Fetal Infection Research Articles

Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection.

While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.

ТЕЧЕНИЕ БЕРЕМЕННОСТИ У ВИЧ-ИНФИЦИРОВАННЫХ ЖЕНЩИН

The article presents the peculiarities of pregnancy in HIV-infected women. Prevention of HIV transmission from the pregnant woman to the fetus can reduce the level of perinatal infection by more than 8%. An important aspect in preventing fetal infection is the timely registration of an HIV-infected pregnant woman in a women's clinic, the rejection of invasive prenatal diagnosis, the choice of the optimal antiviral treatment regimen and method of delivery, the prohibition of breastfeeding. The tactics of managing pregnant women with HIV infection is an urgent problem of obstetrics.

RNA-Seq of amniotic fluid cell-free RNA: a discovery phase study of the pathophysiology of congenital cytomegalovirus infection

Congenital cytomegalovirus infection is the most common perinatal infection and a significant cause of sensorineural hearing loss, cerebral palsy, and neurodevelopmental disability. There is a paucity of human gene expression studies examining the pathophysiology of cytomegalovirus infection. This study aimed to perform a whole transcriptomic assessment of amniotic fluid from pregnancies with live fetuses to identify differentially expressed genes and enriched Gene Ontology categories associated with congenital cytomegalovirus infection. Amniotic fluid supernatant was prospectively collected from pregnant women undergoing amniocentesis for suspected congenital cytomegalovirus infection because of first-trimester maternal primary infection or ultrasound features suggestive of fetal infection. Women who had received therapy to prevent fetal infection were excluded. Congenital cytomegalovirus infection was diagnosed via viral polymerase chain reaction of amniotic fluid; cytomegalovirus-infected fetuses were paired with noninfected controls, matched for gestational age and fetal sex. Paired-end RNA sequencing was performed on amniotic fluid cell-free RNA with the Novaseq 6000 at a depth of 30 million reads per sample. Following quality control and filtering, reads were mapped to the human genome and counts summarized across genes. Differentially expressed genes were identified using 2 approaches: voomWithQualityWeights in conjunction with limma and RUVSeq with edgeR. Genes with a false discovery rate <0.05 were considered statistically significant. Differential exon use was analyzed using DEXSeq. Functional analysis was performed using gene set enrichment analysis and Ingenuity Pathway Analysis. Manual curation of differentially regulated genes was also performed. Amniotic fluid samples were collected from 50 women; 16 (32%) had congenital cytomegalovirus infection confirmed by polymerase chain reaction. After excluding 3 samples without matched controls, 13 cytomegalovirus-infected samples collected at 18 to 23 weeks and 13 cytomegalovirus-negative gestation-matched controls were submitted for RNA sequencing and analysis (N=26). Ten of the 13 pregnancies with cytomegalovirus-infected fetuses had amniocentesis because of serologic evidence of maternal primary infection with normal fetal ultrasound, and 3 had amniocentesis because of ultrasound abnormality suggestive of cytomegalovirus infection. Four cytomegalovirus-infected pregnancies ended in termination (n=3) or fetal death (n=1), and 9 resulted in live births. Pregnancy outcomes were available for 11 of the 13 cytomegalovirus-negative controls; all resulted in live births of clinically-well infants. Differential gene expression analysis revealed 309 up-regulated and 32 down-regulated genes in the cytomegalovirus-infected group compared with the cytomegalovirus-negative group. Gene set enrichment analysis showed significant enrichment of multiple Gene Ontology categories involving the innate immune response to viral infection and interferon signaling. Of the 32 significantly down-regulated genes, 8 were known to be involved in neurodevelopment and preferentially expressed by the brain. Six specific cellular restriction factors involved in host defense to cytomegalovirus infection were up-regulated in the cytomegalovirus-infected group. Ingenuity Pathway Analysis predicted the activation of pathways involved in progressive neurologic disease and inflammatory neurologic disease. In this next-generation sequencing study, we revealed new insights into the pathophysiology of congenital cytomegalovirus infection. These data on the up-regulation of the intraamniotic innate immune response to cytomegalovirus infection and the dysregulation of neurodevelopmental genes may inform future approaches to developing prognostic markers and assessing fetal responses to in utero therapy.

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection†.

ObjectiveTo assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses.MethodMost infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI. We assessed FLV, the FLV to abdominal circumference (AC) ratio (FLV/AC-ratio), and the FLV to fetal body volume (FBV) ratio (FLV/FBV-ratio). As controls, we included 33 healthy fetuses. Hepatomegaly was evaluated post-mortem in 11 cases of congenital CMV infection. Parametric trend and intraclass correlation analyses were performed.ResultsThere were no significant differences in FLV between infected (n = 32) and healthy fetuses. On correcting the FLV for AC and FBV, we observed a significantly higher FLV in CMV-infected fetuses. There were no significant differences in the FLV, or the FLV/AC or FLV/FBV-ratios according to the severity of brain abnormalities. There was excellent concordance between the fetal liver weight estimated by MRI and liver weight obtained post-mortem. Hepatomegaly was not detected in any CMV-infected fetus.ConclusionIn CMV-infected fetuses, FLV corrected for AC and FBV was higher compared to healthy controls, indicating relative hepatomegaly. These parameters could potentially be used as surrogate markers of liver enlargement.

Amniocentesis to diagnose congenital cytomegalovirus infection following maternal primary infection

BACKGROUNDCongenital cytomegalovirus infection following maternal primary cytomegalovirus infection affects approximately 0.4% of newborns in the United States but may be hard to diagnose prenatally. OBJECTIVETo evaluate the current sensitivity and specificity of amniocentesis in detecting congenital cytomegalovirus infection. STUDY DESIGNSecondary analysis of a multicenter randomized placebo-controlled trial designed to evaluate whether cytomegalovirus hyperimmune globulin reduces congenital cytomegalovirus infection in neonates of individuals diagnosed with primary cytomegalovirus infection before 24 weeks of gestation. At randomization, subjects had no clinical evidence of fetal infection. Eligible subjects were randomized to monthly infusions of cytomegalovirus hyperimmune globulin or placebo until delivery. Although not required by the trial protocol, amniocentesis following randomization was permitted. The fetuses and neonates were tested for the presence of cytomegalovirus at delivery. Comparisons were made between those with and without amniocentesis and between those with cytomegalovirus-positive and negative results, using chi-square or Fisher exact test for categorical variables and the Wilcoxon rank sum test or t test for continuous variables. A P value of <.05 was considered significant. RESULTSFrom 2012 to 2018, 397 subjects were included, of whom 55 (14%) underwent amniocentesis. Cytomegalovirus results were available for 53 fetuses and neonates. Fourteen amniocenteses were positive (25%). Gestational age at amniocentesis was similar between those with and without cytomegalovirus present, as was the interval between maternal diagnosis and amniocentesis. The prevalence of fetal or neonatal infection was 26% (14/53). The neonates of all 12 subjects with a positive amniocentesis and available results had cytomegalovirus infection confirmed at delivery, as did 2 neonates from the group of 41 subjects with a negative amniocentesis, with a sensitivity of 86% (95% confidence interval, 57–98), specificity of 100% (95% confidence interval, 91–100), positive predictive value of 100% (95% confidence interval, 74–100), and negative predictive value of 95% (95% confidence interval, 83–99). Amniocentesis-positive pregnancies were delivered at an earlier gestational age (37.4 vs 39.6 weeks; P<.001) and had lower birthweights (2583±749 vs 3428±608 g, P=.004) than amniocentesis-negative pregnancies. CONCLUSIONAmniocentesis results are an accurate predictor of congenital cytomegalovirus infection.

Lessons from Ten Years' the Prevalence of Congenital Rubella Syndrome (CRS) in the Young Population Living in a Developing Country, Tehran; Iran.

A safe and effective rubella vaccine is available and prescribed in IRAN. This is a survey of CRS cases collected based on WHO criteria one decade after the MR vaccination campaign (2003). This Multi-stage prospective/cross-sectional study was carried out in three stages in 3 educational hospitals in Tehran (Rasoul Aram, Akbar Abadi, and Firoozabadi), In the first stage of the study between 2011 and 2012 total of 186 infants were evaluated, and in the second stage of the study, total 163 blood samples of infants with suspected INTRA UTERINE INFECTION were compared with a group of healthy matched infants. In the first and second stages, Rubella immunity (IgG&IgM) in cord blood was evaluated by the Eliza method. Despite MR vaccination in Iran, after one decade"confirmed CRS" and " compatible CRS" was diagnosed in 5 and 31 from 89 CRS suspected cases. The incidence of "confirmed CRS" in every 100 CRS suspected infants (after campaign) is 5.6 %, and 31 CRS Compatible cases are so important. Without active CRS surveillance, mild infection such as IUGR, hearing loss, heart abnormalities, impaired vision, and mental retardation even in the developed country might be missed. Fetal infection is persistent, which imposes additional costs on the country. Another mass vaccination in women and girls is needed. Also, the anti-rubella IgG testing before pregnancy in women who were not vaccinated; vaccination of women before marriage /pregnancy should be obligatory in order to prevent the CRS.

Congenital Cytomegalovirus

Congenital Cytomegalovirus

Concomitant pyroptotic and apoptotic cell death triggered in macrophages infected by Zika virus.

Zika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetuses. As a mosquito-borne arbovirus, it enters the bloodstream and replicates in various organs. During pregnancy, it can be transmitted from the blood of the viremic mother to the fetus by crossing the placental barrier. Monocytes and macrophages are considered the earliest blood cell types to be infected by ZIKV. As a first line defense, these cells are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV could infect and induce cell death in human and murine macrophages. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdermin D (GSDMD) as well as increased secretion of IL-1β and IL-18. This suggests that the inflammasome was activated and that may lead to pyroptosis in infected macrophages. The pyroptosis was NLRP3-dependent and could be suppressed in the macrophages treated with shRNA to target and knockdown caspase-1. It was also be inhibited by an inhibitor for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected macrophages, with two mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.

Español Peru

ABSTRACT: Objectives: To determine the association between maternal perinatal factors and early neonatal sepsis in a Chimbote hospital. Methodology: Analytical, cross-sectional, retrospective study and design of cases and controls. Fifty-one newborns with early neonatal sepsis (cases) and 51 healthy newborns (control) were compared, from the neonatology service of La Caleta hospital, period 2016-2020; using bivariate and multivariate statistics (odds ratio, 95% confidence interval, chi square and logistic regression p value). Results: The male sex was found to have an odds ratio: 2.07; 95% CI (0.93 to 4.61); prematurity odds ratio: 3.91, 95% CI (0.76 to 19.98); low birth weight odds ratio: 2.67, 95% CI (0.49 to 14.44); urinary tract infection odds ratio: 6.77, 95% CI (1.41 to 32.36); premature rupture of membranes&gt; 18 hours odds ratio: 1.98, 95% CI (0.61 to 6.37); chorioamnionitis odds ratio: Undefined, 95% CI (Undefined); meconium amniotic fluid odds ratio: 7.37, 95% CI (1.98 to 27.31), acute fetal distress odds ratio: 12.25, 95% CI (1.50 to 99.80); and dystocic delivery odds ratio: 3.50, 95% CI (1.36 to 8.99). Conclusions: Presenting meconium amniotic fluid, acute fetal distress, dystocic delivery and urinary tract infection were risk factors associated with early neonatal sepsis. The evidence analyzed was not sufficient to conclude that the sex of the neonate, low birth weight, prematurity, chorioamnionitis, and prolonged rupture of membranes were risk factors for early neonatal sepsis.

An Uncommon Cause for Respiratory Failure in a Preterm Neonate.

An Uncommon Cause for Respiratory Failure in a Preterm Neonate.

HIV medication to prevent fetal infection during pregnancy

When it has been declared a global epidemic, HIV infection became a challenge for medical world. Even if there is only one healed case cited in literature, treatment for HIV-infection have evolved during time leading to very good results in disease control and limitation of virus transmission. When it comes for viral transmission, an essential research topic became the prevention of mother to fetal transmission. In the long run, many discovered antiretroviral drugs proved to be efficient in controlling HIV infection during pregnancy and thereby in reducing the risk of viral transmission to the fetus. But along with use of the HIV-treatment in pregnancy, many questions have appeared. Are the drugs safe for the fetus, or are there any adverse pregnancy outcomes? Should the treatment be adjusted for the desired results in pregnancy, or should the initial treatment be changed when the pregnancy is diagnosed? Many retrospective or prospective observational studies and comparative studies have been conducted in order to answer those questions and to analyze the efficacy and the safety of mostly used antiretroviral drugs in pregnancy. This article reviews the existing studies, guidelines and recommendations regarding the combined antiretroviral HIV treatment during pregnancy for fetal infection prevention.

Effect of intimate hygiene fluids on the number of Listeria monocytogenes isolated from women

Introduction. Listeria monocytogenes is an etiological factor of listeriosis, widespread in the environment. The consequence of fetal infection in the second trimester of pregnancy in most cases is the death of the fetus or stillbirth. Material and methods. In this study, 7 strains of L. monocytogenes isolated from the vagina of women and the reference strain L. monocytogenes ATCC 19111 were used. The examined strains were treated with five commercially available intimate hygiene washes. The efficacy of the wash fluids used was based on the induced decrease in the number of bacteria expressed as a logarithmic colony-forming unit (CFU) × ml-1. Results. The study showed that probiotic fluid (pH = 3.5) decreased the number of bacteria by an average of 4.56 log CFU × ml-1, while wash fluid intended for pregnant and puerperal women (pH = 4.0) reduced the number of L. monocytogenes by an average of 1.55 log CFU × ml-1. Lower bactericidal efficacy was observed in the case of wash fluids intended for everyday use. The fluid containing marigold extract and the liquid with the addition of rice proteins and arnica extract decreased the number of L. monocytogenes by an average of 1.11 log CFU × ml-1, and the fluid with silver and copper nanoparticles by 1.14 log CFU × ml-1. Conclusions. Everyday use of intimate hygiene washes reduces the risk of urogenital infections in women and supports their treatment. Prevention with the use of probiotic wash solutions may reduce the number of vaginal infections caused by L. monocytogenes, which is especially important in the case of pregnant women because the number of patients diagnosed with listeriosis has increased.

Sociodemographic, living environment and maternal health associations with stillbirth in a tertiary healthcare setting in Kano, Northern Nigeria

Background&#x0D; Stillbirths are reported as one of the most neglected tragedies in global health, with around 2m stillbirths occurring annually and the majority occurring in low- and middle income countries (LMICs). Many antenatal stillbirths are due to preventable conditions such as maternal infections and non-communicable diseases. Almost half of all stillbirths occur during the intrapartum period, with many linked to obstetric complications. Known risk factors for stillbirths overall include young or advancing maternal age, fetal infection, maternal hypertensive conditions, perinatal asphyxia, history of previous stillbirth, obstetric complications, intrauterine growth restriction and abruptio placenta/placenta praevia. Common non-clinical risk factors include lack of education, socioeconomic deprivation and substandard antenatal care.&#x0D; Methods&#x0D; A single site prospective observational study conducted over three-months was conducted in a tertiary referral hospital in Kano, Nigeria. Eligible participants were mothers presenting at the site in labour and their babies.&#x0D; Demographic and clinical data were collected by paper-based questionnaires. Data were collected on living environment, health and medical history, pregnancy history and pregnancy/birth factors. Each mother answered pre-delivery questions, with potential follow-on questions dependent on birth outcome. Further data points were collected from clinical observations. Photographs were taken of stillborn babies to support data collected and to aid the UK team on classifying degrees of maceration in an attempt to identify antenatal and intrapartum fetal death.&#x0D; Findings&#x0D; Higher odds of stillbirth were associated with low levels of education, a further distance to travel from home to the hospital, living in a shack, maternal hypertension and having had a previous stillbirth after adjusting for all sociodemographic and health features. Higher odds of intrapartum stillbirth included; shoulder presentation, compound presentation and breech presentation compared to cephalic presentation. Other birth related factors associated with higher odds of stillbirth included reported birthing complications, duration of labour being &gt;=18 hours), antepartum haemorrhage, prolonged/obstructed labour, vaginal breech delivery, emergency Caesarean-section delivery, and signs of trauma to the neonate.&#x0D; ConclusionsIdentified risk factors associated with stillbirths are relatively amenable to intervention and a lot of work has been conducted globally, so the development of intervention with sufficient funding should be a relatively rapid process.&#x0D; For collaborations please contact: Email: miltonrl1@cardiff.ac.uk

206 Attention to fever! malaria in pregnancy: A case report

Introduction and aims: Malaria is the most important parasitic disease of humans, causing 10000 deaths of pregnant women each year. Pregnant women experience more severe disease with anemia, fever, preterm birth, fetal growth restriction, congenital infection and death of mother and/or fetus. One of the unique features of malaria in pregnancy is the ability of Plasmodium falciparum-parasitized erythrocytes to sequester within the intervillous space of the placenta. We intend to raise awareness to the diagnosis of malaria in pregnancy and its complications in pregnancy.

Experimental evidence for a high rate of maternal-fetal transmission of dengue virus in the presence of antibodies in immunocompromised mice

SummaryBackgroundCongenital disorders associated with prenatal vertical transmission of Zika virus (ZIKV) is well established since the 2016 outbreak in the Americas. However, despite clinical reports of similar mode of transmission for other flaviviruses such as dengue virus (DENV), the phenomenon has not been experimentally explored.MethodsPregnant AG129 mice were infected with DENV1 in the presence or absence of enhancing antibodies at different gestational time points. ZIKV was used for comparison. We quantified viral load in fetus and placentas and performed comprehensive gene expression profiling in the maternal (decidua) and fetal portion of placenta separately.FindingsWe demonstrate in a laboratory experimental setting that DENV can be transmitted vertically in a gestation stage-dependent manner similar to ZIKV, and this incidence drastically increases in the presence of enhancing antibodies. Interestingly, a high rate of DENV fetal infection occurs even though the placental viral load is significantly lower than that found in ZIKV-infected dams. Comprehensive gene expression profiling revealed DENV infection modulates a variety of inflammation-associated genes comparable to ZIKV in decidua and fetal placenta in early pregnancy.InterpretationOur findings suggest that the virus-induced modulation of host gene expression may facilitate DENV to cross the placental barrier in spite of lower viral burden compared to ZIKV. This mouse model may serve to identify the host determinants required for the vertical transmission of flaviviruses and develop appropriate countermeasures.FundingNational Medical Research Council/Open Fund Individual Research Grant MOH-000524 (SW), MOH-000086 and OFIRG20nov-0017 (SGV).

Epigenomic and Proteomic Changes in Fetal Spleens Persistently Infected with Bovine Viral Diarrhea Virus: Repercussions for the Developing Immune System, Bone, Brain, and Heart.

Bovine viral diarrhea virus (BVDV) infection during early gestation results in persistently infected (PI) immunotolerant calves that are the primary reservoirs of the virus. Pathologies observed in PI cattle include congenital defects of the brain, heart, and bone as well as marked functional defects in their immune system. It was hypothesized that fetal BVDV infection alters T cell activation and signaling genes by epigenetic mechanisms. To test this, PI and control fetal splenic tissues were collected on day 245 of gestation, 170 days post maternal infection. DNA was isolated for reduced representation bisulfite sequencing, protein was isolated for proteomics, both were analyzed with appropriate bioinformatic methods. Within set parameters, 1951 hypermethylated and 691 hypomethylated DNA regions were identified in PI compared to control fetuses. Pathways associated with immune system, neural, cardiac, and bone development were associated with heavily methylated DNA. The proteomic analysis revealed 12 differentially expressed proteins in PI vs. control animals. Upregulated proteins were associated with protein processing, whereas downregulated proteins were associated with lymphocyte migration and development in PI compared to control fetal spleens. The epigenetic changes in DNA may explain the immune dysfunctions, abnormal bone formation, and brain and heart defects observed in PI animals.

Exploring management of antenatally diagnosed fetal syphilis infection.

The incidence of syphilis among Canadian women of childbearing age has risen dramatically in the past decade, with a resurgence of infants born with congenital syphilis. While guidelines exist to guide maternal infection during pregnancy, there is little evidence available to guide management in situations where the developing fetus is found to be severely affected. Our patient presented in the second trimester of her pregnancy as syphilis contact. Positive serologic tests (venereal disease research laboratory titre of 1:64) and a chancre suggested primary infection. Ultrasound demonstrated a fetus at 19+3 weeks gestation with hydrops fetalis and a markedly abnormal brain. Amniocentesis confirmed congenital syphilis infection on polymerase chain reaction testing. After nine days of intravenous penicillin G, the fetal status had worsened, and the family ultimately chose a medical termination of the pregnancy. Evolving ultrasound technology has allowed us to identify severely affected fetuses, who may historically have been delivered stillborn. Following routine syphiliotherapy with benzathine penicillin, these abnormal ultrasound features may take weeks or months to reverse, which poses a challenge in prognostication and counselling. Case reports data suggests intensive treatment with intravenous penicillin may be effective in severe cases where fetal hydrops is present. This case highlights the potential morbidity of fetal syphilis infection and underscores the paucity of current literature. Information sharing will be essential to build a modern knowledge base on treating this ancient disease.

Stillbirth after COVID-19 in Unvaccinated Mothers Can Result from SARS-CoV-2 Placentitis, Placental Insufficiency, and Hypoxic Ischemic Fetal Demise, Not Direct Fetal Infection: Potential Role of Maternal Vaccination in Pregnancy.

Stillbirth is a recently recognized complication of COVID-19 in pregnant women. Other congenitally transmitted infections from viruses, bacteria and parasites can cause stillbirth by infecting fetal organs following transplacental transmission of the agent from the maternal bloodstream. However, recent research on pregnant women with COVID-19 having stillbirths indicates that there is another mechanism of stillbirth that can occur in placentas infected with SARS-CoV-2. In these cases, viral infection of the placenta results in SARS-CoV-2 placentitis, a combination of concurrent destructive findings that include increased fibrin deposition which typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis. These three pathological lesions, in some cases together with placental hemorrhage, thrombohematomas and villitis, result in severe and diffuse placental parenchymal destruction. This pathology can involve greater than one-half of the placental volume, averaging 77% in the largest study of 68 cases, effectively rendering the placenta incapable of performing its function of oxygenating the fetus. This destructive placental process can lead to stillbirth and neonatal death via malperfusion and placental insufficiency which is independent of fetal infection. Fetal autopsies show no evidence that direct infection of fetal organs is contributory. Because all mothers examined have been unvaccinated, maternal vaccination may prevent viremia and consequent placental infection.

In Vivo Anti-Toxoplasma Effects of Dracocephalum polychaetum Essential Oil

Background: Toxoplasma gondii is a parasite that lives inside its host cells, with cats reported as its final host. T. gondii causes toxoplasmosis infection, showing severe symptoms in infected fetuses and individuals with defective immune systems. Drugs used to treat toxoplasmosis have numerous side effects on patients, including toxicity and drug resistance. Objectives: This study aimed to investigate the same in vivo anti-Toxoplasma activity of Dracocephalum polychaetum essential oil. Moreover, this study aimed to investigate the effect of different concentrations of D. polychaetum essential oil on the survival rate of mice infected with T. gondii. Methods: The T. gondii RH strain was used in the present study. Moreover, 60 BALB/c mice aged 4 - 6 weeks with an average weight of 20 - 25 g were used to evaluate the in vivo anti-Toxoplasma effect of D. polychaetum essential oil. The BALB/c mice were divided into six groups of 10 cases. One negative control group received Phosphate buffered saline (PBS); two treatment groups received pyrimethamine (25 mg/kg) and sulfadiazine (500 mg/kg), and three other groups received 50, 100, and 200 mg/kg of essential oil, respectively. The data were analyzed with the Kaplan-Meier nonparametric method and log-rank test in SPSS software (version 16) at a significance level of 0.05. Results: The survival rate of the acutely infected mice was evaluated by the intraperitoneal injection of the essential oil (50, 100, and 200 mg/kg-1 day-1) infected with tachyzoites. There was no general significant difference between the mean survival rate of the studied groups (P &gt; 0.05). However, essential oil and negative and positive controls that showed the best anti-Toxoplasma activity were assayed in triplicate at each concentration. Conclusions: A concentration of 200 mg/kg of D. polychaetum essential oil had a greater significant anti-Toxoplasma effect than other groups.

Porcine reproductive and respiratory virus 2 infection of the fetus results in multi-organ cell cycle suppression

Porcine reproductive and respiratory syndrome virus (PRRSV) infection during late gestation negatively affects fetal development. The objective of this study was to identify the fetal organs most severely impacted following infection, and evaluate the relationship between this response and fetal phenotypes. RNA was extracted from fetal heart, liver, lung, thymus, kidney, spleen, and loin muscle, collected following late gestation viral challenge of pregnant gilts. Initially, gene expression for three cell cycle promoters (CDK1, CDK2, CDK4) and one inhibitor (CDKN1A) were evaluated in biologically extreme phenotypic subsets including gestational age-matched controls (CON), uninfected (UNIF), high-viral load viable (HV-VIA), and high-viral load meconium-stained (HV-MEC) fetuses. There were no differences between CON and UNIF groups for any gene, indicating no impact of maternal infection alone. Relative to CON, high-viral load (HV-VIA, HV-MEC) fetuses showed significant downregulation of at least one CDK gene in all tissues except liver, while CDKN1A was upregulated in all tissues except muscle, with the heart and kidney most severely impacted. Subsequent evaluation of additional genes known to be upregulated following activation of P53 or TGFb/SMAD signaling cascades indicated neither pathway was responsible for the observed increase in CDKN1A. Finally, analysis of heart and kidney from a larger unselected population of infected fetuses from the same animal study showed that serum thyroxin and viral load were highly correlated with the expression of CDKN1A in both tissues. Collectively these results demonstrate the widespread suppression in cell division across all tissues in PRRSV infected fetuses and indicate a non-canonical regulatory mechanism.