Challenging diagnosis of congenital malaria in non-endemic areas.

BACKGROUND: Congenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported. CASE PRESENTATION: A 2-month-old male child was admitted to Bambino Gesù Children's Hospital due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34 weeks' gestation after a bicorial, biamniotic pregnancy by a migrant woman from Nigeria. He was the first of non-identical twins. Combined with anaemia, spleen and liver enlargement was noted, malaria was hypothesized. Malaria laboratory panel was performed on the newborn, mother and other twin blood samples, as follows: (i) malaria rapid diagnostic test (RDT); (ii) Giemsa-stained thick and thin blood smears for Plasmodium spp. identification and parasitaemia titration; (iii) molecular screening and typing of Plasmodium spp. by multiplex qualitative PCR assay based on 18S rRNA gene. Genotyping of Plasmodium falciparum isolates from mother and child was performed by neutral microsatellite and highly polymorphic marker amplification. CONCLUSIONS: The maternal RDT sample was negative, while the infant RDT was positive; in both cases microscopy of blood smears and PCR showed infection with P. falciparum. Two of the genotypic molecular markers displayed different allelic variants between the two samples. This difference could imply infection multiplicity of the mother during the pregnancy, possibly harbouring more than one isolate, only one of them being transmitted to the newborn while the other persisting in the mother's blood. Because of the increasing number of pregnant women coming from endemic areas for malaria, an accurate anamnesis of infant's mother, and the inclusion of Plasmodium spp. research into TORCH screenings for mother-infant pair at birth, aiming at reducing morbidity and mortality associated to the disease might be suitable.

Ocular manifestation of congenital toxoplasmosis, clinical implication - case report.

The aim of this case report was to present extremely severe, ophthalmic complications in form of rare, congenital toxoplasmatic bilateral defect of eye-balls concomitant with advanced uveitis, microphthalmia and eye-multistructural developmental abnormalities leading to irreversible visual disability. The ocular diagnosis was confirmed in Ret-Cam II and ultrasonography and it was accompanied with congenital multiorgan lesions including hepato-splenomegaly, thrombocytopenia, leukomalacia, hydrocephalus and ventriculomegaly with neurological symptoms. Serology, PCR of cerebro-spinal fluid and cord blood confirmed the presence of congenital Toxoplasma gondii infection in the infant. The authors took the effort of insightful analysis for the causes of applied treatment failure in mother during pregnancy, analyzing the inefficacy of Spiromycin therapy in pregnant woman and evaluating false-negative result of amniocentesis for Toxoplasma gondii presence. Among many issues concerning anti-toxoplasmatic treatment in mother and infant presented in this article, the need for multiple repetition of toxoplasmatic tests should be underlined including amniotic fluid PCR and ultrasonography which can add much important data for correct diagnosis. The authors indicate that the lack of benefits from conservative therapy in case of suspected Toxopalsma gondii suggestion lead to dramatic multiorgan complications, especially ophthalmo-neurologic, leading to irreversible visual disability.

Pregnancy-associated malaria and malaria in infants: an old problem with present consequences.

Albeit pregnancy-associated malaria (PAM) poses a potential risk for over 125 million women each year, an accurate review assessing the impact on malaria in infants has yet to be conducted. In addition to an effect on low birth weight (LBW) and prematurity, PAM determines foetal exposure to Plasmodium falciparum in utero and is correlated to congenital malaria and early development of clinical episodes during infancy. This interaction plausibly results from an ongoing immune tolerance process to antigens in utero, however, a complete explanation of this immune process remains a question for further research, as does the precise role of protective maternal antibodies. Preventive interventions against PAM modify foetal exposure to P. falciparum in utero, and have thus an effect on perinatal malaria outcomes. Effective intermittent preventive treatment in pregnancy (IPTp) diminishes placental malaria (PM) and its subsequent malaria-associated morbidity. However, emerging resistance to sulphadoxine-pyrimethamine (SP) is currently hindering the efficacy of IPTp regimes and the efficacy of alternative strategies, such as intermittent screening and treatment (IST), has not been accurately evaluated in different transmission settings. Due to the increased risk of clinical malaria for offspring of malaria infected mothers, PAM preventive interventions should ideally start during the preconceptual period. Innovative research examining the effect of PAM on the neurocognitive development of the infant, as well as examining the potential influence of HLA-G polymorphisms on malaria symptoms, is urged to contribute to a better understanding of PAM and infant health.

Neospora caninum NC-6 Argentina induces fetopathy in both serologically positive and negative experimentally inoculated pregnant dams.

Neospora caninum infection is a major cause of abortion in cattle. The objectives of this study were to genetically characterize the N. caninum NC-6 Argentina isolate using a multilocus microsatellite analysis approach and to study its biological behavior by experimental inoculations into seronegative and seropositive pregnant cattle, evaluating the humoral and cellular immune response elicited and the occurrence of transplacental transmission and fetopathy. Pregnant cows (65 days of gestation) seropositive and seronegative to N. caninum were intravenously inoculated with tachyzoites of the NC-6 Argentina N. caninum strain and slaughtered at 108 ± 2 days of gestation. Serum samples were analyzed for N. caninum antibodies by indirect fluorescent antibody test. The cellular immune response was analyzed by detection of gamma interferon (γIFN) production in blood cells. Tissue samples from dams, fetuses, and placental cotyledons were processed by histopathological and immunohistochemical techniques and examined for N. caninum DNA by PCR. Positive DNA samples were further analyzed by multilocus microsatellite typing for N. caninum. Inoculated animals had significantly higher N. caninum antibody titers and γIFN production than control animals. One seropositive inoculated cow aborted, one seronegative cow had a non-viable fetus, and the remaining fetuses from the experimentally inoculated dams had histopathologic lesions. The PCR was positive in 3/4 fetuses from seronegative inoculated cows and in 2/3 fetuses from seropositive inoculated cows. Multilocus microsatellite analysis revealed that the N. caninum DNA present in fetuses and placentas had an identical pattern to NC-6 Argentina strain. The NC-6 Argentina strain proved to be able to cross the placenta and to induce fetopathy in both the seropositive and seronegative dams.

Congenital toxoplasmosis presenting with fetal atrial flutter after maternal ingestion of infected moose meat.

Consumption of undercooked game meat during pregnancy is considered a risk factor for congenital toxoplasmosis, but cases definitively linking ingestion of infected meat to clinical disease are lacking. We report a confirmed case of congenital toxoplasmosis identified because of atrial flutter in the fetus and linked to maternal consumption of Toxoplasma gondii PCR-positive moose meat.

Toxoplasma gondii SAG2, SAG3 and GRA6 alleles and single nucleotide polymorphism in congenital infections with known parasite load and clinical outcome.

Amniotic fluid DNA samples were genotyped by multilocus-nested-PCR-RFLP, but only three of 11 markers amplified 113 of 122 (92.6%) samples, resulting in 12 untyped and 101 partial non-archetypal genotypes. The 101 typed samples were subdivided into four groups: G1 with 73 samples (5'and 3' SAG2 allele I + SAG3 allele III + GRA6 allele III), 53 had parasite load ≤ 102 parasites/mL (43 asymptomatic, 10 mild infections), 17 had load > 102 and ≤ 103 (one mild, 13 moderate and three severe), and three had load > 103 parasites/mL (three severe); G2 with 22 samples (5'and 3' SAG2 allele I + SAG3 allele III), all parasite load levels ≤ 102 parasites/mL (18 asymptomatic and four mild); G3 with five samples (5' and 3' SAG2 allele I + SAG3 allele II), parasite load ≤ 102 parasites/mL (three asymptomatic and two mild); G4 with one sample (5' and 3' SAG2 allele II + SAG3 allele II + GRA6 allele I), a parasite load < 102 parasites/mL in an asymptomatic infant. After DNA sequencing, restriction sites confirmed SAG2, SAG3 and GRA6 alleles in 98.7%, 100% and 100% of the cases, respectively, while single nucleotide polymorphisms confirmed 90% of 5'-SAG2 allele I; 98.7% of 3'-SAG2 allele I; 98% of SAG-3 allele III, but only 40% of GRA6 allele III results. For the moment, partial non-archetypal genotypes of parasites did not show any relationship with either parasite load in amniotic fluid samples or clinical outcome of infants at the age of 12 months.

The effects of malaria and intermittent preventive treatment during pregnancy on fetal anemia in Malawi.

BACKGROUND: Fetal anemia is common in malarious areas and is a risk factor for infant morbidity and mortality. Malaria during pregnancy may cause decreased cord hemoglobin (Hb) and fetal anemia among newborns. Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is protective against malaria but may also affect hematopoiesis and contribute to fetal anemia. METHODS: Peripheral, placental, and cord blood were examined for malaria parasitemia and Hb concentration in a cross-section of 3848 mothers and infants delivered at Queen Elizabeth Central Hospital in Blantyre, Malawi between 1997 and 2006. Unconditional linear and logistic regressions were performed with multiple imputation for missing covariates to assess the associations between malaria, IPTp with SP, and fetal anemia. RESULTS: The overall prevalence of fetal anemia was 7.9% (n = 304). Malaria parasitemia at delivery was associated with an adjusted decrease in cord Hb of -0.24 g/dL (95% confidence interval [CI], -.42 to -.05). The adjusted prevalence odds ratio for the effect of malaria on fetal anemia was 1.41 (95% CI, 1.05-1.90). Primigravidae who did not take IPTp had infants at highest risk for fetal anemia, and density of parasitemia was correlated with the decrease in cord Hb. There was no significant association between SP use and cord Hb or fetal anemia. CONCLUSIONS: Malaria during pregnancy, but not IPTp, decreases cord Hb and is a risk factor for fetal anemia in Malawi. Intermittent preventive treatment during pregnancy with SP may continue to be safe and effective in preventing malaria during pregnancy and fetal anemia despite development of SP resistance.

[Effect of congenital infection by Trypanosoma cruzi on intrauterine development and the fetal-neonatal immune response]. / Efecto de la infección congénita por Trypanosoma cruzi sobre el desarrollo intrauterino y la respuesta inmune fetal-neonatal.

In congenital infection by Trypanosoma cruzi, morbidity and mortality vary from asymptomatic cases to severe clinical forms of the disease. It has been found that there is no specific clinical profile in newborns infected by T. cruzi, since during intrauterine development diverse pathological changes take place, causing alterations in the serological and parasitological profiles. Some intrinsic factors of the host, such as: the placental barrier and the ability of both, mother and fetus, to develop a specific immune response to control parasite multiplication, could be involved in such differences. Another possibility includes the genetic polymorphism of T. cruzi, since it is considered that strains of greater virulence can cross the placenta more easily and are more pathogenic to the fetus and/or the neonate.

Infections at the maternal-fetal interface: an overview of pathogenesis and defence.

Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym 'TORCH' (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission.

Maternal Schistosomiasis japonica is associated with maternal, placental, and fetal inflammation.

Schistosomes infect ∼40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial in Schistosoma mansoni did not detect this association. We conducted an observational study among 99 pregnant women living in an area of Schistosoma japonicum endemicity in the Philippines. We enrolled women at 32 weeks gestation and measured S. japonicum and geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1ß), and cord (IL-1ß and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1ß, and TNF-α production by syncytiotrophoblasts was independently associated with decreased birth weight (both P < 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth.

Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP3(+) Treg and more generalized FOXP3(+) CD4(+) Treg in chronic and resolved PM, alongside increased Th1 pro-inflammatory responses (IFN-gamma, TNF-alpha, IFN-gamma:IL-10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.

Evidence of congenital transmission of Neospora caninum in naturally infected water buffalo (Bubalus bubalis) fetus from Brazil.

The aim of this study was to determine the congenital infection by Neospora caninum in the water buffalo (Bubalus bubalis), a natural intermediate host. Nine pregnant water buffalos, raised under free-grazing condition, were slaughtered, and their fetuses were collected. Samples of brain and thoracic fluid were obtained from those fetuses, with gestational ages ranging from 2 to 5 months. The DNA of N. caninum was detected and identified in the brain of one of those fetuses, using two PCR assays, one directed to the Nc5 gene and the other, to the common toxoplasmatiid ITS1 sequence. The DNA fragments produced on PCR were sequenced, and N. caninum was confirmed in the samples. No antibodies to N. caninum were detected on any sample of thoracic fluid by immunofluorescent antibody test (IFAT < 25). This is the first confirmation of congenital transmission of N. caninum in water buffalos.

[Cases of Toxoplasma gondii infection in foetus's and toxoplasmic encephalitis in immunosupressed patients confirmed by PCR method in NIPH - NIH, 2009-2010]. / Potwierdzenie przypadków toksoplazmozy plodu oraz toksoplazmozy centralnego ukladu nerwowego za pomoca metody PCR w badaniach wykonanych w NIZP-PZH w latach 2009-2010.

The results of molecular tests for Toxoplasma gondii infection carried out in NIPH-NIH were presented in the light of current data on diagnostics and epidemiology of toxoplasmosis. Between January 2009 and December 2010 four cases of active toxoplasmosis were confirmed using PCR targeting the 529-bp repeat element of Toxoplasma gondii. Intrauterine infection was found in 3 out of 180 (1.7%) examined women. Toxoplasmic encephalitis was confirmed in one patient who was a liver transplant recipient. T. gondii was not detected in cerebrospinal fluid of 19 out of 20 examined patients with encephalitis. The cases of intrauterine toxoplasmosis diagnosed in 2009-2010 make 57.1% of all cases diagnosed in the last decade. In 2001-2010 toxoplasmic encephalitis was detected in two patients out of 45 examined. The choice of tests and interpretation of the results are important elements of T. gondii infection diagnosis and require cooperation between clinicians and laboratory diagnosticians. Establishing reference center for toxoplasmosis in Poland would contribute towards the improvement of standards of diagnostics and treatment of cases of congenital infections and the infection in immunosuppresed patients.

Early onset of clinical leishmaniosis in a litter of pups with evidence of in utero transmission.

BACKGROUND: Canine leishmaniosis (CanL) is a zoonotic disease caused by Leishmania infantum. Although usually transmitted by phlebotomine sand flies, infection by vertical transmission and by blood transfusion have also been reported. METHODS: We describe the very early onset of clinical leishmaniosis, starting from 2 months of age, in a litter of pups born to an infected dam and sire. Seven pups from the litter of nine living in different households showed alopecic, exfoliative dermatitis and ulcerative cutaneous lesions. All pups and both parents were tested on at least one occasion both serologically, by enzyme-linked immunosorbent assay (ELISA), and by polymerase chain reaction (PCR) targeting the Leishmania ribosomal operon internal transcribed spacer 1 region and a short fragment of the kinetoplast minicircle; positive amplicons were sequenced. RESULTS: All nine pups were PCR positive for L. infantum verified by DNA sequencing, seven were positive by conjunctival, five by blood, four by lymph node, and one by skin PCR from an ulcerative lesion. Both pups with no clinical signs were seronegative, while five of the seven pups with dermatologic abnormalities were seropositive by ELISA. The sire had typical clinical dermatologic and visceral findings of CanL, was seropositive and PCR positive for L. infantum in the lymph node and fluid from the vas deferens tested after the testes were removed by castration. The dam was sub-clinically infected and seronegative, but positive by blood, lymph node and conjunctival PCR for L. infantum. Allopurinol administered to all clinically affected dogs resulted in clinical recovery. CONCLUSIONS: Infection with L. infantum in both parents, the very early age of clinical onset among most of the pups, and the fact that the puppies were born and detected with signs of leishmaniosis in the winter, which is a season without sand fly activity in Israel, strongly suggest vertical transmission. Awareness of the possibility of vertical transmission of L. infantum and infection in littermates should be increased. It is recommended that littermates of young dogs with clinical leishmaniosis should be tested for sub-clinical infection as they may also be infectious to sand flies and thus to other dogs and to humans. Restricting the mating of infected bitches should also be considered to prevent the vertical transmission of the infection.

Fetal Cytokine Balance, Erythropoietin and Thalassemia but Not Placental Malaria Contribute to Fetal Anemia Risk in Tanzania.

Fetal anemia is common in malaria-endemic areas and a risk factor for anemia as well as mortality during infancy. Placental malaria (PM) and red cell abnormalities have been proposed as possible etiologies, but the relationship between PM and fetal anemia has varied in earlier studies, and the role of red cell abnormalities has not been studied in malaria-endemic areas. In a Tanzanian birth cohort study designed to elucidate the pathogenesis of severe malaria in young infants, we performed a cross-sectional analysis of risk factors for fetal anemia. We determined PM status, newborn red cell abnormalities, and maternal and cord blood levels of iron regulatory proteins, erythropoietin (EPO), cytokines and cytokine receptors. We examined the relationship between these factors and fetal anemia. Fetal anemia was present in 46.2% of the neonates but was not related to PM. Maternal iron deficiency was common (81.6%), most frequent in multigravidae, and interacted with parity to modify risk of fetal anemia, but it was not directly related to risk. Among offspring of iron-deficient women, the odds of fetal anemia increased with fetal α+-thalassemia, as well as these patterns of cord blood cytokines: increased cord IL-6, decreased TNF-RI, and decreased sTfR. The EPO response to fetal anemia was low or absent and EPO levels were significantly decreased in newborns with the most severe anemia. This study from an area of high malaria transmission provides evidence that 1) fetal α+-thalassemia and cytokine balance, but not PM at delivery, are related to fetal anemia; 2) maternal iron deficiency increases the risk that other factors may cause fetal anemia; and 3) fetal anemia has a multifactorial etiology that may require a variety of interventions, although measures that reduce maternal iron deficiency may be generally beneficial.

Toxoplasmosis screening during pregnancy in France: Opinion of an expert panel for the CNGOF.

Prenatal screening to prevent congenital toxoplasmosis as performed in France for several decades has been questioned in view of the decreasing incidence of this infection and the cost of testing. The French College of Obstetrics and Gynecology mandated a multidisciplinary panel of experts to perform a reassessment of the screening program in accordance with international good practice. In France, about 70% of pregnant women are not immune to T. gondii, and 0.2-0.25% become infected during pregnancy. The risk of maternal-fetal transmission of infection is on average 25-29% and depends greatly on the gestational age at seroconversion. In case of fetal transmission, the outcome is livebirth in 95% of cases, with latent congenital toxoplasmosis in 90% of cases and symptomatic forms in 10% of cases, of which 1/3 are severe and 2/3 moderate. Biological techniques have satisfactory performance regarding serologies for the diagnosis of maternal infections and PCR on amniotic fluid for the prenatal diagnosis of congenital toxoplasmosis. Primary prevention of toxoplasmosis is based on hygiene measures that are relatively simple, but poorly implemented. In case of maternal seroconversion, there is a strong case for prenatal prophylactic treatment as soon as possible (ideally within 3 weeks of seroconversion), spiramycin before 14 weeks of gestation (WG), and with a tendency to superiority of the pyrimethamine/sulfadiazine association over spiramycin beyond 14 W G, in order to reduce the risk of symptomatic congenital toxoplasmosis. In case of congenital toxoplasmosis, prompt initiation of treatment reduces the occurrence of cerebral signs and symptoms, as well as retinal lesions. Several medico-economic evaluations of the French toxoplasmosis screening program have been conducted including an individual cost-effectiveness approach with decision analysis which concluded on the profitability of prenatal screening as carried out in France (monthly surveillance of seronegative women, prenatal treatment in case of seroconversion, termination of pregnancy in severe forms). Though most international societies do not recommend systematic screening for mainly financial reasons, if congenital toxoplasmosis appears benign in France today, it is probably thanks to screening and the possibility of early treatment of fetuses and/or newborns. Thus, the panel recommends continuing for now the program in France for prevention of congenital toxoplasmosis.

[Detection of Trypanosoma cruzi DNA in the placenta and fetuses of mice with Chagasic acute infection]. / Detección de ADN de Trypanosoma cruzi en la placenta y fetos de ratones con infección chagásica aguda.

The objective of the present study was to detect the presence of Trypanosoma cruzi DNA in the placenta and fetal tissues of NMRI mice (Mus musculus) inoculated with 22 x 10(3) trypomastigotes metacyclic of the M/HOM/BRA/53/Y strain by intraperitoneal route. Mice were pregnant in the acute phase of the infection. The course of patent parasitemia by T. cruzi was evaluated before mating and during pregnancy. At day twenty of gestation, animals were sacrificed and the fetuses and their placentas were removed to evaluate T. cruzi infection. Samples of fetal placenta, heart and skeletal muscle were fixed in 10%, formalin, included in paraffin and stained with hematoxilin and eosin (HE). The histopathological study of sections of fetal tissues revealed inflammatory infiltrates with mononuclear and polymorphonuclear cells and without parasitism in these tissues. The amplification of T. cruzi DNA by Polymerase Chain Reaction (PCR) showed a positive reaction in 18% of placental tissue of pregnant infected mice. The samples of heart and skeletal muscle of the fetuses of mothers infected with T. cruzi did not show the presence T. cruzi DNA. The placenta and skeletal muscle of the fetuses analyzed by Peroxidase anti Peroxidase inmunostaining showed T. cruzi antigens in those tissues. Negative results by PCR in fetal tissues might be related with the virulence and tropism associated with the biological and genetic characteristic Of the T. cruzi strain used in the experimental infection of female mice.

Differential expression of genes in fetal brain as a consequence of maternal protein deficiency and nematode infection.

Maternal dietary protein deficiency and gastrointestinal nematode infection during early pregnancy have negative impacts on both maternal placental gene expression and fetal growth in the mouse. Here we used next-generation RNA sequencing to test our hypothesis that maternal protein deficiency and/or nematode infection also alter the expression of genes in the developing fetal brain. Outbred pregnant CD1 mice were used in a 2×2 design with two levels of dietary protein (24% versus 6%) and two levels of infection (repeated sham versus Heligmosomoides bakeri beginning at gestation day 5). Pregnant dams were euthanized on gestation day 18 to harvest the whole fetal brain. Four fetal brains from each treatment group were analyzed using RNA Hi-Seq sequencing and the differential expression of genes was determined by the edgeR package using NetworkAnalyst. In response to maternal H. bakeri infection, 96 genes (88 up-regulated and eight down-regulated) were differentially expressed in the fetal brain. Differentially expressed genes were involved in metabolic processes, developmental processes and the immune system according to the PANTHER classification system. Among the important biological functions identified, several up-regulated genes have known neurological functions including neuro-development (Gdf15, Ing4), neural differentiation (miRNA let-7), synaptic plasticity (via suppression of NF-κß), neuro-inflammation (S100A8, S100A9) and glucose metabolism (Tnnt1, Atf3). However, in response to maternal protein deficiency, brain-specific serine protease (Prss22) was the only up-regulated gene and only one gene (Dynlt1a) responded to the interaction of maternal nematode infection and protein deficiency. In conclusion, maternal exposure to GI nematode infection from day 5 to 18 of pregnancy may influence developmental programming of the fetal brain.

Toxoplasma gondii infection in horses. A review.

This review updates those written by Dubey and Beattie in 1988 (1988a) and by Tenter et al in 2000, on pathological and epidemiological aspects of Toxoplasma infection in horses. Under natural conditions, seroprevalence may variate from 0% up to 90%. This wide variation may be due to the sensitivity of the serological methods, to the age of animals, to the geographical area, and even to the hygienic condition of the farms and farm management. With few exceptions, horses are considered one of the less sensitive specie to the pathogenic effect of Toxoplasma gondii. In fact, neither under experimental nor under natural condition a genuine pathologic picture related to the toxoplasmic infection has been described. In one occasion the organism has been isolated from an eye condition and in others a connection between a higher frequency of unspecified pathological conditions and a positive response to serological test for Toxoplasma has been speculated. Diaplacental transmission and the following abortion have been only occasionally reported, and at least in one case in a quite trustworthy way, therefore it must be considered possible, though rare. Although infection of humans due to the consumption of horse meat has never been reported, the existence of a possible risk arouses by the demonstration of the presence of parasite stages in either naturally or experimentally infected horses, which resulted to be infective for mice and/or cats.