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

Epidemiology of Taenia solium infection in the Russian Federation in the last 20 years: a systematic review

Taenia solium is a zoonotic parasite that causes taeniasis and cysticercosis in humans (as final hosts) and cysticercosis in pigs (as intermediate hosts). The Russian Federation (RF) is traditionally considered as endemic for this zoonosis. However, the epidemiological data on T. solium infection have not been reviewed for the past 20 years, in which time dynamic economical and societal changes have occurred in the RF. The aim of this systematic review was to analyse the status of T. solium infection in RF in the 2000–2019 period. A literature search was conducted, which collected published articles, grey literature and official data on the epidemiology of T. solium taeniasis and cysticercosis in the RF published from 2000. From a total of 2021 articles and 24 official reports originally returned by the search, data were extracted from 12 full text articles and 11 official reports. Taenia solium taeniasis was continuously reported in the RF between 2000 and 2019, with a tenfold decrease in the incidence, from 0.2 per 100,000 population in 2000 to 0.023/100,000 in 2019. Also, the number of administrative units where taeniasis was detected continuously decreased. Cysticercosis in pigs had a declining trend after 2006. In conclusion, although decreasing, T. solium infection is still endemic in several regions and suspected to be endemic in most of the RF

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

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

Implementacija treće doze vakcine protiv SARS-CoV-2 u preporuke širom sveta otvorila je polje istraživanja heterologog pristupa revakcinaciji, odnosno kombinacije primarne serije vakcine i treće doze različite vakcinalne platforme. Iako je literatura bogata radovima na temu heterologog pristupa, imunogenost i trajanje humoralnog imunskog odgovora nakon kombinacije inaktivisane BBIBPCorV i iRNK vakcine nisu dovoljno istraženi. Stoga, cilj ove studije bio je ispitivanje razlike u imunogenosti i dugotrajnosti humoralnog imunskog odgovora u okviru perioda od šest meseci nakon treće doze kod homologog (tri doze BNT162b2) i heterologog (BBIBP-CorV/BNT162b2) pristupa revakcinaciji tokom Omikron talasa u Srbiji. U studiju je uključen 91 ispitanik, od kojih se 55 odlučilo za homologi a 36 za heterologi pristup. Serumi ispitanika analizirani su u četiri vremenske tačke: šest meseci nakon prve doze, a zatim tri nedelje, tri meseca i šest meseci nakon treće doze. IgG antitela specifična za receptor-vezujući domen “šiljastog” (eng. spike) proteina detektovana su BioMerieux VIDAS SARS-CoV-2 IgG testom. Tri nedelje nakon treće doze, oba pristupa revakcinaciji dovela su do značajnog porasta u koncentraciji antitela (p<0.0001). Štaviše, ispitanici koji su se opredelili za heterologu kombinaciju imali su statistički značajno više koncentracije antitela od homologe grupe, u kontrolnim vremenskim tačkama na tri nedelje i tri meseca nakon treće doze (p=0.025, p=0.0006). Međutim, značajan pad humoralnog imunskog odgovora zapažen je tokom vremena kod oba pristupa. Većina infekcija nakon vakcinacije registrovana je u periodu između tri i šest meseci nakon treće doze (n=22), a ukupna incidencija ovih infekcija za posmatrani period iznosila je 36.36% (20/55) nakon homologog i 16.67% (6/36) nakon heterologog pristupa. Međutim, ispitanici sa potvrđenom infekcijom nakon vakcinacije nisu imali pneumoniju niti su bili hospitalizovani. Iako je heterologi pristup indukovao više koncentracije antitela, naši rezultati ukazuju da su i heterologi i homologi pristup indukovali potentan humoralni imunski odgovor i odgovarajuću zaštitu od hospitalizacije i smrtnog ishoda tokom Omikron talasa. Međutim, opadanje imunskog odgovora opaženo kod oba vakcinalna pristupa u periodu od šest meseci, kao i konstantna opasnost od pojave novih pretećih varijanti, ukazuje na potrebu preispitivanja trenutne vakcinalne strategije.Worldwide implementation of the third dose of vaccine against SARS-CoV-2 opened a new field of research concerning the heterologous boost i.e., the combination of the primary vaccine series and a different vaccinal platform for the third dose. Although literature is replete with studies of heterologous boosts, longevity and immunogenicity of the inactivated BBIBP-CorV and mRNA BNT162b2 combination remains under-explored. Thus, the aim of this study was to evaluate the differences in immunogenicity and longevity of the humoral immune response within six months after the third dose in both homologous (BNT162b2) and heterologous (BBIBP-CorV/BNT162b2) vaccination setting, and to assess the real-life data in the middle of the Omicron surge in Serbia. A total of 91 individuals were included in this study, of which 55 received homologous and 36 heterologous boost. Serum samples were analyzed at four timepoints: six months after the first dose; three weeks, three months, and six months after the third dose. Specific IgG antibodies against the receptor-binding domain of the spike protein were detected using BioMerieux VIDAS SARS-CoV-2 IgG kit. Both groups showed a highly significant increase in antibody concentrations (p<0.0001) three weeks after the boost. Furthermore, comparison per timepoint has shown that recipients of heterologous boost had significantly higher antibody concentrations than homologous group, at three weeks and three months after the boost (p=0.025, p=0.0006). However, a significant decline in antibody response over time was noted for both strategies. The majority of breakthrough infections were registered in the period between three and six months after the boost (n=22).Furthermore, total incidence was estimated at 36.36% (20/55) for homologous group, and 16.67% (6/36) for heterologous group. Most importantly, none of the recipients of the third dose developed pneumonia during the breakthrough infection, and none were hospitalized. In conclusion, although heterologous approach resulted in higher antibody concentrations, our findings imply that both homologous and heterologous boost induce potent humoral immune response and adequate protection against hospitalization and death in the Omicron setting. However, waning immune response registered for both types of boosts within six months and constant threats of new emerging variants, calls for an update of vaccine strategy

Novi derivati 4-aminohinolina kao umereni inhibitori parazita

Synthesis of novel aminoquinoline derivatives has been accomplished and their activity against malaria strains has been examined. The compounds showed moderate in vitro antimalarial activity against two P. falciparum strains, 3D7 (CQ susceptible clone) and Dd2 (CQ resistant clone). Three aminoquinolines were further examined for antimalarial efficacy in a mouse model using a modified Thompson test. In this model, mice were infected with P. berghei-infected red blood cells, and drugs were administered orally. Antimalarial 3 was found toxic at a dose of 320 (mg/kg)/day in 3/6 mice, however, 2/6 mice of the same group survived through day 31, and one of them was cured

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 falcipanim. Of a series of 26 screened compounds, 12 that exerted a growth inhibition rate of gt = 5% 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 herghei 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 gt = 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

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

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

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

Toksoplazmoza i trudnoća - pouzdanost informacija s interneta

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 web- sites (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.Uvod Zdravstveno prosvećivanje žena generativne dobi definisano je ranijim istraživanjima kao prihvatljiv pristup prevenciji toksoplazmoze, najznačajnije parazitske perinatalne infekcije. Cilj rada Cilj istraživanja je bio da se oceni uloga veb-sajtova u zdravstvenom prosvećivanju trudnica o toksoplazmozi. Metode rada Grupa od 100 trudnica pregledanih u Nacionalnoj referentnoj laboratoriji za toksoplazmozu anketirana je o izvorima njihovih saznanja o toksoplazmozi. Istovremeno su pregledani veb-sajtovi na srpskom i hrvatskom jeziku, i to prva 23 koja se preko pretraživača Google pojavljuju na zadatu reč 'toksoplazmoza'. Analizirani su i ocenjeni sveobuhvatnost i tačnost informacija koje se odnose na uticaj toksoplazmoze na trudnoću, dijagnostiku i prevenciju ove infekcije. Rezultati Da imaju saznanja o toksoplazmozi potvrdile su 64 (64%) anketirane trudnice, od kojih je 26 (40,6%) saznanja steklo pretraživanjem interneta, 31 (48,5%) informacije je dobila od lekara, a sedam (10,9%) od prijatelja. Sa većim stepenom obrazovanja trudnice povećavala se i verovatnoća da će trudnica biti informisana preko interneta (RR=3,15; 95% CI=1,27-7,82; p=0,013). Analiza podataka sa četiri interaktivna veb-sajta pokazala je da većinu žena, pre svega, interesuju putevi širenja infekcije, dok su sledeća po učestalosti bila pitanja o dijagnostici. Od analiziranih članaka sa 20 informativnih veb-sajtova, samo sedam je bilo autorizovano, dok su u dva navedeni izvori informacija. Analiza je pokazala da je tačnost informacija bila značajno veća nego sveobuhvatnost, da nijedan analizirani sajt ne daje potpuno sveobuhvatne i tačne informacije, te da su samo četiri sajta (20%) dobar izvor informacija za trudnice o toksoplazmozi. Zaključak Internet je za trudnice značajan izvor informacija o toksoplazmozi. Iako su veb-sajtovi brojni, malo je onih koji su dobar izvor potrebnih podataka za čitaoce sa srpskog (ili hrvatskog) govornog područja, a nijedan ne daje u potpunosti sve potrebne i tačne informacije