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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.

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.

T oxoplasma gondii is a protozoan parasite distributed worldwide and infecting one-third of the global population. Infection is acquired by ingestion of parasites via consumption of undercooked meat containing tissue cysts or of water, fruits, or vegetables contaminated with oocysts. In immunocompetent individuals, primary infection results in the formation of tissue cysts and in serological evidence of infection. However, in immunocompromized patients, such as hematopoietic stem cell transplant (HSCT) recipients, toxoplasmosis is often a life-threatening opportunistic infection arising either from transmission of the parasites via a graft from a seropositive donor to a seronegative recipient or, far more frequently, from reactivation of a preexisting latent infection in a seropositive recipient, regardless of the donor's serological status (1). After allogeneic HSCT, studies have shown an incidence of invasive toxoplasmosis among seropositive recipients of 4% to 6%, with an estimated mortality rate of 60% to 90% (2, 3).Nijmegen breakage syndrome (NBS) is a rare, autosome-recessive DNA repair disorder characterized by microcephaly with normal intelligence, facial dysmorphia (bird-like facial features), primary immunodeficiency, and a predisposition to lymphoid malignancies at a young age (4, 5). Treatment of NBS-related malignancies is challenging due to the chromosomal instability and immunodeficiency which make the patients more susceptible to the toxic effects of standard chemotherapy and radiation. Although lymphoid malignancies occurring in NBS patients can be successfully brought into remission using standard chemotherapy regimens with minor dose modifications (6, 7), a high rate of treatment failure and relapse has been observed (8). An alternative treatment option for malignancies in NBS is HSCT from HLAidentical donors, which has been shown not only to correct humoral and cellular immunodeficiency but also to lower the secondary malignancy rate (9).We here present a case of an early and fulminant post-HSCT reactivation of toxoplasmosis caused by an atypical T. gondii strain in a young patient with NBS that contributed to a subsequent fatal outcome within 40 days after transplantation. This case is the first report of increased clinical severity of toxoplasmosis caused by an atypical strain in the setting of immunosuppression. It also stresses the value and necessity of the use of quantitative molecular methods to monitor T. gondii reactivation in cases of reactivation risk.(The results of this study have been presented in part at the 11th European Multicolloquium of Parasitology [EMOP XI],

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.

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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.

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.In 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.