Congenital Infection In Humans Research Articles

Lymphocytic choriomeningitis virus injures the developing brain: effects and mechanisms.

Lymphocytic choriomeningitis virus (LCMV) is a prevalent pathogen, whose natural host and reservoir is the wild mouse. Humans can be infected when they contact the secretions of mice. Most infections of postnatal humans result in mild illness. However, the consequences can be severe when the infection occurs during pregnancy, as the virus crosses the placenta to infect the fetus. LCMV infection of the human fetus can lead to severe neuropathologic effects, including microencephaly, hydrocephalus, focal destructive lesions, and cerebellar hypoplasia. Outcomes among children with congenital LCMV are variable, but most are permanently and severely disabled. The neonatal rat inoculated with LCMV models human prenatal infection. The rat model has demonstrated that effects of LCMV depend on host age at the time of infection. Some effects, including encephalomalacia and neuronal migration disturbances, are immune-mediated and depend on the actions of T-lymphocytes. Other effects, including cerebellar hypoplasia, are virus-mediated and do not depend on T-lymphocytes. Cerebellar neuronal migration disturbances are caused by immune-mediated corruption of Bergmann glia structure. The rat pup inoculated with LCMV is a superb animal model for human congenital infection. All neuropathologic effects observed in human congenital LCMV infection can be recapitulated in the rat model. IMPACT: Lymphocytic choriomeningitis virus (LCMV) is a prevalent human pathogen that can cause serious neurologic birth defects when the infection occurs during pregnancy. The effects of the virus on the developing brain depend strongly on the age of the host at the time of infection. Some of the pathologic effects of LCMV are immune-mediated and are driven by T-lymphocytes, while other pathologic effects are due to the virus itself.

Knowledge of cytomegalovirus infection among women in Saudi Arabia: A cross-sectional study.

BackgroundCytomegalovirus (CMV) is the most common intrauterine congenital infection in humans. Worldwide seropositive rates of CMV are considerably high among women of childbearing age. There is currently no optimal drug treatment nor a vaccine for congenital CMV infection and therefore the best available program to date of prevention is practicing standard hygienic measures. The success of this program relies on women’s knowledge of CMV modes of transmissions, and risk and preventative behaviors.ObjectiveThe current study aims to assess the awareness and knowledge of CMV infection among women in Saudi Arabia.MethodIn this cross-sectional study, an online self-administered questionnaire was distributed to women 18 years of age or older residing in all regions of Saudi Arabia. The questionnaire included questions to assess awareness of CMV, knowledge of symptoms, transmission, and preventative measures of CMV infection.ResultsOut of the 1004 women who completed the questionnaire, self-reported knowledge of CMV was considerably low with only 82 women (8.17%) having heard of CMV infection. Most women reported learning about CMV from the internet and university. In binary logistic analyses, women pursuing studies in healthcare and those working in health professions, as well as those with undergraduate and graduate college degrees were significantly associated with higher knowledge of CMV. Urban area of residence was significantly associated with lower levels of knowledge of CMV. Among women who reported they had heard of CMV, their knowledge of CMV modes of transmission, symptoms, and preventative measures was considerably low. Regarding the transmission route, 23% reported no knowledge of modes of transmission, 59.75% reported mother-to-child transmission, 48.78% reported sexual intercourse, and 45% reported contact with body fluids of an infected person. Regarding knowledge of symptoms of congenital CMV, mental retardation and death were the most commonly reported clinical presentations.ConclusionThe current study showed that the overall knowledge of CMV is very low among women in Saudi Arabia. Working in the healthcare field and higher education levels were significantly associated with better knowledge of CMV. It is crucial that women are provided with information regarding CMV-associated complications and preventative measures against mother-to-fetus transmission of CMV.

Congenital Cytomegalovirus Infection: Transmission, Diagnosis and Treatment.

Introduction: Cytomegalovirus (CMV) is a linear, dsDNA virus that is regarded as the prototype of the Betaherpesvirinae subfamily of viruses. It has an established endemic status in certain locations around the globe, and is also reported to be the most prevalently occurring congenital infection in humans. Furthermore, Cytomegalovirus is notorious for being a persistent lifelong pathogen that poses a threat of reactivation as well. Discussion: Congenital cytomegalovirus infection causes numerous ophthalmologic, and neurologic sequelae, and is also known for being the principal reason behind sensorineural hearing loss of non-genetic etiology in neonates. These symptoms, if present, may give rise to a premonition of congenital Cytomegalovirus disease, and so, a diagnosis can be established through serology, radiology, and PCR of salivary, urinary, or dried blood spot samples. Timely administration of ganciclovir or valganciclovir has proven to be effective in managing symptomatic cases of congenital CMV. Conclusion: A well-timed delivery of pharmacological and non-pharmacological interventions is necessary to achieve healthy developmental outcomes for the neonate. Moreover, there is still a need to study the role of antiviral therapy in silent cases since asymptomatic patients are at a risk of developing long-term clinical sequelae as well. Relevance: An estimated 60-90% of women of child-bearing age get infected with Cytomegalovirus, and Congenital CMV disease is reported in 0.2-2.4% of all live births. Therefore, in order to develop effective screening and management protocols, it is vital to educate healthcare professionals regarding the various aspects of this congenital infection.

Congenital Cytomegalovirus Infection: Transmission, Diagnosis and Treatment.

Introduction: Cytomegalovirus (CMV) is a linear, dsDNA virus that is regarded as the prototype of the Betaherpesvirinae subfamily of viruses. It has an established endemic status in certain locations around the globe, and is also reported to be the most prevalently occurring congenital infection in humans. Furthermore, Cytomegalovirus is notorious for being a persistent lifelong pathogen that poses a threat of reactivation as well. Discussion: Congenital cytomegalovirus infection causes numerous ophthalmologic, and neurologic sequelae, and is also known for being the principal reason behind sensorineural hearing loss of non-genetic etiology in neonates. These symptoms, if present, may give rise to a premonition of congenital Cytomegalovirus disease, and so, a diagnosis can be established through serology, radiology, and PCR of salivary, urinary, or dried blood spot samples. Timely administration of ganciclovir or valganciclovir has proven to be effective in managing symptomatic cases of congenital CMV. Conclusion: A well-timed delivery of pharmacological and non-pharmacological interventions is necessary to achieve healthy developmental outcomes for the neonate. Moreover, there is still a need to study the role of antiviral therapy in silent cases since asymptomatic patients are at a risk of developing long-term clinical sequelae as well. Relevance: An estimated 60-90% of women of child-bearing age get infected with Cytomegalovirus, and Congenital CMV disease is reported in 0.2-2.4% of all live births. Therefore, in order to develop effective screening and management protocols, it is vital to educate healthcare professionals regarding the various aspects of this congenital infection.

Placental Autophagy and Viral Replication Co-localize in Human and Non-human Primate Placentae Following Zika Virus Infection: Implications for Therapeutic Interventions.

Multiple studies have shown both induction and inhibition of autophagy during Zika virus (ZIKV) infection. While some have proposed mechanisms by which autophagic dysregulation might facilitate ZIKV vertical transmission, there is a lack of in situ data in human and non-human primate models. This is an especially pertinent question as autophagy-inhibitors, such as hydroxychloroquine, have been proposed as potential therapeutic agents aimed at preventing vertical transmission of ZIKV and other RNA viruses. Given the paucity of pre-clinical data in support of either autophagic enhancement or inhibition of placental ZIKV viral infection, we sought to assess cellular, spatial, and temporal associations between placental ZIKV infection and measures of autophagy in human primary cell culture and congenital infection cases, as well as an experimental non-human primate (marmoset, Callithrix jacchus) model. Primary trophoblast cells were isolated from human placentae (n = 10) and infected in vitro with ZIKV. Autophagy-associated gene expression (ULK-1, BECN1, ATG5, ATG7, ATG12, ATG16L1, MAP1LC3A, MAP1LC3B, p62/SQSTM1) was then determined by TaqMan qPCR to determine fold-change with ZIKV-infection. In in vivo validation experiments, autophagy genes LC3B and p62/SQSTM1 were probed using in situ hybridization (ISH) in the placentae of human Congenital Zika Syndrome (CZS) cases (n = 3) and ZIKV-infected marmoset placenta (n = 1) and fetal tissue (n = 1). Infected and uninfected villi were compared for mean density and co-localization of autophagic protein markers. Studies of primary cultured human trophoblasts revealed decreased expression of autophagy genes ATG5 and p62/SQSTM1 in ZIKV-infected trophoblasts [ATG5 fold change (±SD) 0.734-fold (±0.722), p = 0.036; p62/SQSTM1 0.661-fold (±0.666), p = 0.029]. Histologic examination by ISH and immunohistochemistry confirmed spatial association of autophagy and ZIKV infection in human congenital infection cases, as well as marmoset placental and fetal tissue samples. When quantified by densitometric data, autophagic protein LC3B, and p62/SQSTM1 expression in marmoset placenta were significantly decreased in in situ ZIKV-infected villi compared to less-infected areas [LC3B mean 0.951 (95% CI, 0.930-0.971), p = 0.018; p62/SQSTM1 mean 0.863 (95% CI, 0.810-0.916), p = 0.024]. In the current study, we observed that in the non-transformed human and non-human primate placenta, disruption (specifically down-regulation) of autophagy accompanies later ZIKV replication in vitro, in vivo, and in situ. The findings collectively suggest that dysregulated autophagy spatially and temporally accompanies placental ZIKV replication, providing the first in situ evidence in relevant primate pre-clinical and clinical models for the importance of timing of human therapeutic strategies aimed at agonizing/antagonizing autophagy. These studies have likely further implications for other congenitally transmitted viruses, particularly the RNA viruses, given the ubiquitous nature of autophagic disruption and dysregulation in host responses to viral infection during pregnancy.

Establishment and validation of a guinea pig model for human congenital toxoplasmosis

BackgroundToxoplasma gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infection in humans and animals may lead to severe symptoms in the offspring, especially in the brain. A suitable animal model for human congenital toxoplasmosis is currently lacking. The aim of this study is to establish and validate the guinea pig as a model for human congenital toxoplasmosis by investigating the impact of the T. gondii infection dose, the duration of infection and the gestational stage at infection on the seroconversion, survival rate of dams, fate of the offspring, T. gondii DNA loads in various offspring tissues and organs and the integrity of the offspring brain.MethodsPregnant guinea pigs were infected with three different doses (10, 100, 500 oocysts) of T. gondii strain ME49 at three different time points during gestation (15, 30, 48 days post-conception). Serum of dams was tested for the presence of T. gondii antibodies using immunoblotting. T. gondii DNA levels in the dam and offspring were determined by qPCR. Offspring brains were examined histologically.ResultsWe found the survival rate of dams and fate of the offspring to be highly dependent on the T. gondii infection dose with an inoculation of 500 oocysts ending lethally for all respective offspring. Moreover, both parameters differ depending on the gestational stage at infection with infection in the first and third trimester of gestation resulting in a high offspring mortality rate. The duration of infection was found to substantially impact the seroconversion rate of dams with the probability of seroconversion exceeding 50% after day 20 post-infection. Furthermore, the infection duration of dams influenced the T. gondii DNA loads in the offspring and the integrity of offspring brain. Highest DNA levels were found in the offspring brain of dams infected for ≥ 34 days.ConclusionThis study contributes to establishing the guinea pig as a suitable model for human congenital toxoplasmosis and thus lays the foundation for using the guinea pig as a suitable animal model to study scientific questions of high topicality and clinical significance, which address the pathogenesis, diagnosis, therapy and prognosis of congenital toxoplasmosis.Graphical abstract

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection.

Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. Evidence suggests that control of neutrophil recruitment to flavivirus-infected tissues may reduce immunopathology in experimental models and patients, with minimal loss to viral clearance. Further investigation on the roles of neutrophils in flaviviral infections may reveal unappreciated functions of this leukocyte population while increasing our understanding of flaviviral disease pathogenesis in its multiple forms.

Long-Term Clinical, Audiological, Visual, Neurocognitive and Behavioral Outcome in Children With Symptomatic and Asymptomatic Congenital Cytomegalovirus Infection Treated With Valganciclovir.

Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. There are no enough data on long-term outcome of newborns with congenital CMV (cCMV) infection, particularly for those asymptomatic at birth. For this reason, we performed this study to evaluate long-term audiological, visual, neurocognitive, and behavioral outcome in patients with symptomatic and asymptomatic cCMV infection treated with oral Valganciclovir (VGC). Thirty-six newborns with confirmed cCMV infection were evaluated: 12 (33.3%) symptomatic at birth and 24 asymptomatic (66.7%). No one had cognitive impairment. Cognitive assessment scales resulted abnormal in 4/35 patients (11.4%). 11/21 patients (52.4%) achieved abnormal scores in neuropsychological tests. The language evaluation gave pathological results in 6/21 (28.5%) patients. 6/35 patients (17.1%) developed SNHL, all symptomatic at birth except one. None of the 34 patients evaluated developed CMV retinopathy. Our study shows that both symptomatic and asymptomatic newborns with cCMV infection develop long-term sequelae, particularly in the behavioral and communicative areas, independently from the trimester of maternal infection.

LB20. Valacyclovir to Prevent Vertical Transmission of Cytomegalovirus After Maternal Primary Infection During Pregnancy

BackgroundCytomegalovirus (CMV) is the most common cause of congenital infection in humans. The highest risk of fetal injury follows a maternal primary infection early in pregnancy. Despite the potential for severe fetal injury, to date there are no proven means to prevent viral transmission. Valacyclovir is an antiviral drug proven effective in decreasing the risk for CMV infection among transplant recipients. Valacyclovir is safe for use in pregnancy, and concentrates in the amniotic fluid without accumulating. A dose of 8 g/day creates therapeutic drug levels in the amniotic fluid and fetal blood.MethodsThis is a randomized, double-blind, placebo-controlled study comprising pregnant women with serologic evidence of primary CMV infection during the periconceptional period and first trimester. After informed consent, patients were randomly assigned to a treatment group (8 g/day of Valacyclovir) or control group (placebo). Treatment was initiated at the time of serological detection, and continued until amniocentesis. The primary endpoint was the rate of vertical transmission of CMV—determined by amniotic fluid CMV PCR. Secondary endpoints included evidence of symptomatic congenital CMV infection—in utero or postnatally.ResultsOne hundred women were recruited, 90 were included in the data analysis; 45 patients received Valacyclovir and 45 placebo. There were 2 twin pregnancies, and therefore 92 amniocentesis Amongst the Valacyclovir group, 5 (11.1%) amniocentesis were positive for CMV, compared with 14 (29.8%) in the placebo group (P GLMM = 0.03), corresponding with an odds ratio of 0.29 (95% CI: 0.09–0.90) for vertical CMV transmission. Amongst patients infected during the first trimester, a positive amniocentesis for CMV was significantly (P = 0.02) less likely in the Valacyclovir arm (2/19) compared with placebo (11/23). No significant differences (P = 0.91) in CMV-positive amniocentesis were observed between study arms amongst patients infected periconceptionally.ConclusionValacyclovir at a dose of 8 g/day is effective in reducing the rate of fetal CMV infection following early maternal primary infection during pregnancy. The drug reduces the rate of fetal infection by 71%.Disclosures All authors: No reported disclosures.

Recurrent maternal CMV infection associated with symptomatic congenital infection: results from a questionnaire study in Portugal

ObjectiveHuman cytomegalovirus (CMV) is the most widespread agent of congenital infection in humans and is still a challenging issue. Despite lower rates of vertical transmission being associated with recurrent infection...

Birth Prevalence of Congenital Cytomegalovirus (CMV) infection in a cohort of pregnant women in Bangladesh

Cytomegalovirus (CMV) is a frequent cause of congenital infection in humans in all regions of the world. In contrast to most congenital viral infections, congenital CMV infection and disease have been consistently demonstrated in populations with a high seroprevalence. Three hundred pregnant women were studied prospectively in their 1st, 2nd and 3rd trimester to determine the seroprevalence and seroconversion of CMV in pregnancy. After birth, babies were also tested for anti CMV IgM to determine the rate of birth prevalence. Anti CMV IgG and IgM tests were performed by chemiluminescence methods. All 300 (100%) pregnant women were anti CMV IgG positive and 180 (60%) were subsequently anti CMV IgM positive during different trimesters of pregnancy. Birth prevalence of CMV IgM antibody was 1.3% among babies of anti CMV IgM positive mothers whereas none in CMV IgM negative mothers (OR 1.01, 95% CI .996-1.027).It may be concluded that CMV IgG seroprevalence is high among Bangladeshi pregnant women and the rate of CMV reactivation is also high during pregnancy. Despite protection by maternal immunity a certain percent of babies acquire congenital CMV infection.

SAG5B and SAG5C combined vaccine protects mice against Toxoplasma gondii infection

Infections with the protozoan parasite Toxoplasma gondii, which are common around the world, can lead to congenital infections in humans. T. gondii surface antigen protein 5B (SAG5B) and SAG5C are potential stimulators of humoral and cellular immune responses. In this study, a multi-antigenic DNA vaccine constructed to express T. gondii SAG5B and SAG5C proteins simultaneously was used to immunize BALB/c mice to evaluate the protective efficacy of the vaccine. IgG antibody and gamma interferon (IFN-γ) cytokine production in the pSAG5B/SAG5C DNA vaccine group were significantly higher (0.853±0.103 and 915.2±106.9, respectively) than in the single DNA vaccine groups (pSAG5B, 0.667±0.109 and 598.3±74.9, respectively; pSAG5C, 0.696±0.092 and 623.7±95.5, respectively). After a lethal challenge with 1×104 RH strain tachyzoites, the survival time of the mice (17days) immunized with pSAG5B/SAG5C was longer than that of the single-gene-immunized mice (12days) or the control mice (6days). Moreover, after intragastric infection with 20 T. gondii PRU (low virulence) strain cysts, the number of brain cysts in the pSAG5B/SAG5C-vaccinated mice was only 25% of the number for the PBS-injected mice. Our findings indicate that, in comparison with the other mouse groups, the multi-antigenic DNA vaccine (pSAG5B/SAG5C) significantly induced immune responses and improved the protection against challenge with T. gondii in the host animals.

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression.

Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70). Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant. Indeed, ex vivo experiments showed that peritoneal macrophages pre-stimulated with rTgHSP70 presented increased NO production and enhanced parasite killing, and the protein was able to directly stimulate B cells toward antibody producing profile. In addition, rTgHSP70 immunization leads to high specific antibody titters systemically and a mixed IgG1/IgG2a response, with predominance of IgG1 production. Nonetheless, it was observed that the pretreatment of the parasite with rTgHSP70 immune sera was not able to control T. gondii internalization and replication by NIH fibroblast neither peritoneal murine macrophages, nor anti-rTgHSP70 antibodies were able to kill T. gondii by complement-mediated lysis, suggesting that these mechanisms are not crucial to resistance. Interestingly, when in combination with Alum, rTgHSP70 immunization was able to reduce inflammation in the brain of infected mice and in parallel anti-rTgHSP70 immune complexes in the serum. In conclusion, immunization with rTgHSP70 induces massive amounts of iNOS expression and reduced brain parasitism, suggesting that iNOS expression and consequently NO production in the brain is a protective mechanism induced by TgHSP70 immunization, therefore rTgHSP70 can be a good candidate for vaccine development against toxoplasmosis.

Characterising variation in five genetic loci of cytomegalovirus during treatment for congenital infection

Cytomegalovirus (CMV) is the most common congenital infection in humans and a leading cause of sensorineural hearing loss. Ganciclovir (6 mg/kg twice daily for 42 days) has been shown to reduce hearing deterioration and is used in clinical practice. Vaccines and passive administration of antibody are being evaluated in randomized controlled trials in allograft candidates, women of childbearing age, and pregnant women with primary CMV infection. To help define genetic variation in each of the targets of these therapeutic interventions, we amplified and sequenced genes UL97 (site utilised for ganciclovir phosphorylation), UL55 (glycoprotein B (gB) vaccine target) and UL128, UL130, and UL131a (specific monoclonal antibody targets). Serial blood, saliva, and urine samples (total 120) obtained from nine infants with symptomatic congenital CMV treated with 42 days' ganciclovir were analyzed. All samples tested were UL97 wild type at baseline and none developed mutations during treatment, showing no selection of resistance. The prevalences of UL55 genotypes were 28% gB1, 22% gB2, 1% gB3, and mixed in 20% samples. No mutations were noted in UL128-131a. Phylogenetic tree analysis showed that sequences with variations were found in multiple body sites of individual patients, so there was no evidence of body site compartmentalization of particular strains of CMV. The significance of these results for changes in diagnostic practices and therapeutic interventions against CMV are discussed. J. Med. Virol. 89:502-507, 2017. © 2016 Wiley Periodicals, Inc.

Disease watch: Zika virus - placental passage and permissivity for infection.

Animal models of human congenital infection are needed to understand when, how and why Zika virus (ZIKV) is transmitted to the fetus. The recent development of mouse models of ZIKV placental transmission, which results in high rates of pregnancy loss, alongside fetal brain and ocular malformations, have started to unravel the mysteries of placental infection and transmission.

Is Toxoplasma gondii type related to clinical outcome in human congenital infection? Systematic and critical review.

In human congenital toxoplasmosis the effects of parasite burden and pregnancy time at infection on clinical outcome are well known, but there is controversy regarding the role of Toxoplasma gondii type. Through a systematic review of the literature, we aimed to discern if T. gondii type has a role on clinical outcome in human congenital toxoplasmosis. We built up a database of congenital toxoplasmosis from reports of cases, case series and screening-based cohorts, which had information about parasite type, gestation time at maternal infection and/or clinical outcome in the product. Then, we obtained frequencies for loci used to genotype geographical origin of cases and types found. Also, odds ratios were calculated for association between time of maternal infection or parasite type on outcome. Type II parasites were the most common in Europe, Asia and Africa, while in America there were mainly atypical strains. More newborns with clinical problems were born from mothers infected during the first half of gestation than from those acquiring the parasite after week 24, regardless of parasite genotype (92.9 vs. 16.1%, OR = 67.9, CI95 25.4-181.6). Type I and atypical parasites were associated with clinical problems as opposed to types II and III, regardless of pregnancy period at infection (86.9 vs. 72.9%, OR = 2.47, CI95 1.1-5.4). A significant and remarkable tendency of type I parasites to be present during early pregnancy was also observed (94.4 vs. 5.6%, P < 0.009). In addition to parasite burden and period of gestation, T. gondii genotype seems involved in CT clinical outcome.

Evaluation of immune responses induced by rhoptry protein 5 and rhoptry protein 7 DNA vaccines against Toxoplasma gondii.

Infection with the protozoan parasite Toxoplasma gondii is widespread, and the organism can cause congenital infections in humans. The horizontal transmission of Toxoplasma is even more common than congenital. An effective vaccine strategy brings the prospect of improving Toxoplasma disease control. Rhoptry protein 5 (ROP5) and ROP7 are potential stimulators of humoral and cellular immune responses. In this study, we constructed a multi-antigenic DNA vaccine expressing ROP5 and ROP7 of T.gondii and compared the protective efficacy to single-gene vaccines and control groups. BALB/c mice were immunized intramuscularly three times. The levels of IgG antibodies and cytokines in mice immunized with the multi-antigenic DNA vaccine (pROP5/ROP7) were significantly higher than those in the control mice. Mice vaccinated with pROP5/ROP7 showed a longer survival time (16days) than single-gene-immunized mice (11 and 12days, respectively) or control mice (8days) after a challenge with 1×10(4) tachyzoites of RH strain of T.gondii. Furthermore, after intragastric infection with 20 cysts of PRU strain of T.gondii, the number of brain cysts in mice immunized with pROP5/ROP7 was only 25% of the number in control mice. Our results showed that a DNA vaccine encoding ROP5 and ROP7 significantly enhanced protection against T.gondii challenge.

Murine cytomegalovirus (CMV) infection via the intranasal route offers a robust model of immunity upon mucosal CMV infection.

Cytomegalovirus (CMV) is a ubiquitous virus, causing the most common congenital infection in humans, yet a vaccine against this virus is not available. Experimental studies of immunity against CMV in animal models of infection, such as the infection of mice with mouse CMV (MCMV), have relied mainly on parenteral infection protocols, although the virus naturally transmits by mucosal routes via body fluids. To characterize the biology of infections by mucosal routes, we compared the kinetics of virus replication, latent viral load and CD8 T-cell responses in lymphoid organs upon experimental intranasal (targeting the respiratory tract) and intragastric (targeting the digestive tract) infection with systemic intraperitoneal infection of two unrelated mouse strains. We observed that intranasal infection induced robust and long-term virus replication in the lungs and salivary glands but limited replication in the spleen. CD8 T-cell responses were somewhat weaker than upon intraperitoneal infection but showed similar kinetic profiles and phenotypes of antigen-specific cells. In contrast, intragastric infection resulted in abortive or poor virus replication in all tested organs and poor T-cell responses to the virus, especially at late times after infection. Consistent with the T-cell kinetics, the MCMV latent load was high in the lungs but low in the spleen of intranasally infected mice and lowest in all tested organs upon intragastric infection. In conclusion, we showed that intranasal but not intragastric infection of mice with MCMV represents a robust model to study the short- and long-term biology of CMV infection by a mucosal route.

The Seropositivity of Toxocara spp. Antibodies in Pregnant Women Attented at the University Hospital in Southern Brazil and the Factors Associated with Infection.

BackgroundHuman toxocariasis is a parasitic zoonosis with a worldwide distribution but is underdiagnosed with an underestimated impact on human health. The ingestion of embryonated eggs of Toxocara spp. present on the hands or in contaminated food or water is the main mode of infection. The only record of Toxocara congenital infection in humans occurred in a premature infant. Helminth infections during pregnancy may be associated with reproductive disorders. Studies investigating the occurrence of toxocariasis in pregnancy are scarce, as is research on the possible implications of these parasites in reproductive health. The aim of this study was to determine the seroprevalence of antibodies to Toxocara spp. in pregnant women and to identify risk factors associated with its infection.Methodology/Principal FindingsThe cross-sectional study of the seropositivity of specific antibodies for Toxocara spp. was performed on 280 pregnant women. Serum samples were examined with enzyme-linked immunoassay. Epidemiological data were obtained through a questionnaire containing information about obstetric history, general life style choices, and the social and economic status of the women. The prevalence of Toxocara spp. IgG in pregnant women was 6.4%. Some of the risk factors associated with the infection were owning dogs (p = 0.003), living in the city centre (p = 0.028), living at the city beach (p = 0.003), and having a family income at or below minimum wage (p < 0.001). There was no association between reproductive disorders and Toxocara seropositivity.Conclusions/SignificanceThe seroprevalence of 6.4% for Toxocara spp. in pregnant women shows that there was exposure to the parasite. The study demonstrates the need for attention for the completion of clinical diagnosis parameters, as well as the expansion of highly specific serological studies in different regions to understand the impact of toxocariasis in pregnancy.

A neutralizing anti-gH/gL monoclonal antibody is protective in the guinea pig model of congenital CMV infection.

Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2–1% of all births, and causes birth defects and developmental abnormalities, including sensorineural hearing loss and developmental delay. Several key studies have established the guinea pig as a tractable model for the study of congenital HCMV infection and have shown that polyclonal antibodies can be protective [1]–[3]. In this study, we demonstrate that an anti-guinea pig CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody protects against fetal infection and loss in the guinea pig. Furthermore, we have delineated the kinetics of GPCMV congenital infection, from maternal infection (salivary glands, seroconversion, placenta) to fetal infection (fetus and amniotic fluid). Our studies support the hypothesis that a neutralizing monoclonal antibody targeting an envelope GPCMV glycoprotein can protect the fetus from infection and may shed light on the therapeutic intervention of HCMV congenital infection in humans.