (N=3205). Additional serological tests were performed, mainly immunoblot (to look for the presence of anti-E1 protective antibody) and RV-IgG avidity (to exclude or confirm primary infection). Results Overall, for 3724/4104 (90.8 %) women, rubella primary-infection during pregnancy was formally excluded and maternal rubella primary-infection was only confirmed in 46/4104 (1.1 %) cases. Conclusion Clinicians and biologists should be particularly aware that RV-IgG seroconversion or positive RV-IgM, in the current context of low RV circulation in France are most often not rubella primary infections. PPV of seroconversion to assess maternal rubella primary infection is as low as 0.2 % (95 % CI: 0 %; 0.5 %) and PPV of positive RV-IgM is only of 1.4 % (95 % CI: 0.99 %; 1.81 %).

Background ZIKV infection has potentially severe consequences particularly in fetuses/newborns born to mothers that were infected early in pregnancy. Diagnosis relies on the detection of ZIKV IgM that can also be detected due to cross reactivity or to nonspecific polyclonal activation of the immune system. Therefore, in case of ZIKV IgM detection, identification of a recent infection can be of major importance for the optimal management of pregnant women. Objective This study evaluates the performances of a commercially available assay to measure ZIKV-IgG avidity. Study design A total of 110 serum or plasma samples collected from symptomatic or asymptomatic patients living or returning from a ZIKV endemic area were classified according to epidemiological and clinical information, and to serology and molecular assays’ results. Samples were tested with the IgG ZIKV Avidity Test (DIA.PRO®) according to manufacturer’s instruction and with a modified protocol. Results By using the manufacturer’s Avidity Index cut-off, distinction between recent and past infection was unclear with similar AIs in the two situations (p = 0.8872). Sensitivity and specificity in identifying recent infection were poor, 67.3 % and 4.5 % respectively. By using a modified protocol, a better discrimination was observed with significant differences between mean AIs (p = 0.0318), and with higher sensitivity and specificity, respectively 87.8 % and 100 %. Conclusion Our results highlight that IgG ZIKV Avidity Test DIA.PRO® assay is not reliable enough to be used in clinical practice without modifications.

Prevention is an essential aspect of management of infections that can be transmitted from mother to fetus during pregnancy: The prescription and interpretation of serologic markers differ according to clinical context: screening, counts, clinical signs, or ultrasound signs. Testing for rubella IgG antibodies is recommended at the beginning of pregnancy, in the absence of written results proving either immunity or previous vaccination with two doses. Monthly serologic monitoring (IgG and IgM) is recommended for woman lacking immunity to toxoplasmosis. Diagnosis of a primary infection requires the concomitant detection of IgG and IgM. Nonetheless, the presence of specific IgM is not necessarily a marker of recent infection. IgG avidity must be measured to confirm or rule out a recent primary infection when IgM is positive. The observation of stable antibody titers is often inaccurately considered to be reassuring. In fact, depending on the individuals tested and especially the technique used, antibodies may reach a plateau several days or several weeks after the onset of the infection. Clinical diagnosis of rubella is not reliable, and its rarity today means that physicians are unlikely to recognize it or consider it as a possible differential diagnosis. Nonetheless, residual circulation of the rubella virus continues in France. A chickenpox rash is diagnosed clinically. For atypical eruptions, the virus can be sought directly in the vesicular fluid. Serology is not helpful in this case.

Rubella is a mild viral disease that typically occurs in childhood. Rubella infection during pregnancy causes congenital rubella syndrome, including the classic triad of cataracts, cardiac abnormalities and sensorineural deafness. Highly effective vaccines have been developed since 1969, and vaccination campaigns have been established in many countries. Although there has been progress, the prevention and diagnosis of rubella remain problematic. This article reviews the implications and management of rubella during pregnancy.

Sporadic cases of rubella infection are reported each year in France due to insufficient vaccination coverage. Rubella virus is a very unstable enveloped RNA virus. For this reason, transportation and storage of samples collected for its detection require particular conditions. The genetic stability of rubella virus has allowed the development of very effective vaccines. During the recent rubella outbreaks in Algeria and Tunisia, an unusual high rate of encephalitis was reported. The role of the laboratory is crucial in the management of rubella infection during pregnancy. Rubella serological results must be interpreted with caution. Congenital rubella is a severe disease that should already be eliminated thanks to a very effective vaccine that has been developed. All women of childbearing age should be vaccinated. Rubella vaccination of an unknowingly pregnant woman is not an indication for abortion.

Prevention is an essential aspect of management of infections that can be transmitted from mother to fetus during pregnancy: The prescription and interpretation of serologic markers differ according to clinical context: screening, counts, clinical signs, or ultrasound signs. Testing for rubella IgG antibodies is recommended at the beginning of pregnancy, in the absence of written results proving either immunity or previous vaccination with two doses. Monthly serologic monitoring (IgG and IgM) is recommended for woman lacking immunity to toxoplasmosis. Diagnosis of a primary infection requires the concomitant detection of IgG and IgM. Nonetheless, the presence of specific IgM is not necessarily a marker of recent infection. IgG avidity must be measured to confirm or rule out a recent primary infection when IgM is positive. The observation of stable antibody titers is often inaccurately considered to be reassuring. In fact, depending on the individuals tested and especially the technique used, antibodies may reach a plateau several days or several weeks after the onset of the infection. Clinical diagnosis of rubella is not reliable, and its rarity today means that physicians are unlikely to recognize it or consider it as a possible differential diagnosis. Nonetheless, residual circulation of the rubella virus continues in France. A chickenpox rash is diagnosed clinically. For atypical eruptions, the virus can be sought directly in the vesicular fluid. Serology is not helpful in this case.

Rubella is a mild viral disease that typically occurs in childhood. Rubella infection during pregnancy causes congenital rubella syndrome, including the classic triad of cataracts, cardiac abnormalities and sensorineural deafness. Highly effective vaccines have been developed since 1969, and vaccination campaigns have been established in many countries. Although there has been progress, the prevention and diagnosis of rubella remain problematic. This article reviews the implications and management of rubella during pregnancy.

Some infections are considered as feared risks during pregnancy. These infections may lead to severe damage of the fetus or the newborn depending on the infectious agent and the term of pregnancy where the infection occurred. Antenatal screening (in France it concerns toxoplasmosis, rubella, syphilis and hepatitis B) play an important role in prevention and management of vertically transmissible infections. However, biological diagnosis is also essential when maternal/neo-natal clinical symptoms or abnormal ultrasound findings are observed. In this article we chose to focus on rubella, varicella, syphilis, toxoplasmosis, hepatitis B and cytomegalovirus and parvovirus infections.

Sporadic cases of rubella infection are reported each year in France due to insufficient vaccination coverage. Rubella virus is a very unstable enveloped RNA virus. For this reason, transportation and storage of samples collected for its detection require particular conditions. The genetic stability of rubella virus has allowed the development of very effective vaccines. During the recent rubella outbreaks in Algeria and Tunisia, an unusual high rate of encephalitis was reported. The role of the laboratory is crucial in the management of rubella infection during pregnancy. Rubella serological results must be interpreted with caution. Congenital rubella is a severe disease that should already be eliminated thanks to a very effective vaccine that has been developed. All women of childbearing age should be vaccinated. Rubella vaccination of an unknowingly pregnant woman is not an indication for abortion.

We report here three cases of trichinellosis due to polar bear meat consumption in East Greenland. In the past 20 years, 31 cases of trichinellosis have been reported in French travellers to the Arctic (North Quebec, Nunavut and Greenland) who consumed undercooked meat from black, brown, or polar bears. If local communities are increasingly becoming aware of the risk of trichinellosis, travellers visiting regions where bear meat is consumed should be informed of the risk of eating raw or non-heat-processed meats.