Intrauterine infections - challenges in the perinatal period (literature review).

The purpose of the study is to summarize the literature data on the state of intrauterine infections that cause antenatal fetal abnormalities. MATERIALS AND METHODS: This article presents the assessment of 25 world literature sources from 2000 to 2016, which discuss the etiology of infectious agents acting on the fetus and causing a variety of pathological conditions. RESULTS: During gestation many researchers refer to the infection as one of the causes of antenatal fetal abnormalities. The etiology of intrauterine infection is diverse and differs between countries with different economic conditions. Detection of an infectious agent makes it possible to promptly carry out preventive measures, to improve hygiene standards in order to reduce the rate of infection transmission from mother to fetus. CONCLUSION: Timely detection of the etiology of intrauterine infections promotes the identification of high-risk groups giving a possibility to provide treatment in order to prevent the transmission of an infectious agent having direct economic benefits, especially in resource-poor countries with low and middle income.

Uterine infection with bovine herpesvirus type 4 in dairy cows.

Diseases of the reproductive tract are a frequent problem in dairy herds. Herpesviruses are uterine pathogens also involved in other clinical diseases; for example, bovine herpesvirus type 4 BoHV-4 induces abortion, enteritis, metritis, pneumonia and vaginitis, but it can also be detected in healthy cows. The role of BoHV-4 in the development of clinical endometritis (CE) or subclinical endometritis (SE) has not clearly been described. Therefore, the objective of this study was to describe the prevalence of uterine BoHV-4 infection and its relationship with clinical, bacteriological and cytological findings in dairy cows 20-30 days after calving. The experiment was performed as a completely randomized block design, with farm (n = 10) as blocking criterion and with cow (n = 397) as the experimental unit. Logistic regression models were used to assess the effect of BoHV-4 infection on CE, SE and reproductive performance. Proportion of cows infected with BoHV-4 was 5.8% (n = 23/397). BoHV-4 was isolated in 11.0% (n = 12/109), 4.8% (n = 4/84) and 3.6% (n = 7/194) of cows diagnosed as CE, SE or healthy, respectively. A logistic model revealed that BoHV-4 infection showed a tendency to increase the risk for CE (AOR = 2.17; p = .10) but significantly reduced both, the odds for artificial insemination within 80 days post-partum (dpp) (AOR = 0.37; p = .035) and for pregnancy within 200 dpp (AOR = 0.13; p = .004). Furthermore, BoHV-4 infection increased the chance for intrauterine infection with Trueperella pyogenes (AOR = 5.55; p < .001) and vice versa (AOR = 5.79, p < .001). In conclusion, BoHV-4 infection is associated with reduced chances for insemination and pregnancy by 200 dpp and showed a trend to be associated with increased risk for CE. Furthermore, BoHV-4 and Trueperella pyogenes infections are strongly related.

Genomic diversity and phylogenetic relationships of human papillomavirus 16 (HPV16) in Nepal.

OBJECTIVES/BACKGROUND: Sequence variants in HPV16 confer differences in oncogenic potential; however, to date there have not been any HPV sequence studies performed in Nepal. The objective of this study was to characterize HPV16 viral genome sequences from Nepal compared to a reference sequence in order to determine their lineages. Additionally, we sought to determine if five High-grade Squamous Intraepithelial Lesion (HSIL) subjects were genetically distinct from the non-HSIL subjects. METHODS: DNA was isolated from exfoliated cervical cells from 17 individuals in Nepal who were previously identified to be HPV16-positive. A custom HPV16 Ion Ampliseq panel of multiplexed degenerate primers was designed that generated 47 overlapping amplicons and covered 99% of the viral genome for all known HPV16 variant lineages. All sequence data were processed through a custom quality control and analysis pipeline of sequence comparisons and phylogenetic analysis. RESULTS: There were high similarities across the genomes, with two major indels observed in the non-coding region between E5 and L2. Compared to the PAVE reference HPV16 genome, there were up to 9, 4, 38, 27, 8, 7, 52, and 32 nucleotide variants in the E6, E7, E1, E2, E4, E5, L2, and L1 genes in the Nepalese samples, respectively. Based on sequence variation, HPV16 from Nepal falls across the A, C, and D lineages in this study. We found no evidence of genetic distinctness between HSIL and non-HSIL subjects. CONCLUSIONS: The evolutionary and pathological characteristics of the representative HPV16 genomes from Nepal seem similar to results from other parts of the world and provide the basis for further studies.

Hepatitis B (HB) immunoglobulin plus HB vaccine for intrauterine HB virus infection.

BACKGROUND: Vaccination against hepatitis B virus (HBV) infection in infants born to hepatitis B surface antigen (HBsAg)-positive mothers using HB immunoglobulin (HBIG) and hepatitis B (HB) vaccine was launched in Japan in 1985. Infants testing positive for HBsAg at 1 month of age are considered to have prenatally acquired the infection and are usually excluded from the prevention program. Infants born to HB e antigen (HBeAg)-positive mothers are at a high risk of perinatally acquiring the infection. In this study, long-term outcome was evaluated in children with prenatal HBV infection who received the HBIG and HB vaccine in Japan. METHODS: Newborns of both HBsAg- and HBeAg-positive carrier mothers received HBIG within 48 h of birth and at 2 months of age. Subsequently, three doses of recombinant HB vaccine were given at 2, 3, and 5 months of age. Outcome was compared between the following two groups: infants who completed the vaccination program, even if they were HBsAg positive at 1 month of age (n = 15), and infants who did not (n = 51). RESULTS: Seroconversion from HBeAg to anti-HBe antibody (HBeAb) before 3 years of age was observed in five children (33%) who completed the vaccination program and in two (4%) who did not (P = 0.005). In 2/5 children who completed the vaccination program and achieved HBeAb seroconversion, seroconversion from HBsAg to anti-HBs antibody was also noted. CONCLUSION: This specific vaccination program for children with prenatal HBV infection has the potential to alter immune tolerance to HBV.

A live-attenuated and an inactivated chimeric porcine circovirus (PCV)1-2 vaccine are both effective at inducing a humoral immune response and reducing PCV2 viremia and intrauterine infection in female swine of breeding age.

The objective of this pilot study was to determine the efficacy of inactivated (1 or 2 dose) and live-attenuated chimeric porcine circovirus (PCV)1-2 vaccines in sows using the PCV2-spiked semen model. Thirty-five sows were randomly divided into 6 groups: negative and positive controls, 1 dose inactivated PCV1-2 vaccine challenged (1-VAC-PCV2), 2 dose inactivated PCV1-2 vaccine challenged (2-VAC-PCV2), 1 dose live-attenuated PCV1-2 vaccine unchallenged (1-LIVE-VAC), and 1 dose live-attenuated PCV1-2 vaccine challenged (1-LIVE-VAC-PCV2). The inactivated PCV1-2 vaccine induced higher levels of PCV2-specific antibodies in dams. All vaccination strategies provided good protection against PCV2 viremia in dams, whereas the majority of the unvaccinated sows were viremic. Four of the 35 dams became pregnant: a negative control, a positive control, a 2-VAC-PCV2 sow, and a 1-LIVE-VAC-PCV2 sow. The PCV2 DNA was detected in 100%, 67%, and 29% of the fetuses obtained from the positive control, inactivated vaccinated, or live-attenuated vaccinated dams, respectively. The PCV2 antigen in hearts was only detectable in the positive control litter (23% of the fetuses). The PCV1-2 DNA was detected in 29% of the fetuses in the litter from the 1-LIVE-VAC-PCV2 dam. Under the conditions of this pilot study, both vaccines protected against PCV2 viremia in breeding age animals; however, vertical transmission was not prevented.

L'objectif de cette étude pilote était de déterminer l'efficacité de vaccins inactivés (1 ou 2 doses) et vivants atténués chimériques du circovirus porcin (PCV)1-2 chez des truies en utilisant le modèle de semence inoculée avec PCV2. Trente-cinq truies ont été réparties de manière aléatoire en six groupes : témoins négatif et positif, 1 dose de vaccin PCV1-2 inactivé et challengé (1-VAC-PCV2), 2 doses de vaccin PCV1-2 inactivé et challengé (2-VAC-PCV2), 1 dose de vaccin PCV1-2 vivant atténué non-challengé (1-LIVE-VAC), et 1 dose de vaccin PCV1-2 vivant atténué et challengé (1-LIVE-VAC-PCV2). Le vaccin PCV1-2 inactivé a induit des niveaux plus élevés d'anticorps anti-PCV2 spécifiques chez les truies. Toutes les stratégies de vaccination ont entrainé une bonne protection contre une virémie par PCV2 chez les truies, alors que la majorité des truies non-vaccinées étaient virémiques. Quatre des 35 truies sont devenues gestantes : une truie témoin négatif, une truie témoin positif, une truie 2-VAC-PCV2, et une truie 1-LIVE-VAC-PCV2. L'ADN du PCV2 a été détecté chez, respectivement, 100 %, 67 %, et 29 % des fœtus obtenus des truies témoin positif, vaccin inactivé ou vaccin vivant atténué. L'antigène PCV2 dans le cœur n'était détectable que dans les portées des témoins positifs (23 % des fœtus). L'ADN de PCV1-2 a été détecté chez 29 % des fœtus dans la portée d'une truie 1-LIVE-VAC-PCV2. Dans les conditions de cette étude pilote, les deux vaccins étaient protecteurs contre une virémie par PCV2 chez des animaux en âge de se reproduire; toutefois ils n'empêchaient pas la transmission verticale.(Traduit par Docteur Serge Messier).

Viral infection of the pregnant cervix predisposes to ascending bacterial infection.

Preterm birth is the major cause of neonatal mortality and morbidity, and bacterial infections that ascend from the lower female reproductive tract are the most common route of uterine infection leading to preterm birth. The uterus and growing fetus are protected from ascending infection by the cervix, which controls and limits microbial access by the production of mucus, cytokines, and antimicrobial peptides. If this barrier is compromised, bacteria may enter the uterine cavity, leading to preterm birth. Using a mouse model, we demonstrate, to our knowledge for the first time, that viral infection of the cervix during pregnancy reduces the capacity of the female reproductive tract to prevent bacterial infection of the uterus. This is due to differences in susceptibility of the cervix to infection by virus during pregnancy and the associated changes in TLR and antimicrobial peptide expression and function. We suggest that preterm labor is a polymicrobial disease, which requires a multifactorial approach for its prevention and treatment.

High-risk human papillomavirus-induced expression of endothelial and inducible nitric oxide synthase in human uterine cervix.

INTRODUCTION: Levels of nitric oxide metabolites are elevated in the cervical fluid of women with high-risk human papillomavirus (hrHPV). To elucidate the origin of this elevation we studied the cervical expression and localization of endothelial and inducible nitric oxide synthases (eNOS, iNOS) in women. MATERIAL AND METHODS: Expression of eNOS and iNOS was studied by Western blotting in the uterine cervixes of 86 women with (n = 41) and without (n = 45) hrHPV infection. The localization of eNOS and iNOS in cervical cells was studied by immunohistochemistry in 32 randomly selected women. RESULTS: Expression of eNOS and iNOS (in mean [95% CI] density units relative to actin) was higher in women with hrHPV versus those without (eNOS: 33.8 [22.5-45.1] versus 20.2 [6.1-34.3], P = 0.007; iNOS: 12.0 [7.1-16.9]) versus 5.6 [2.0-9.2], P = 0.003). Smoking reduced 64% eNOS (P = 0.001) and 68% iNOS (P = 0.008) in women with hrHPV. Endothelial NOS was localized in the vascular endothelium, while iNOS was present in basal squamous epithelial cells. Low-grade histological lesions were accompanied by elevated expression of both eNOS and iNOS. CONCLUSIONS: High-risk HPV-associated elevation in cervical fluid nitric oxide metabolites results from both eNOS and iNOS stimulation. However, smoking seems to suppress this stimulation in hrHPV-infected women.

Goat uterine epithelial cells are susceptible to infection with Caprine Arthritis Encephalitis Virus (CAEV) in vivo.

The aim of this study was to determine, using immunofluorescence and in situ hybridization, whether CAEV is capable of infecting goat uterine epithelial cells in vivo. Five CAEV seropositive goats confirmed as infected using double nested polymerase chain reaction (dnPCR) on leucocytes and on vaginal secretions were used as CAEV positive goats. Five CAEV-free goats were used as controls. Samples from the uterine horn were prepared for dnPCR, in situ hybridization, and immunofluorescence. The results from dnPCR confirmed the presence of CAEV proviral DNA in the uterine horn samples of infected goats whereas no CAEV proviral DNA was detected in samples taken from the uninfected control goats. The in situ hybridization probe was complementary to part of the CAEV gag gene and confirmed the presence of CAEV nucleic acids in uterine samples. The positively staining cells were seen concentrated in the mucosa of the lamina propria of uterine sections. Finally, laser confocal analysis of double p28/cytokeratin immunolabelled transverse sections of CAEV infected goat uterus, demonstrated that the virus was localized in glandular and epithelial cells. This study clearly demonstrates that goat uterine epithelial cells are susceptible to CAEV infection in vivo. This finding could help to further our understanding of the epidemiology of CAEV, and in particular the possibility of vertical transmission.

Efficacy of peripartum antiviral treatment for hepatic failure due to hepatitis B virus.

OBJECTIVE: To investigate the efficacy of oral nucleosides in preventing hepatic failure during pregnancy (HFP) caused by hepatitis B virus (HBV) infection. METHODS: Besides receiving standard treatment, 70 women with HFP caused by HBV infection joined a study group (n = 40) or a control group (n = 30) according to their preference. In the study group, 14 women were given lamivudine in the third trimester and an antiviral treatment was continued postpartum. The 26 remaining patients were treated postpartum only, with lamivudine (n = 16) or entecavir (n = 10). RESULTS: In the study group, the values for serum HBV DNA and hepatitis B envelope antigen were markedly lower at 1 and 2 months than they were at baseline (P < 0.001 and P < 0.001, respectively). Moreover, the HBV DNA values at 1 and 2 months were significantly lower in the study than in the control group (P < 0.05). Overall mortality and incidence of intrauterine infection were also significantly lower in the study group (P < 0.05). No newborns had any apparent abnormalities in either group. CONCLUSION: Treatment with nucleosides suppressed the replication of HBV DNA and led to biochemical improvement. It also reduced maternal mortality and safely decreased mother-to-child HBV transmission.

The study on role of peripheral blood mononuclear cell in HBV intrauterine infection.

OBJECTIVE: To explore the role of mother's peripheral blood mononuclear cell (PBMC) infected with hepatitis B virus (HBV) in intrauterine transmission. METHODS: We have selected 60 cases of pregnant women with negative serum HBV DNA and positive PBMC HBV DNA from hospitalized patients. These women and their neonates acted as the experimental group. Twenty cases of pregnant women with HBV serum marker negative were selected. These women and their neonates served as the control group. Immunohistochemistry was employed to detect the expressions of HBsAg and HBcAg in cells of every placental layer and CD68 cells of placenta of the pregnant women whose neonates' PBMC HBV DNA was positive and/or whose neonates' serum HBV DNA positive. RESULTS: In the experimental group, neonatal serum HBV DNA of only four cases were positive, only eight cases' neonatal PBMC HBV DNA were positive and four cases had HBV DNA positive in both neonatal serum and PBMC. The expressions of HBsAg and HBcAg were detected in CD68 cells of villous stroma and blood capillary in only eight cases of neonatal placenta with positive PBMC HBV DNA. HBV infection was found in cells of every layer in placenta in two of four cases with neonatal serum HBV DNA positive. The expressions of HBsAg and HBcAg were detected in trophoblastic cells, CD68 cells of villous stroma and blood capillary in two of four cases with HBV DNA positive in both neonatal serum and PBMC. In control group, no positive signals were detected in neonates and placenta. CONCLUSION: HBV-infected PBMC in pregnant women may lead to intrauterine infection.

[Pregnant women hepatitis B markers investigation and analysis of intrauterine infection].

OBJECTIVE: To investigate the relationship between the hepatitis B virus (HBV) infection in pregnant women and intrauterine infection in local region. METHODS: The markers of hepatitis B (HBVM) were determined by time-resolved fluoroimmunoassay and HBV-DNA were determined by FQ-PCR. RESULTS: A total of 1262 pregnant women were examined the HBVM, 2.6%, 38.2%, 0.9%, 22.6%, 23.1% subjects were identified HBsAg, HBsAb, HBeAg, HBeAb, HBcAb positive respectively. In 33 cases of serum HBsAg-positive pregnant women, HBV-DNA were observed in most of 11 cases of pregnant women with HBeAg-positive and intrauterine infection rates were 6/11. In contrast, 22 cases of pregnant women with HBeAg negative, HBV-DNA were detected lowly-loaded and intrauterine infection rates were 2/22 (P < 0.01). Intrauterine infection rates of HBV in pregnant women with HBsAg-positive were 24.2% (8/33). CONCLUSION: HBV infective rates in pregnant women in the local region were low. Pregnant women with serum HBeAg positive and HBV-DNA high-loaded were prone to intrauterine infection.

Bacterial infection of endometrial stromal cells influences bovine herpesvirus 4 immediate early gene activation: a new insight into bacterial and viral interaction for uterine disease.

Experimental infection with the gamma-herpesvirus bovine herpesvirus 4 (BoHV-4) rarely establishes disease, yet BoHV-4 is commonly associated with uterine disease in cattle. Uterine disease involves co-infection with bacteria such as Escherichia coli, which stimulate the production of prostaglandin E(2) (PGE(2)) by endometrial cells. BoHV-4 replication depends on immediate early 2 (IE2) gene transactivation and, in the present study, PGE(2), E. coli or its lipopolysaccharide upregulated the IE2 gene promoter in uterine cells. Bacterial co-infection is important for BoHV-4 uterine disease.

[Chikungunya infection in pregnancy: Evidence for intrauterine infection in pregnant women and vertical transmission in the parturient. Survey of the Reunion Island outbreak]. / Infection à Chikungunya chez la femme enceinte et risque de transmission materno-foetale.

PURPOSE: Since February 2005, an outbreak of Chikungunya virus (CHIKV) infections occurred in Reunion Island. It is transmitted by the Aedes albopictus mosquito. Neonatal cases observations suggest possible fetal transmission during pregnancy. MATERIAL [corrected] AND METHODS. Observations made in 160 pregnant mothers infected by CHIKV between June 1, 2005 and February 28, 2006, in the south of Reunion island were recorded. RESULTS: Three of nine miscarriages before 22 weeks of gestation could be attributed to the virus. 3,829 births took place during this time. Among the 151 infected women, 118 were viremia negative at delivery, and none of the newborns showed any damage. Among the 33 with positive viremia at delivery, 16 newborns (48.5%) presented neonatal Chikungunya. DISCUSSION: Though fetal contamination risks appear to be rare before 22 weeks of gestation, they are potentially dangerous. After 22 weeks gestation, newborns infection occurs if the mother is viremia positive at delivery. Transplacental transmission is suspected, but the pathogenic mechanism remains unknown.

Prevalence of cervical and intrauterine human papillomavirus infection in the third trimester in asymptomatic women.

OBJECTIVE: To study the prevalence and association of human papillomavirus (HPV) infection in the cervix of pregnant women without visible signs of genital HPV infection undergoing cesarean delivery in the third trimester and to investigate a possible HPV transmission to the fetus. METHODS: All women underwent cesarean delivery between 37 and 40 weeks of gestation. Cervical samples were taken prior to cesarean delivery. Furthermore amniotic fluid, placental tissue, and cord blood were sampled and polymerase chain reaction (PCR) or Hybrid Capture II test (Digene Corp, Beltsville, MD) was performed to detect HPV DNA. RESULTS: We found that 56 (36.6 %) of 153 women were positive for HPV in the cervix. Logistic regression analyses showed a decrease of prevalence of HPV infection with increasing maternal age (P = .02). No HPV DNA could be detected in the amniotic fluid or cord blood, whereas eight placental specimens were positive for HPV DNA. CONCLUSION: The infection rate in women without clinical symptoms of HPV infection is high, but there was no HPV found in the amniotic fluid and in cord blood in women with subclinical infection in the third trimester.

Insights into viral transmission at the uterine-placental interface.

During human gestation, viruses can cause intrauterine infections associated with pregnancy complications and fetal abnormalities. The ability of viruses to spread from the infected mother to the fetus arises from the architecture of the placenta, which anchors the fetus to the uterus. Placental cytotrophoblasts differentiate, assume an endothelial phenotype, breach uterine blood vessels and form a hybrid vasculature that amplifies the maternal blood supply for fetal development. Human cytomegalovirus - the major cause of congenital disease - infects the uterine wall and the adjacent placenta, suggesting adaptation for pathogen survival in this microenvironment. Infection of villus explants and differentiating and/or invading cytotrophoblasts offers an in vitro model for studying viruses associated with prenatal infections.

Intrauterine cytomegalovirus infection and glycoprotein N (gN) genotypes.

BACKGROUND: Human cytomegalovirus (HCMV) clinical isolates display genetic polymorphisms, supposed to be related with strain-specific tissue-tropism and HCMV-induced immunopathogenesis. One recently discovered polymorphic gene is ORF UL73, encoding for the envelope glycoprotein gN. Among HCMV clinical strains, it shows four distinct genomic variants denoted as gN-1, gN-2, gN-3 and gN-4. OBJECTIVES: Aims of this study were to assess the prevalence of the different gN types in the populations examined and to investigate the possible relationship between genotypes and severity of congenital CMV disease. STUDY DESIGN: The gN genotyping was carried out by sequencing analysis of the HCMV ORF UL73. Comparisons were made by chi-square test and contingency tables. RESULTS: All the four gN genotypes can cause congenital infections and the overall distribution was as follows: gN-1, 23.6%; gN-2, 1.1%; gN-3, 12.9%; gN-4, 62.4%. None of them seems to be preferentially associated with vertical transmission or with acute outcome of congenital infection. However, considering the chronic outcome and long-term sequelae, there was a statistically significant (P<0.05) difference between congenitally infected infants with or without adverse chronic outcome. CONCLUSIONS: HCMV congenital infections, which displayed a prevalence of the gN-1 variants, seem to be associated with favorable chronic outcome.

Detection of a human parvovirus intrauterine infection with the polymerase chain reaction.

OBJECTIVE: To detect human parvovirus B19 intrauterine infection in pregnancy with the polymerase chain reaction (PCR). STUDY DESIGN: DNA of chorionic villi and amniotic fluid was extracted and the gene of human parvovirus B19 amplified with PCR. RESULTS: The study analyzed 61 specimens of chorionic villi and 26 specimens of amniotic fluid and found two positive specimens of chorionic villi and 1 positive specimen of amniotic fluid. CONCLUSION: The vertical transmission of human parvovirus B19 infection in early pregnancy may be a pathway of intrauterine infection. Chorionic villus sampling in early pregnancy and PCR could be developed as a method of prenatal diagnosis of human parvovirus B19 intrauterine infection.

Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection.

Human cytomegalovirus (HCMV) is the most common cause of viral intra-uterine infection. The experience with prenatal diagnosis remains limited and is based on few reports of small numbers of cases. It is thus difficult to compare the accuracy of the different tests because the groups studied were small and heterogeneous. We describe here our experience on a series of 98 pregnancies leading to HCMV congenital infection, among which 71 have been tested by amniotic fluid (AF) sampling followed by culture and/or polymerase chain reaction (PCR). Independently of the delay between AF sampling and the first HCMV IgM positive result, the mean sensitivity of both culture and PCR was around 70 per cent. The best sensitivity (95.5 per cent) was obtained after a delay > or = 6 weeks in late pregnancy (> or = 23 weeks). The present study demonstrated clearly that the delay between AF puncture and the presumed date of seroconversion is more important for sensitivity than the technique used for the diagnosis (PCR or culture). However, even in the best diagnostic conditions, negative results of HCMV culture or PCR in AF cannot formally exclude intra-uterine infection.