Maternal Anti-Toxoplasma Treatment during Pregnancy Is Associated with Reduced Sensitivity of Diagnostic Tests for Congenital Infection in the Neonate.

Neonatal diagnosis of congenital toxoplasmosis is based on a combination of serological and molecular tests. Maternal screening and treatment differ according to national policies and may impact the sensitivity of diagnostic methods in infants at birth. In this multicenter study, 115 neonates born to 61 treated (53%) and 54 (47%) untreated women were retrospectively included in three centers (France, Serbia, and the United States) to assess the impact of maternal anti-Toxoplasma treatment on the performance of neonatal workup at birth (neosynthesized anti-Toxoplasma IgM, IgA, and IgG and quantitative PCR [qPCR]) using univariate and multivariate approaches. Independently of the time of maternal seroconversion, the serological techniques were impacted differently by maternal treatment. The detection of IgM by immunosorbent agglutination assay (ISAGA) and Western blotting (WB) dropped from 90.7% and 88.2% in untreated neonates to 53.3% and 51.9% in treated neonates (P < 0.05), whereas IgM enzyme-linked immunosorbent assay (ELISA) and IgA ISAGA were not significantly affected by maternal treatment. A 2-fold reduction in the sensitivity of neosynthesized IgG by WB was also observed in the case of treatment during pregnancy (37.7% versus 82.3%). Interestingly, the effect of treatment was shown to be duration dependent, especially for IgM detection, when the treatment course exceeded 8 weeks, whatever the therapy. The sensitivity of Toxoplasma PCR in blood was also lowered by maternal treatment from 39.1% to 23.2%. These results highlight that anti-Toxoplasma therapy during pregnancy may set back biological evidence of neonatal infection at birth and underline the need for a careful serological follow-up of infants with normal workup.

Toxoplasmosis in Transplant Recipients, Europe, 2010-2014.

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management.

SARS-CoV-2 specific antibody response after an mRNA vaccine as the third dose: Homologous versus heterologous boost.

The aim of this study was to evaluate immunogenicity and longevity of the humoral immune response within six months after the homologous (BNT162b2/BNT162b2) or heterologous (BBIBP-CorV/BNT162b2) third dose, and to assess breakthrough infections among vaccinees during the Omicron wave in Serbia. Serum samples were analyzed at four timepoints: five months after the primary series; three weeks, three months, and six months after the boost. IgG antibodies against the receptor-binding domain of the spike protein were detected using enzyme-linked fluorescence assay. Both homologous (n = 55) and heterologous group (n = 36) showed a highly significant increase in antibody concentrations (p < 0.001) three weeks after the boost. A moderate inverse correlation between the age of recipients and the antibody levels at three weeks post-boost was observed in the homologous group (p = 0.02, r = -0.37), while the same correlation was not significant for heterologous group (p = 0.55, r = -0.15). Heterologous group had significantly higher antibody concentrations than homologous group at three weeks (Median 851.4(IQR 766.6-894.1); 784.3(676.9-847.4); p = 0.03) and three months post-boost (766.6(534.8-798.9); 496.8(361.6-664.0); p < 0.001). However, a significant decline in antibody response over time was noted for both strategies. The overall incidence of breakthrough cases was estimated at 36.36% (20/55) for homologous, and 16.67% (6/36) for heterologous group, but none of them required hospitalization. Although observed incidence in the homologous group was more than double when compared to the heterologous group, this difference was not statistically significant, most likely due to the small sample size. In conclusion, waning immunity after inactivated vaccine can be recovered by BNT162b2 heterologous boost regardless of the age of recipients, and both boost strategies induced potent humoral immune response and protection against severe COVID-19 during the Omicron wave. However, as the observed incidence of breakthrough infections was higher in the homologous group, although non-significant, this finding could indicate an advantage of heterologous approach.

Human infections by Hymenolepis diminuta in Europe: a case report and literature review.

We performed a review of published and gray literature of human Hymenolepis diminuta cases across Europe up to July 2022. Of all detectable publications and records, we further analyzed only those that contained demographic, clinical or epidemiological data regarding the infected subjects. Additionally, one case of hymenolepiasis in a 16-mo-old boy living in the urban part of Belgrade was included in the analysis. Published studies were based in 13/50 European countries and identified 104 laboratory-confirmed cases in total. Almost one-half (49%) of all cases originated from Mediterranean countries. Among symptomatic children, the infection most often manifested with diarrhea, abdominal pain, allergic reaction and behavioral changes. The diagnosis was made by the detection and identification of H. diminuta eggs or parts of strobila in stool samples, although cases of misdiagnosis were also reported. The parasite clearance was established with praziquantel or niclosamide, while the administration of albendazole or mebendazole led to unfavorable results. Future multicentric prospective studies focused on infection screening and the gathering of detailed sociodemographic and clinical data could provide an updated insight into the true distribution and characteristics of H. diminuta infection across Europe.

Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency.

In immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk.

Factors Associated with Toxoplasma gondii Seroprevalence in Pregnant Women: A Cross-Sectional Study in Belgrade, Serbia.

Toxoplasmosis, caused by the cosmopolitan protozoan Toxoplasma gondii, has particular implications during pregnancy due to the possible transmission of infection to the fetus. Very few studies have assessed seroprevalence and the risk factors for toxoplasmosis in healthy pregnant women. The aim of this study was to examine the seroprevalence of T. gondii infection in healthy pregnant women and to identify the associated risk factors for toxoplasmosis. The cross-sectional study involved 300 healthy pregnant women who came to the Institute for Blood Transfusion in Belgrade between November 2018 and February 2019 for routine blood group and Rh factor testing before delivery, who were also tested using serological screening for the presence of specific antibodies. Positives were further examined using enzyme immunoassay. Of the total sera of participants analyzed, 38 were positive for specific IgG, resulting in a seroprevalence rate of 12.7% (95% Confidence Interval (CI) 9.1-17.0%). All pregnant women presented negative anti-T. gondii IgM antibodies. The multivariate logistic regression analysis revealed that living in a house with a garden was independently associated with the risk of T. gondii infections, while eating chicken meat was connected with a lower risk compared to eating other types of meat with an odds ratio (OR) of 2.5 (95% CI 1.21-5.02) and an OR of 0.3 (95% CI 0.09-0.83), respectively. Although the prevalence of anti-T. gondii IgG antibodies is relatively low, it is essential to maintain and adapt evidence-based preventive measures for toxoplasmosis continually.

New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features.

Herein, upgraded chloroquine (CQ) derivatives capable of overcoming Plasmodium resistance and, at the same time, suppressing excessive immune response and risk of concurrent bacteremia were developed. Twelve new ferrocene-CQ hybrids tethered with a small azathia heterocycle (1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, or 5-methyl-1,3-thiazolidin-4-one) were synthesized and fully characterized. All hybrids were evaluated for their in vitro antiplasmodial, antimicrobial, and immunomodulatory activities. Additional assays were performed on selected hybrids to gain insights into their mode of action. Although only hybrid 4a was more potent than the parent drug toward CQ-resistant Dd2 Plasmodium falciparum strain, several other hybrids (such as 6b, 6c, and 6d) manifested substantially improved antimicrobial and immunomodulatory properties. Interesting structure-activity relationship data were obtained, hinting at future research for the development of new multitarget chemotherapies for malaria and other infectious diseases complicated by drug resistance, bacterial co-infection, and immune-driven pathology issues.

Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis.

OBJECTIVES: Reactivation of latent toxoplasmosis may be life-threatening in haematopoietic stem cell transplant (HSCT) recipients. We conducted an 8-year-long prospective study on the diagnosis and monitoring of reactivated toxoplasmosis in paediatric HSCT recipients. The primary objective was to determine the incidence of reactivated toxoplasmosis in a setting that withholds prophylaxis until engraftment. The second objective was to identify the subgroups of HSCT recipients particularly prone to reactivation who may benefit the most from regular PCR follow-up. METHODS: Serological and qPCR screening targeting the Toxoplasma 529 bp gene was performed before HSCT, and continued by weekly monitoring after HSCT for a median time of 104 days. RESULTS: Reactivated toxoplasmosis was diagnosed in 21/104 (20.2%), predominantly in allo- (19/75) and rarely in auto-HSCT (2/29) recipients. Over 50% (14/21) of cases were diagnosed during the first month after HSCT, while awaiting engraftment without prophylaxis. Toxoplasma disease evolved in only three (14.3%, 3/21) patients, all treated by allo-HSCT. Reactivation was more frequent in patients treated for acute lymphoblastic leukaemia (3/27, p 0.03) and especially, in recipients of haploidentical stem cells (10/20, p 0.005). Seronegative status of the donor (where was known) contributed to 75% (12/16) cases of reactivated toxoplasmosis after allo-HSCT. DISCUSSION: The presented results show that peripheral blood-based qPCR, both before and after HSCT, is a valuable asset for the diagnosis of reactivated toxoplasmosis, whereas the results of serology in recipients should be interpreted with caution. Weekly qPCR monitoring, at least until successful engraftment and administration of prophylaxis, allows for prompt introduction of specific treatment.

Epidemiology of Toxoplasmosis in SERBIA: A Cross-Sectional Study on Blood Donors.

Toxoplasmosis is a globally distributed parasitic zoonosis, affecting approximately one third of the human population. Epidemiological studies on toxoplasmosis conducted in Serbia so far have been focused on women of childbearing age, without a clear insight into the prevalence in the general population. We conducted a cross-sectional study in a representative sample of the healthy adult population consisting of 1095 blood donors of both genders to establish the prevalence and risk factors for Toxoplasma gondii infection. Data on the demographic and clinical characteristics of all study participants, as well as on their lifestyle habits, were collected by means of a questionnaire. The overall prevalence of infection was 20.5% (224/1095) and the avidity of the specific IgG antibodies detected was high in a vast majority of the seropositive donors (98.2%). Interestingly, the remaining 1.8% of the specific IgG positive samples were of borderline avidity (4/224), in complete absence of specific IgM. The multivariate logistic regression analysis showed that independent risk factors included age (from OR (95% CI) 1.9 (1.13−3.28) in the 30−39 age group, to 6.8 (3.27−14.24) in the age group of >60 years), suburban living (OR (95% CI) 2.2 (1.43−3.34)) and contact with soil (OR (95% CI) 1.4 (1.01−1.94)). This first large-scale study on toxoplasmosis in the general population in Serbia shows the lowest prevalence ever reported in this country. Moreover, the novel perspective on risk factors provides an updated basis for future prevention programs.

Postnatal ocular toxoplasmosis in immunocompetent patients.

INTRODUCTION: Ocular toxoplasmosis is the most common cause of infectious posterior uveitis worldwide. It can be prenatal or postnatal in origin. Despite estimations that postnatal ocular toxoplasmosis is more prevalent, only several cases of proven postnatal ocular toxoplasmosis have been reported in non-epidemic settings. Here, the clinical evolution of ocular toxoplasmosis of conclusively proven postnatal origin in immunocompetent patients is reported. METHODOLOGY: Postnatal ocular toxoplasmosis was diagnosed based on clinical diagnosis supported by the longitudinal detection of Toxoplasma gondii-specific IgG, IgM and IgA antibodies in the serum as well as by direct detection of the parasite (bioassay) and/or its DNA (real-time PCR) in aqueous humor. RESULTS: Three cases involved adults in whom ocular toxoplasmosis developed during primary T. gondii infection, as part of the clinical presentation in two and as the sole manifestation in one patient. The fourth patient was a case of inactive ocular toxoplasmosis in a 14-year-old boy, where postnatal infection was confirmed by exclusion of maternal infection. The causative parasite strain was genotyped in only one case and it belonged to genotype II, the dominant type in Europe. One patient acquired the infection in Africa, suggesting an atypical strain. CONCLUSIONS: The distinction between prenatal and postnatal ocular toxoplasmosis is only possible in particular clinical situations, and requires extensive laboratory investigation. Genotyping of the parasite strain involved may be important, particularly if atypical strains are suspected, requiring tailored treatment approaches.

Toxoplasma gondii Genotypes Circulating in Serbia-Insight into the Population Structure and Diversity of the Species in Southeastern Europe, a Region of Intercontinental Strain Exchange.

In Europe, Toxoplasma gondii lineage II is dominant, and ToxoDB#1 the most frequently occurring genotype. The abundance of lineage III genotypes varies geographically and lineage I are rare, yet present in several regions of the continent. Data on the T. gondii population structure in southeastern Europe (SEE) are scarce, yet necessary to appreciate the diversity of the species in Europe. To help fill this gap, we genotyped 67 strains from nine species of intermediate hosts in Serbia by MnPCR-RFLP, determined the population structure, and identified the genotypes using ToxoDB. A neighbor-joining tree was also constructed from the isolates genotyped on nine loci. While 42% of the total genotype population consisted of ToxoDB#1 and ToxoDB#2, variant genotypes of both lineages comprised 46% of the population in wildlife and 28% in domestic animals and humans. One genotype of Africa 4 lineage was detected in a human sample. Interestingly, the findings include one lineage III variant and one II/III recombinant isolate with intercontinental distribution, which appear to be moderately related to South American genotypes. Based on these findings, SEE is a region of underappreciated T. gondii genetic diversity and possible strain exchange between Europe and Africa.

Prospective Cohort Study of the Kinetics of Specific Antibodies to SARS-CoV-2 Infection and to Four SARS-CoV-2 Vaccines Available in Serbia, and Vaccine Effectiveness: A 3-Month Interim Report.

Real-life data on the performance of vaccines against SARS-CoV-2 are still limited. We here present the rates of detection and levels of antibodies specific for the SARS-CoV-2 spike protein RBD (receptor binding domain) elicited by four vaccines available in Serbia, including BNT-162b2 (BioNTech/Pfizer), BBIBP-CorV (Sinopharm), Gam-COVID-Vac (Gamaleya Research Institute) and ChAdOx1-S (AstraZeneca), compared with those after documented COVID-19, at 6 weeks and 3 months post first vaccine dose or post-infection. Six weeks post first vaccine dose, specific IgG antibodies were detected in 100% of individuals fully vaccinated with BNT-162b2 (n = 100) and Gam-COVID-Vac (n = 12) and in 81.7% of BBIBP-CorV recipients (n = 148), while one dose of ChAdOx1-S (n = 24) induced specific antibodies in 75%. Antibody levels elicited by BNT-162b2 were higher, while those elicited by BBIBP-CorV were lower, than after SARS-CoV-2 infection. By 3 months post-vaccination, antibody levels decreased but remained ≥20-fold above the cut-off in BNT-162b2 but not in BBIBP-CorV recipients, when an additional 30% were seronegative. For all vaccines, antibody levels were higher in individuals with past COVID-19 than in naïve individuals. A total of twelve new infections occurred within the first 3 months post-vaccination, eight after the first dose of BNT-162b2 and ChAdOx1-S (one each) and BBIBP-CorV (six), and four after full vaccination with BBIBP-CorV, but none required hospitalization.

Aminoquinolines afford resistance to cerebral malaria in susceptible mice.

OBJECTIVES: Malaria treatment is impeded by increasing resistance to conventional antimalarial drugs. Here we explored the activity of ten novel benzothiophene, thiophene and benzene aminoquinolines. METHODS: In vitro testing was performed by the lactate dehydrogenase assay in chloroquine (CQ)-sensitive Plasmodium falciparum strain 3D7 and CQ-resistant (CQR) P. falciparum strain Dd2. In vivo activity was evaluated by a modified Thompson test using C57BL/6 mice infected with Plasmodium berghei ANKA strain. RESULTS: Nine of the ten compounds had a lower 50% inhibitory concentration (IC50) than CQ against the CQR strain Dd2. Five of these compounds that were available for in vivo evaluation were shown to be non-toxic. All five compounds administered at a dose of 160mg/kg/day for 3 days prolonged the survival of treated compared with untreated mice. Untreated control mice died by Day 7 with a mean parasitaemia of 15%. Among treated mice, a dichotomous outcome was observed, with a two-third majority of treated mice dying by Day 17 with a low mean parasitaemia of 5%, whilst one-third survived longer with a mean hyperparasitaemia of 70%; specifically, five of these mice survived a mean of 25 days, whilst two even survived past Day 31. CONCLUSIONS: The significant antimalarial potential of this aminoquinoline series is illustrated by its excellent in vitro activity against the CQRP. falciparum strain and significant in vivo activity. Interestingly, compounds ClAQ7, ClAQ9 and ClAQ11 were able to confer resistance to cerebral malaria and afford a switch to hyperparasitaemia to mice prone to the neurological syndrome.

Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts.

Toxoplasma gondii is an obligate intracellular parasite infecting up to one third of the human population. The central event in the pathogenesis of toxoplasmosis is the conversion of tachyzoites into encysted bradyzoites. A novel approach to analyze the structure of in vivo-derived tissue cysts may be the increasingly used computational image analysis. The objective of this study was to quantify the geometrical complexity of T. gondii cysts by morphological, particle, and fractal analysis, as well as to determine if it is impacted by parasite strain, cyst age, and host type. A total of 31 images of T. gondii brain cysts of four type-2 strains (Me49, and local isolates BGD1, BGD14, and BGD26) was analyzed using ImageJ software. The parameters of interest included diameter, circularity, packing density (PD), fractal dimension (FD), and lacunarity. Although cyst diameter varied widely, its negative correlation with PD was observed. Circularity was remarkably close to 1, indicating a perfectly round shape of the cysts. PD and FD did not vary among cysts of different strains, age, and derived from mice of different genetic background. Conversely, lacunarity, which is a measure of heterogeneity, was significantly lower for BGD1 strain vs. all other strains, and higher for Me49 vs. BGD14 and BGD26, but did not differ among Me49 cysts of different age, or those derived from genetically different mice. The results indicate a highly uniform structure and occupancy of the different T. gondii tissue cysts. This study furthers the use of image analysis in describing the structural complexity of T. gondii cyst morphology, and presents the first application of fractal analysis for this purpose. The presented results show that use of a freely available software is a cost-effective approach to advance automated image scoring for T. gondii cysts.

Treatment of toxoplasmosis: Current options and future perspectives.

Toxoplasmosis is a worldwide parasitic disease infecting about one third of humans, with possible severe outcomes in neonates and immunocompromised patients. Despite continuous and successful efforts to improve diagnosis, therapeutic schemes have barely evolved since many years. This article aims at reviewing the main clinical trials and current treatment practices, and at addressing future perspectives in the light of ongoing researches.

Taeniosis and cysticercosis in Serbia, 1990-2018: Significance of standard of living.

OBJECTIVES: As is the case for all of Southeast Europe, Serbia is an area traditionally endemic for Taenia saginata and Taenia solium infections. This study was performed to analyse the epidemiological data on taeniosis and cysticercosis in Serbia for the period 1990-2018. METHODS: Data on cases of T. saginata and T. solium infection were collected via a systematic search of published articles, the grey literature, and official reports, as well as by performing clinical observational studies of patients treated in the departments for infectious diseases of hospitals and university clinics in Serbia. RESULTS: A total of 212 cases of taeniosis were reported, all between 1997 and 2004 when taeniosis was notifiable (incidence range 0.04-0.9/100 000 population/year). From 1990 to 2018, 170 cases of cysticercosis (all but one of neurocysticercosis), were registered (incidence range 0-0.29/100 000 population/year), with a strong decrease since 2000 and a single case in the last 9 years. The annual number of cases of both taeniosis (Pearson's r = 0.914, p = 0.001) and cysticercosis (Pearson's r = 0.582, p = 0.014) correlated with the consumer price index. CONCLUSIONS: In Serbia, T. saginata and T. solium infections are autochthonous but occur only sporadically. However, the potential for re-emergence exists, depending on the socio-economic state of the country.

Examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy.

Malaria remains a major disease in the developing world and globally is the most important parasitic disease causing significant morbidity and mortality. Because of widespread resistance to conventional antimalarials, including chloroquine (CQ), new drugs are urgently needed. Here we report on the antimalarial efficacy, both in vitro and in vivo, of a series of aminoquinoline derivatives with adamantane or benzothiophene as a carrier. In vitro efficacy was evaluated by a lactate dehydrogenase (LDH) assay in cultures of a CQ-sensitive (3D7) and CQ-resistant (Dd2) strain of Plasmodium falciparum. Of a series of 26 screened compounds, 12 that exerted a growth inhibition rate of ≥50% were further examined in vitro to determine the 50% inhibitory concentration (IC50) values. Nine compounds shown in preliminary experiments to be non-toxic in vivo were evaluated in C57BL/6 mice infected with Plasmodium berghei ANKA strain using a modified Thompson test. All nine compounds examined in vivo prolonged the survival of treated versus untreated mice, four of which afforded ≥60% survival. Most notably, two of these compounds, both with the adamantane carrier, afforded complete cure (100% survival and parasite clearance). Interestingly, one of these compounds had no in vitro effect against the CQ-resistant P. falciparum strain. Better in vivo compared with in vitro results suggest a role for compound metabolites rather than the compounds themselves. The results presented here point to adamantane as a carrier that enhances the antimalarial potential of aminoquinolines.

Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy.

To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy.I n the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment.

Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 µM and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 µM). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 ± 0.37 µM). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.

[Toxoplasmosis and Pregnancy: Reliability of Internet Sources of Information].

INTRODUCTION: Health education of women of childbearing age has been shown to be an acceptable approach to the prevention of toxoplasmosis, the most frequent congenitally transmitted parasitic infection. OBJECTIVE: The aim of this study was to evaluate the Internet as a source of health education on toxoplasmosis in pregnancy. METHODS: A group of 100 pregnant women examined in the National Reference Laboratory for Toxoplasmosis was surveyed by a questionnaire on the source of their information on toxoplasmosis. We also analyzed information offered by websites in the Serbian and Croatian languages through the Google search engine, using "toxoplasmosis" as a keyword. The 23 top websites were evaluated for comprehensiveness and accuracy of information on the impact of toxoplasmosis on the course of pregnancy, diagnosis and prevention. RESULTS: Having knowledge on toxoplasmosis was confirmed by 64 (64.0%) examined women, 40.6% (26/64) of whom learned about toxoplasmosis through the Internet, 48.4% from physicians, and 10.9% from friends. Increase in the degree of education was found to be associated with the probability that pregnant women would be informed via the Internet (RR=3.15, 95% CI=1.27-7.82, p=0.013). Analysis of four interactive websites (allowing users to ask questions) showed that routes of infection were the most common concern, particularly the risk presented by pet cats and dogs, followed by the diagnosis of infection (who and when should be tested, and how should the results be interpreted). Of 20 sites containing educational articles, only seven were authorized and two listed sources. Evaluation confirmed that information relevant to pregnant women was significantly more accurate than comprehensive, but no site gave both comprehensive and completely accurate information. Only four sites (20%) were good sources of information for pregnant women. CONCLUSION: Internet has proved itself as an important source of information. However, despite numerous websites, only a few offer reliable information to the Serbian (or Croat) speaking community, and none present complete and accurate information relevant to pregnant women.