New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection. METHODS: This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score. RESULTS: In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases. CONCLUSION: Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Positive predictive value of seroconversion or positive rubella IgM in diagnosis of maternal rubella infection: Seven-years review of French National Reference Laboratory for Rubella.

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 %).

Determination of rubella virus-specific humoral and cell-mediated immunity in pregnant women with negative or equivocal rubella-specific IgG in routine screening.

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.

Cytomegalovirus non-primary infection during pregnancy. Can serology help with diagnosis?

Diagnosis of cytomegalovirus (CMV) primary infection is reliable, but diagnosis of CMV non-primary infection (NPI) is questionable. Our aim is to highlight the difficulties met in diagnosis of CMV NPI. We illustrate that in proven cases of CMV NPI, very different serologic and molecular patterns may be observed and that routine serologic testing may fail to help with diagnosis. These results point out that many data available in literature concerning the prevalence of NPI, materno-fetal transmission rates and consequences of NPI may be wrong. We need to know how frequently they occur, are transmitted and cause fetal damages. Diagnosis of NPI must be improved, along with our understanding of the mechanisms leading to intrauterine CMV transmission and congenital infection in babies born to women with preexisting immunity.

Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients.

BACKGROUND: The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. OBJECTIVES: In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. STUDY DESIGN: We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. RESULTS: We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e(-5), thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). CONCLUSIONS: We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis.