Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection.

Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy.

[HUMAN CYTOMEGALOVIRUS INFECTION AND SPONTANEOUS ABORTION IN PREGNANT WOMEN OF I AND II TRIMESTER].

The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active CMVI were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used.

Prevalence of HHV-6 in endometrium from women with recurrent implantation failure.

PROBLEM: To study the prevalence of HHV-6 in endometrial biopsies among women experiencing recurrent implantation failure (RIF) after IVF/ET compared with controls. METHOD OF STUDY: Thirty women experiencing RIF after IVF/ET and 10 fertile women participated in the study. All women had endometrial biopsies taken in the luteal phase of their menstrual cycle for an endometrial immune profile (EIP) and HHV-6 mRNA as well as lymphocyte and granulocyte populations. The prevalence of HHV-6 in endometrial biopsies was determined, and biopsies for positive and negative expression of HHV-6 were compared with the results of their EIP and lymphocyte and granulocyte populations. RESULTS: Thirty-seven percentage of women with a history of RIF and 0% of controls demonstrated the presence of HHV-6 in their endometrial biopsies. No associations were found when the results of the endometrial immune profile were compared with the presence or absence of HHV-6. Significant increase in neutrophil-specific CD16b mRNA was found in HHV-6-positive samples, and the levels of B cells-related CD19 mRNA were lower in biopsies from women with RIF in comparison with normal controls. CONCLUSION: HHV-6 infection is an important factor in RIF.

The use of heparin in infertility and recurrent pregnancy loss: Are its antiviral properties at play?

Recently, human herpesvirus 6 (HHV-6) has been implicated in cases of poor pregnancy outcomes. The ability of HHV-6 to disrupt endothelial cell functioning may inhibit the creation of an appropriate uterine environment for implantation and fetal development, resulting in infertility and pregnancy loss, among other complications. Heparin has been used to treat pregnant women who are predisposed to thrombosis, and it has also been used in some women with infertility or recurrent pregnancy loss without associated thrombotic events. Positive pregnancy outcomes after heparin treatment in these groups indicate that heparin may alter the uterine environment to make it more suitable for implantation and fetal growth. In this paper, we propose that in some cases, heparin may accomplish this by inhibiting HHV-6 transfer to the endometrium and/or by offsetting the virally-mediated effects of endothelial cell injury.

Serological study of parvovirus B19 infection in women with recurrent spontaneous abortions.

The feto-pathogenic association of parvovirus B19 (B19) has been sparingly studied in women with abortion, but not in women with recurrent spontaneous abortions (RSA). Serum samples from 116 women with RSA who were pre-screened for S-TORCH, Chlamydia trachomatis infections, anatomical, chromosomal, endocrinal abnormality and Rh incompatibility and those who had no such known causes of abortion were included in the study. Sera were also collected from 136 normal pregnant women and 120 normal non-pregnant women as disease and normal control respectively. All sera were tested at 1:400 dilutions for B19 IgM by in-house ELISA using cloned and baculovirus expressed VP1 and VP2 antigens of B19. The frequency of anti-B19 IgM antibodies in women with RSA was 19.8%, in pregnant females it was 11% and in normal non-pregnant female was 5%. Sera of 23 women with RSA which were positive for B19 IgM tested negative for B19 DNA by PCR. Patients with RSA should be screened for B19 infection and guidelines for treatment should emerge.

Seroprevalence of rubella in pregnant women in Kashmir.

The present study was conducted to determine the seroprevalence of rubella in pregnant women in Kashmir. One thousand nine hundred and eighteen pregnant women in age group of 20-35 were divided into two groups. Group I (n=892) consisted of women with previous history of repeated abortion (507), single abortion (220), intrauterine death (149), stillbirth (14) and premature delivery (2). Group II (n=1028) pregnant women with previous normal delivery. A total of 1918 pregnant women were screened for rubella IgM antibodies out of which 16.74% were positive. In women with bad obstetric history (Group I) 26.12% were positive as compared to 8.96% in women with no significant obstetric history (Group II). The IgM antibody positivity was higher in women with previous history of intrauterine death (IUD) 58.38% followed by stillbirth 57.14%, premature delivery 50%, abortion 21.8% and recurrent abortion 17.55%. The high prevalence of disease in this region demands urgent needs for prevention. Moreover antenatal cases should be screened as early diagnosis and time intervention will help in proper management of these cases.

Waterborne viruses associated with repeated abortion.

In this study we tried to find the role of some waterborne viruses in repeated abortion of women. The study includes maternal blood serum and fetal tissue. The serum of full-term delivered women was taken as a control. All collected samples were inoculated on BGM and Hep2G cells to detect entero and Hepatitis E viruses. Enzyme-linked immunosorbent assay was also carried out for IgM and IgG antibodies against HEV in all serum samples. HEV-Ag was determined by dot-ELISA, which used also for enterovirus typing. Reverse transcriptase polymerase chain reaction was used for detection of entero and HE virus RNAs in the collected serum samples. To follow up the source of virus transmission, the wastewater treatment plant which serves the area of samples population was studied at the intake and the final effluent for the presence of hepatitis E virus and enteroviruses with special reference to coxsackieviruses. Wastewater samples were collected for 1 year and for enterovirus concentration the adsorption-elution on nitrocellulose membrane was used and for HEV, two methods of virus concentration were used, urea arginine phosphate buffer (U-APB) and PEG8000. The results of HEV investigation of aborted women sera was 22% for IgG, 3% for IgM, 20% HEV-Ag, and 16% of HEV-RNA by RT-PCR. For fetal tissue, HEV-Ag was detected in 5% of the collected samples. The detected enteroviruses were coxsackieviruses types 2, 3,4 and 5 in all serum samples and wastewater samples. The results showed also, that virus concentration by U-APB is much better than PEG-8000 but not highly efficient.

Relevance of parvovirus B19, herpes simplex virus 2, and cytomegalovirus virologic markers in maternal serum for diagnosis of unexplained recurrent abortions.

CONTEXT: The impact of viral infections during pregnancy on adverse pregnancy outcomes is not understood fully. OBJECTIVE: To assess the frequency of parvovirus B19, herpes simplex 2, and cytomegalovirus infections in relation to late abortions, in sera from Egyptian pregnant women to establish basic knowledge for future pregnancy care. In addition, to study the diagnostic value of specific immunoglobulin M (IgM) against those viruses compared with their genomes detection by polymerase chain reaction in maternal serum as a noninvasive method of laboratory diagnosis. DESIGN: Patients were recruited at the Women's Clinic, Mansoura University. One group of patients with recurrent spontaneous abortions (RSA) and a second group of pregnant women without a history of RSA were evaluated including demographic, medical, and clinical data. Virologic markers were evaluated for specific IgM and for viral DNA to cytomegalovirus, herpes simplex virus 2, and parvovirus B19. RESULTS: There was a statistically significant difference between the RSA group and the pregnant women without RSA group in frequency of parvovirus IgM (84% and 16.7%, respectively) (P < .001) and herpes simplex IgM (40% for RSA) (P = .001). Parvovirus B19 viremia was positive in 48% RSA, herpes simplex virus 2 was positive in 32% RSA, and cytomegalovirus was positive in 12% RSA patients. For RSA patients with parvovirus viremia, the mean +/- SD of IgM value was 78.5 +/- 30.12 IU/mL, and for RSA patients with negative viremia it was 30.02 +/- 17.64 IU/mL with statistically significant difference between both levels (P < .001). CONCLUSIONS: From this study, we conclude that viral infections with parvovirus B19 and herpes simplex 2 were frequently associated with recurrent abortions, and careful investigation for this condition must include evaluating these patients for the previously mentioned viruses. Serologic study by specific IgM for parvovirus and herpes simplex seem to be reliable as screening tests for high-risk pregnancy.

Anti-cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2-glycoprotein I cofactor or features of antiphospholipid syndrome.

BACKGROUND: Although controversial, some authorities have implicated hepatitis C virus (HCV) as a cause of anti-phospholipid syndrome (APLS). Anti-cardiolipin antibodies (anti-CLAbs) in APLS are cofactor-dependent ('pathogenic' antibodies). We conducted a study in order to determine the prevalence of anti-CLAbs in HCV patients, and furthermore to address whether these autoantibodies are cofactor-dependent or not and whether they are associated with features of APLS. Patients with hepatitis B virus (HBV) were also evaluated in order to assess whether there are differences in the prevalence and the clinical significance of anti-CLAbs between these two major types of chronic viral hepatitis. MATERIALS AND METHODS: One hundred and seventy-four consecutive HCV patients, 50 HBV patients and 267 healthy were investigated for the presence of anti-CLAbs and antibodies against beta2-glycoprotein I (beta2-GPI), which is the most important cofactor of the 'pathogenic' anti-CLAbs in APLS. IgG anti-CLAbs were determined by an in-house quantitative ELISA and anti-beta2-GPIAbs using a commercial ELISA kit. RESULTS: 21.3% of the HCV and 14% of the HBV patients tested positive for IgG anti-CLAbs (P < 0.0001 compared with healthy controls). Neither age, sex, certain epidemiologic and laboratory parameters nor the clinical status and the histologic findings were associated with anti-CLAbs detection in both diseases. 2.3% of the HCV (P < 0.05 compared with healthy controls) and 2% of the HBV patients tested positive for anti-beta2-GPIAbs. Presence of anti-CLAbs was not associated with features of APLS. CONCLUSIONS: A significant proportion of the HCV and HBV patients had detectable IgG anti-CLAbs. However, the anti-CLAbs titres were relatively low, and in most cases seem to be cofactor-independent ('nonpathogenic'). The latter is further supported by the lack of their association with clinical features of APLS. Furthermore, anti-CLAbs appear to be detected irrespective of the demographic, laboratory, clinical and histologic status in both HCV and HBV. However, prospective studies of longer duration may be required in order to address whether anti-CLAbs in patients with chronic viral hepatitis are or are not of clinical importance.

Seropositivity of cytomegalovirus, parvovirus and rubella in pregnant women and recurrent aborters in Leningrad County, Russia.

BACKGROUND: The objectives of this paper were to assess the prevalence of different viral infections in relation to late abortions, stillbirths, and congenital malformations in sera from Russian pregnant women and recurrent aborters in order to establish basic knowledge for future pregnancy care. METHODS: Patients were recruited at the Women's Clinic, Leningrad Regional Hospital during the period March-June 1995. One group of normally pregnant women (Group 1; n=182) and one group of recurrent aborters (Group 2; n=127) were evaluated, including demographic, medical, clinical, and serological data. RESULTS AND CONCLUSIONS: The mean age of the two groups was 27.1 and 28.2 years, respectively. The mean number of deliveries was low (0.4 and 0.5, respectively). Thirty-one point six percent of Group 1 and 41.9% of Group 2 were daily smokers. The group of normally pregnant women had a significantly increased frequency of induced abortions compared to the recurrent aborters, while the recurrent aborters reported more genital infections. There was little difference in total antibodies to cytomegalovirus (CMV) (78.0% and 81.1%, respectively) or B19 IgG (75.3% and 66.9%, respectively) between the groups, while the normal pregnant women had a significantly higher prevalence of rubella antibodies (77.5% and 59.8%, respectively). Our results indicate that less women remain susceptible to primary CMV infection in pregnancy in Russia compared to western Europe and North America. The prevalence of B19 IgG was slightly lower than data from Sweden. Natural immunization against rubella virus was lower than in other, unvaccinated female populations. Vaccination strategies for rubella are now initiated in the Russian Federation. Results from this study are utilized in a federally supported, comprehensive pregnancy care project of North-West Russia.