Measles and rubella seroprevalence in a population of young adult blood donors, France 2013.

As part of the evaluation of the French plan for the elimination of measles and rubella, we conducted a seroprevalence survey in 2013, aimed at updating seroprevalence data for people 18-32 years old. A secondary objective was to estimate measles incidence in this population during the 2009-2011 outbreak, and thus estimate the exhaustiveness of measles mandatory reporting. We used a cross-sectional survey design, targeting blood donors 18-32 years old, living in France since 2009, who came to give blood in a blood collecting site. We included 4647 people in metropolitan France, 806 people in Réunion Island and 496 in the French Caribbean. A further 3942 individuals were interviewed in the south-east region of metropolitan France to estimate the exhaustiveness of measles mandatory reporting. One of the main findings of this survey is that the proportion of people 18-32 years old susceptible to both measles and rubella infections remained high in France in 2013, 9.2% and 5.4%, respectively, in metropolitan France, even after the promotion campaigns about vaccination catch-up during and following the major measles epidemic in 2009-2011. Applying our results to French census data would suggest that around 1 million people aged 18-32 years old are currently susceptible to measles in France, despite this age group being one of the vaccination targets of the national measles elimination plan. Another important finding is that only an estimated 45% of the true number of cases in this age group was actually notified, despite notification being mandatory.

Seroprevalence of cytomegalovirus infection in France in 2010.

Cytomegalovirus (CMV) infection remains the leading cause of congenital virus infection in developed countries. Measuring the national prevalence of this infection, especially among women of childbearing age, is of great value to estimate the risk of congenital CMV infection, as well as to identify risk groups that should be targeted for behavioural interventions and/or vaccination once a CMV vaccine finally becomes available. In order to fulfil these objectives, a seroprevalence survey was conducted in 2010, using a nationally representative, population-based sample of 2536 people aged between 15 and 49 years, living in metropolitan France and attending private microbiological laboratories for blood testing. All blood samples were analysed in the same laboratory and screened for CMV-specific IgG using an enzyme-linked immunoassay technique (Elisa PKS Medac Enzyme immunoassay). The overall point estimate of CMV infection seroprevalence for individuals aged 15-49 years was 41.9%. The estimates were higher in women than in men (respectively 45.6% and 39.3%), and people born in a non-Western country were more likely to be CMV seropositive than those born in France or in another Western country (93.7% vs. 37.7%). Our results showed that a substantial percentage of women of childbearing age in France are CMV seronegative and therefore at risk of primary CMV infection during pregnancy. Educational measures and future vaccine are key issues to prevent infection in pregnant women and congenital CMV disease.

Measles outbreak in a refugee settlement in Calais, France: January to February 2016.

We report a measles outbreak in a refugee settlement in Calais, France, between 5 January and 11 February 2016. In total, 13 confirmed measles cases were identified among migrants, healthcare workers in hospital and volunteers working on site. A large scale vaccination campaign was carried out in the settlement within two weeks of outbreak notification. In total, 60% of the estimated target population of 3,500 refugees was vaccinated during the week-long campaign.

Four cases of fetal intra-abdominal umbilical vein varix: a single centre's approach to management.

Fetal intra-abdominal umbilical vein (FIUV) varix is a rare prenatal abnormality characterised by a focal intrahepatic or extrahepatic dilatation of the intra-abdominal portion of the umbilical vein. Usually, it is an isolated finding, but in some cases it can be associated to other fetal anomalies. Thrombosis is a possible complication of FIUV varix and it can lead to poor fetal or neonatal outcome. We describe four consecutive cases of FIUV varix diagnosed in our Unit and managed with low-dose aspirin (LDA) prophylaxis until the 35th week of gestation. None of the fetuses developed thrombosis of the varix and the neonatal outcomes were good in all the cases.

Spotlight on measles 2010: update on the ongoing measles outbreak in France, 2008-2010.

Since early 2008, France has been experiencing a measles outbreak with almost 5,000 notified cases as of 30 June 2010, including three measles-related deaths. The proportion of cases 20 years or older reached 38% during the first half of 2010. This situation is the consequence of insufficient vaccine coverage (90% at age 24 months in 2007) that led to the accumulation of susceptibles over the last years. It underlines the need for additional measures targeting susceptible children and young adults.

Are vaccinated measles cases protected against severe disease?

OBJECTIVES: We aimed to estimate vaccine effectiveness against severe measles based on the number of vaccine doses administered and the time since last vaccination. PATIENTS AND METHODS: We included measles cases aged at least 2 years and born since 1980 who were notified in France between 2006 and mid-2019. We considered two severity levels (moderate, severe) and calculated adjusted relative risks (aRR) using multinomial logistic regression. RESULTS: We included 10,399 cases. The risk of severe measles in two-dose vaccine recipients was 71% (aRR = 0.29 [95%CI 0.12-0.72]) and 83% (aRR = 0.17 [95%CI 0.04-0.70]) lower than in unvaccinated cases, if the time since last dose was less or more than 15 years, respectively. The risk of moderate disease followed a similar pattern. CONCLUSIONS: Two-dose measles vaccination provided long-term protection against severe cases, even after vaccine failures. These findings underscore the need for compliance to the recommended measles vaccination schedule to prevent severe cases.

Cluster of serogroup W invasive meningococcal disease in a university campus.

INTRODUCTION: In France, the expansion of an hypervirulent strain causing serogroup W invasive meningococcal disease (MenW) has been observed since 2015/16. We describe a cluster of three MenW cases, causing two deaths, at the end of 2016 in a university campus, and the vaccination campaign which was consequently organized. METHODS: Epidemiological and microbiological analyses led a multidisciplinary expertise group to recommend the organization of a mass vaccination campaign using ACWY vaccine targeting more than 30,000 students and staff in the university campus. Individual data on vaccination was collected using the lists of students and staff registered at the university to estimate vaccine coverage. RESULTS: Three MenW cases occurred within a 2-month period among students in different academic courses. All three isolates were identical and belonged to the "UK-2013 strain" phylogenetic branch. The attack rate was 10.8/100,000 students. The vaccination campaign was organized only 15 days after the third case occurred. In total, 13,198 persons were vaccinated. Vaccine coverage was estimated at 41% for students of the university and 35% for university staff. CONCLUSION: Timely notification of cases to health authorities was essential for the detection of the cluster and the rapid implementation of the vaccination campaign. No further cases occurred in the campus in the year following the vaccination campaign. This episode is the second cluster of MenW caused by the "UK-2013 strain" in a university since 2016.

Measles resurgence in France in 2008, a preliminary report.

Since the beginning of 2008, France is experiencing a resurgence of measles. It started in a religious traditionalist group with low coverage and secondarily spread to the general population. This situation is the consequence of the insufficient vaccine coverage (less than 90 % at 24 months of age) which had led to the accumulation of susceptibles over the last years. More than 550 cases have been notified in 2008, the vast majority being unvaccinated. One measles-related death has occurred early 2009. Efforts to enhance communication to the general public and the health professionals on measles vaccination and control measures around cases are ongoing.

Prevalence of hepatitis C and hepatitis B infection in the HIV-infected population of France, 2004.

Our objective was to estimate the prevalence of HCV and HBV co-infection among HIV-infected adults in France and describe the epidemiological characteristics of co-infected patients and their clinical management. A one-day national cross-sectional survey was conducted in 2004. A random and proportional probability sample design was used, based on the number of AIDS cases reported since 1999 by hospital wards. Weighted estimations were computed. HIV-infected adults (out/in-patients) were included after consent. Data were collected on demographic criteria, HIV, HCV and HBV infections, as well as on antiviral therapies. Overall, 1849 HIV-infected patients were included. The prevalence of anti-HCV or HCV RNA positivity (HCV co-infection) was 24.3% [95% confidence interval (CI): 21.3-27.6] and varied from 3.1% in men who had sex with men to 92.8% in injecting drug users (IDUs). The prevalence of positive HCV RNA was 17.0% [95% CI:14.7-19.4]. The prevalence of HBs antigen (Ag) or HBV DNA positivity was 7.0% [95% CI: 5.9-8.1] and varied with the continent of birth from 2.1% in Northern Africa to 10.8% in sub-Saharan Africa. The prevalence of HIV-HCV-HBV co-infection was 1.6% [95% CI: 1.0-2.4], mostly IDUs (83.3%). A severe liver disease (cirrhosis or hepatocellular carcinoma) was diagnosed in 24.7% of the positive HCV RNA patients. This study confirmed the burden of HCV infection in French HIV-infected patients and described for the first time in France the epidemiological characteristics of HIV-HBV co-infection. Furthermore, it stresses the severity of liver disease related to HCV in HIV-infected population.

Characteristics and changes in invasive meningococcal disease epidemiology in France, 2006-2015.

OBJECTIVES: This work aimed to describe the epidemiology of invasive meningococcal disease (IMD) in France, 2006-2015, including group- and genotype-specific disease burden, incidence trends before and after introduction of meningococcal C conjugate vaccines (MCCV) in 2010, and factors influencing the case fatality rate. METHODS: Mandatory notification data on incidence and IMD case characteristics were used. Genotyping of invasive strains and whole genome sequencing were performed by the French National Reference Center. Vaccination coverage was estimated from the National Health Insurance Information System's reimbursement data. RESULTS: The decrease in annual IMD incidence rates (per 100,000 inhabitants) from 1.23 in 2006 to 0.78 in 2016 was mainly related to the decrease in group B IMD. Group C incidence decreased from 0.29 in 2006 to 0.13 in 2010 but increased thereafter in age groups not targeted by MCCV. From 2010 onwards, MCCV coverage gradually increased but remained below 25% in 15-19 year-olds in 2015. Age, clinical presentation and, to a lesser extent, clonal complex 11 were the most significant factors determining mortality. CONCLUSIONS: The limited impact of vaccination on group C IMD incidence may be explained by the emergence of a new epidemic cycle in 2011 and the low vaccination coverage rates among adolescents and young adults.

Hormonal effects of flutamide in young women with polycystic ovary syndrome.

Anovulation in women with polycystic ovary syndrome (PCOS) is the direct effect of high local androgen concentrations on the ovary. Antiandrogens are substances that prevent androgens from expressing their activity on target tissues. Flutamide is a nonsteroid antiandrogen that has been found effective in hirsute patients, although its mechanism of action is unclear. Eight girls, ranging in age from 16-19 yr, with moderate to severe hirsutism and menstrual irregularities were enrolled in this study. The basal hormonal pattern showed anovulatory cycles; increased concentrations of LH, androstenedione, and testosterone; and increased LH/FSH ratio. A baseline ultrasound scan revealed polycystic ovaries in all patients. All were given 250 mg flutamide twice a day for 6 months. LH, FSH, androstenedione, testosterone, estradiol, and progesterone were evaluated before treatment, every 4 days during the third month of treatment, and on day 24 of the sixth month of treatment. Hirsutism improved, androgen levels dropped, and ovulatory cycles were restored in all subjects. Ultrasonographic examination in follicular phase showed a significant reduction in ovarian volume and ovaries of normal appearance with one dominant follicle. The most important result of the present study was that flutamide restored ovulation in anovulatory PCOS patients. This finding supports the hypothesis that flutamide reduces androgen synthesis through restoration of ovulation, although a direct block of the steroidogenic enzymes of androgen biosynthesis in ovarian thecal cells cannot be excluded.

Increased maternal serum activin A but not follistatin levels in pregnant women with hypertensive disorders.

Activin A levels are elevated in maternal serum of pregnant women with hypertensive disturbances. Because follistatin is a circulating binding protein for activin A, the present study was designed to evaluate whether serum follistatin and activin A levels also change in patients with hypertensive disorders in the last gestational trimester. The study design was a controlled survey performed in the setting of an academic prenatal care unit. Healthy pregnant women (controls, n=38) were compared with patients suffering from pregnancy-induced hypertension (PIH, n=18) or pre-eclampsia (n=16). In addition, the study included a subset of patients with pre-eclampsia associated with intrauterine growth restriction (IUGR, n=5). Maternal blood samples were withdrawn at the time of diagnosis (patients) or in a random prenatal visit (controls), and serum was assayed for follistatin and activin A levels using specific enzyme immunoassays. Hormone concentrations were corrected for gestational age by conversion to multiples of median (MoM) of the healthy controls of the same gestational age. Follistatin levels were not different between controls and patients, while activin A levels were significantly increased in patients with PIH (1.8 MoM), pre-eclampsia (4.6 MoM), and pre-eclampsia+IUGR (3.2 MoM, P<0.01, ANOVA). The ratio between activin A and follistatin was significantly increased in patients with PIH (1.5 MoM) and was further increased in patients with pre-eclampsia (4.5 MoM) and in the group with pre-eclampsia+IUGR (2.6 MoM). Follistatin levels were positively correlated with gestational age in control subjects (r=0. 36, P<0.05) and in patients with PIH (r=0.46, P<0.05) or pre-eclampsia (r=0.61, P<0.01), while activin A correlated with gestational age only in the healthy control group (r=0.69, P<0.0001). The finding of apparently normal follistatin and high activin A levels in patients with PIH and pre-eclampsia suggests that unbound, biologically active, activin A is increased in women with these gestational diseases.

Hypothalamo-pituitary-adrenal axis and adrenal function before and after ovariectomy in premenopausal women.

The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone (CRH). The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol, testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed in nine premenopausal women (44-48 years of age), before and after ovariectomy. The CRH test was performed before and 8 days after ovariectomy. A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy, whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity. The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production.

Maternal serum inhibin A levels are a marker of a viable trophoblast in incomplete and complete miscarriage.

OBJECTIVE: From early gestation the human trophoblast secretes large amounts of inhibin A and activin A, and their measurement provides a value for predicting the outcome in women who become pregnant after assisted reproductive techniques. The aim of the study was to investigate the putative role of maternal serum inhibin A and activin A levels as markers of a viable trophoblast in women who miscarry. DESIGN: Controlled cross-sectional study. METHODS: One group consisted of 65 healthy pregnant women (controls), progressing to deliver a healthy singleton baby and another group consisted of 54 miscarriages (38 incomplete (27 non-viable, 11 anembryonic pregnancies) and 16 complete). Maternal blood samples were collected between 5 and 12 weeks of gestation. RESULTS: Serum human chorionic gonadotrophin concentrations in women with incomplete or complete miscarriages were significantly (both P<0.001) lower than in controls; activin A levels being lowest only in women with a complete miscarriage (P<0.001). On the other hand, inhibin A levels were significantly lower in incomplete or complete miscarriage than in controls (both P<0.0001). CONCLUSIONS: Maternal serum inhibin A, but not activin A, determination reflects the lack of a viable trophoblast in complete miscarriage.

Role of the proteasome in the regulation of fetal fibronectin secretion in human placenta.

The goal of the current study was to examine the role of the ubiquitin-proteasome system (UPS), a pathway of intracellular degradation, in the regulation of fetal fibronectin (FFN) expression in human placenta. Primary cultures of cytotrophoblasts (CTs) and placental mesenchymal cells (PMCs) were isolated from human term placentas and were maintained in serum-free medium (SFM) in the presence of inhibitors of proteasome-mediated degradation (e.g., MG132) as well as inhibitors of other proteases. Levels of secreted FFN and interleukin (IL)-8 in culture media were quantitated by enzyme-linked immunosorbent assay (ELISA), and cell viability was assessed by trypan blue exclusion. Intracellular levels of FFN and ubiquinated proteins were measured by Western blotting, and levels of fibronectin mRNA were determined following Northern blotting. We found that proteasome inhibitors (MG132, MG262, and PSI) potently suppressed levels of secreted FFN in cultures of CTs, but they not did affect levels of IL-8. Lysosomal, calpain, and serine protease inhibitors as well as the anti-inflammatory compound sulfasalazine did not markedly affect levels of secreted FFN in CT cultures. Proteasome inhibitors did not compromise cell viability during the initial 16-18 hours of treatment and did not affect intracellular levels of FFN protein or fibronectin mRNA. The efficacy of suppression of FFN in CT culture media by proteasome inhibitors reflected their effects on intracellular accumulation of ubiquinated proteins. By contrast, the presence of proteasome inhibitors did not alter levels of secreted FFN in cultures of PMCs. We conclude that inhibitors of proteasome-mediated degradation potently and specifically suppressed extracellular expression of FFN in CTs through a cell type-specific pathway that did not involve alterations in FFN synthesis. This suggests that accumulation of ubiquinated proteins in the presence of proteasome inhibitors blocks FFN secretion or promotes the extracellular degradation of FFN. This experimental paradigm will be useful for dissecting the role of the UPS in regulating CT function.

Fetal cerebral oxygenation measured by near-infrared spectroscopy shortly before birth and acid-base status at birth.

OBJECTIVE: To test the hypothesis that the mean cerebral oxygen saturation measured by near-infrared spectroscopy shortly before delivery correlates with fetal acid-base status in umbilical cord blood. METHODS: A specially designed optical probe was inserted through the dilated cervix and placed against the fetal head during labor in 41 women. Changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations were measured continuously, and the mean cerebral oxygen saturation was determined over a 10-minute period within 30 minutes of delivery. Umbilical arterial and venous blood acid-base status was assessed immediately after birth and then correlated to the values for mean cerebral saturation. RESULTS: Values for mean cerebral oxygen saturation could be determined in 33 fetuses. Umbilical cord artery and vein pH (r = 0.82 and r = 0.79, respectively) showed significant positive correlations (P < .001), whereas base deficit (r = -0.73 and r = -0.71) and carbon dioxide pressure (r = -0.68 and r = -0.63) showed significant negative correlations (P < .001) with mean cerebral oxygen saturation measured within 30 minutes before birth. There was also a significant positive correlation between umbilical vein oxygen pressure and mean cerebral oxygen saturation (r = 0.51, P < .01). CONCLUSION: Fetal umbilical blood gas and acid-base status at birth showed significant correlations with mean cerebral oxygen saturation measured shortly before delivery. Low values for saturation were related to both respiratory and metabolic acidemia.

Growth hormone secretion in premenopausal women before and after ovariectomy: effect of hormone replacement therapy.

OBJECTIVE: To evaluate the GH response to growth hormone-releasing hormone (GH-RH) stimulation in premenopausal women before and after ovariectomy and after 1 month of estrogen replacement therapy (ERT). PATIENTS: Ten women 42 to 49 years of age awaiting combined hysterectomy and ovariectomy for a variety of benign gynecological conditions. INTERVENTION: Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, P, and PRL. Stimulation with GH-RH was performed before and 8 to 10 days after ovariectomy, and after a month of ERT. RESULTS: A significant reduction in GH response to GH-RH was observed after ovariectomy. Estrogen replacement therapy restored GH response to presurgical levels. CONCLUSIONS: The results support the role of E2 in the stimulated secretion of GH and suggest that ERT increases pituitary stores of GH.

Low estrogen oral contraceptives and the hypothalamo-pituitary axis.

The hypothalamo-pituitary axis in a group of 10 women (17-25 years of age) taking low-dose-estrogen oral contraceptives (20 micrograms ethinylestradiol (EE) + 150 micrograms desogestrel) for at least 6 months was investigated. The subjects underwent the GnRH (50 micrograms) and TRH (200 micrograms) stimulation tests for the evaluation of LH, FSH, Pr1, TSH and GH secretion. In the basal blood sample, E2, P, free T, A and SHBG levels were also determined. An elevation in LH response to GnRH was found, whereas FSH was inhibited. After TRH administration, the Pr1 response was the same in the oral contraceptive cycle as in the pretreatment cycle. Similar results were observed after TSH. Significantly, GH responded to TRH stimulation in the oral contraceptive cycles, but not in the pretreatment cycles. These results show that the new combination of 20 micrograms EE and desogestrel blocks hypothalamic production of GnRH. The different response to GnRH of LH and FSH reveals a differentiated sensitivity to the oral contraceptive which seems to inhibit the pituitary FSH-secreting gonadotrope cells in particular.

Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women.

The effects of 6 months of combined hormone therapy with transdermal estradiol (0.05 mg/day x 21 days) and different oral progestogens (10 mg/day medroxyprogesterone acetate [MPA] in the last 12 days, 10 mg/day dihydrogesterone in the last 12 days, and 50 mg/day cyproterone in the first 10 days), on menopausal symptoms and hypothalamo pituitary-ovarian function were studied in normal perimenopausal women. The study included 38 perimenopausal women, aged 43-49 years, with regular cycles of 26-32 days in length and menopausal symptoms. Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, and P every week until menstrual bleeding, before and during the first month of therapy. Plasma levels of LH and FSH were suppressed in the first month of therapy while E2 had a mean value of 45 +/- 12 pg/ml. Ultrasound examination and low levels of P indicated a complete block of ovulation and hypothalamo-pituitary-ovarian activity. All women reported the disappearance of vasomotor symptoms and nocturnal sweating. Transdermal estradiol and oral progestogens were well tolerated. This study shows that combined hormone therapy with low doses of transdermal estrogen patches and different oral progestogens reduces menopausal symptoms and also safeguards against unwanted pregnancies in the perimenopausal period.