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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.

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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.

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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.

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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.

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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.

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