Toxoplasmosis in Serbia: time for an action plan

Known for a century, Toxoplasma gondii has been studied in Serbia half this time, ever since the introduction of the Sabin-Feldman test at the Institute for Medical Research (IMR) in 1959. However, despite 50 years of continuous efforts, exact data on the frequency of acute clinical disease, acute infections in pregnancy and congenital infection in the offspring are still lacking, due to the vague regulatory provision that toxoplasmosis is subject to reporting "in case of epidemiological indications". It is, however, clear that the major Toxoplasma-induced public health issue in Serbia, like elsewhere in Europe, is congenital toxoplasmosis (CT). Continuous monitoring of particular patient groups showed a dramatic decrease in the prevalence of infection over the past two decades, and a consequently increased proportion of women susceptible to infection in pregnancy, suggesting a potential increase in the incidence of CT. Studies of risk factors for infection transmission have provided data to guide national health education campaigns. It is expected that the recent appointment of the National Reference Laboratory for Toxoplasmosis as the focal point for the collection of data from the primary level, will provide the means for accurate assessment of the measure of the problem, which is a prerequisite of an evidence-based nation-wide prevention program. In the meantime, health education of all pregnant women, focused at risk factors of major local significance, is advocated as a sound and financially sustainable option to reduce congenital toxoplasmosis

Efficacy of atovaquone combined with clindamycin against murine infection with a cystogenic (Me49) strain of Toxoplasma gondii

The efficacy of atovaquone (ATO) combined with clindamycin (CLI) against Toxoplasma gondii was examined in murine models of infection with a mouse-non-virulent (Me49) strain. Swiss-Webster mice inoculated by mouth with 10 or 20 cysts were treated with ATO and CLI alone or combined at dosages of ATO 5-100 and CLI 25-400 mg/kg/day for 2-4 weeks. Drug treatment was initiated (i) day 4 post-infection (acute infection), (ii) 3 months post-infection (chronic infection) and (iii) following a 2-3 week course of treatment with dexamethasone (DXM) alone or combined with cortisone-acetate (CA) introduced 3 months post-infection (reactivated toxoplasmosis). In acute infection, whereas treatment with any drug or drug combination significantly enhanced survival and reduced the brain cyst burden, in mice treated with ATO alone or combined with CLI, the cyst counts were significantly lower than in mice treated with CLI alone. In chronic infection, the decrease in the cyst burden observed 2 weeks after treatment with either drug alone was significant only in mice treated with the combined drugs. Most importantly, in reactivated toxoplasmosis, whereas an effect for the combined drugs was shown in mice suppressed with both DXM alone and combined with CA, in mice pre-treated with DXM a 3 week course of ATO greater than or equal to25 and CLI 50 mg/kg/day significantly increased survival and markedly decreased the cyst burden. The latter effect was long-term, since the cyst burdens in treated mice continued to decrease up to 3 months later, whereas they increased in the untreated mice. The results warrant clinical evaluation of the combination of ATO and CLI in the treatment of toxoplasmosis in both immunocompetent and, more importantly, immunosuppressed patients

Risk factors for toxoplasma infection in pregnant women in FYR of Macedonia

The aim of the study was to identify risk factors for Toxoplasma gondii infection in pregnant women in FYR of Macedonia. Retrospective analysis of serological and epidemiological data in a series of 235 pregnant women from Macedonia, tested for Toxoplasma infection between January 2004 and December 2005, showed on overall prevalence of infection of 20.4 %. Exposure to transmission factors significantly increased the risk of infection (RR = 1.989, 95 % Cl = 1.041-3.800, p = 0.037). The single infection transmission factor that was a predictor of infection in the whole series was exposure to soil (RR = 1.946, 95 % Cl = 1.026-3.692, p = 0.041). Based on prevalence and the established risk factors for Toxoplasma infection in Macedonia, the health education programme as a sustainable measure for the prevention of congenital toxoplasmosis should focus on educating women of generative age to avoid contact with soil (forming, gardening), and/to adhere to strict hygienic practices afterwards

Comparative evaluation of three commercial Toxoplasma-specific IgG antibody avidity tests and significance in different clinical settings

Determination of the avidity of specific IgG antibodies has become a generally accepted diagnostic aid for dating Toxoplasma infection. In this study, the Labsystems, VIDAS and EUROIMMUN Toxoplasma IgG avidity assays were compared on a series of 133 Toxoplasma IgG- and IgM-positive sera from symptomatic patients (n=28), from pregnant (n=43) and nonpregnant (n=26) women, and on 18 IgG-positive and IgM-negative sera from chronically infected patients. The results showed excellent concordance between the Labsystems and VIDAS tests in both the IgM-positive (r=0.82, kappa=0.771) and IgM-negative (kappa=0.609) sera, whilst the agreement of the EUROIMMUN assay with both the Labsystems and VIDAS tests in the IgM-positive sera was moderate (kappa=0.575 and kappa=0.525, respectively) and in the IgM-negative sera was poor (kappa=0.000). Analysis of the kinetics of the maturation of avidity in 13 patients in whom follow-up sera were available showed that, despite a general trend of maturation, in two patients the avidity did not become high during 6 and 11 months of follow-up. In view of the clinical setting, in the symptomatic patients, despite one case of complete discrepancy and five cases of partial discrepancy, the Labsystems and VIDAS tests were in almost perfect agreement (kappa=0.812), whilst the agreement in pregnant and non-pregnant women was substantial (kappa=0.754 and kappa=0.708, respectively). In conclusion, the Labsystems and VIDAS tests are equally reliable for the measurement of Toxoplasma IgG avidity; the choice of test should depend on the laboratory setup. The EUROIMMUN test may be an acceptable alternative in resource-limited settings, but should be used prudently

Effect of clindamycin in a model of acute murine toxoplasmosis

Objective: To characterize the antitoxoplasma activity of clindamycin in a murine model of acute toxoplasmosis. Methods: Rates of survival and mean survival times of Swiss Webster mice infected intraperitoneally with 106-102 tachyzoites of the RH strain of Toxoplasma gondii treated with clindamycin or sulfamethoxazole (positive control) or untreated (negative control) were compared. Survivors were submitted to examination of untreated brain tissue preparations, intraperitoneal and peroral subinoculations of brain tissue homogenates into fresh mice, and to pathohistology, including immunohistochemistry, of brain and lungs. Results: The effect of clindamycin treatment (400 mg/kg/day) on infected Swiss Webster mice was inoculum size dependent, ranging from no survivals in animals infected with 106 parasites, to 100% survivals with an inoculum of 102. Treatment initiated 24 h before and at time of infection prolonged mean survival times comparably to sulfamethoxazole, and significantly when compared to untreated controls. In contrast, treatment initiated 48 h postinfection with an inoculum of 106 did not postpone death. In the clindamycin-treated survivors, there was no biological or histologic evidence for the persistence of toxoplasma. Conclusions: The results obtained show that at an appropriate parasite dose/drug dose ratio, clindamycin is strongly toxoplasmacidal in a murine model of acute toxoplasmosis

Human giardiasis in Serbia: asymptomatic vs symptomatic infection

Despite the public health importance of giardiasis in all of Europe, reliable data on the incidence and prevalence in Western Balkan Countries (Serbia, Bosnia and Herzegovina, Croatia, Montenegro and FYR Macedonia) are scarce, and the relative contribution of waterborne and food-borne, or person-to-person and/or animal-to-person, transmission of human giardiasis is not yet clear. To provide baseline data for the estimation of the public health risk caused by Giardia, we here review the information available on the epidemiological characteristics of asymptomatic and symptomatic human infection in Serbia. Although asymptomatic cases of Giardia represent a major proportion of the total cases of infection, high rates of Giardia infection were found in both asymptomatic and symptomatic populations. No waterborne outbreaks of giardiasis have been reported, and it thus seems that giardiasis mostly occurs sporadically in our milieu. Under such circumstances, control measures to reduce the high prevalence of giardiasis in Serbia have focused on person-to-person transmission, encouraging proper hygiene, but for more targeted intervention measures, studies to identify other risk factors for asymptomatic and symptomatic infections are needed

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

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

Životni ciklus i osnovni parametri reprodukcije vrste Phlebotomus neglectus tonnoir, 1921 (Diptera, Psychodidae) u laboratorijskim uslovima

Laboratory investigations of the biology of the sand fly, Phlebotomus neglectus, including bionomic factors collected on the life history, behavior and feeding preferences of this species and the characteristics of its developmental biology are presented. In addition, we quantified the parameters of the population dynamics and life history of this species under laboratory conditions which are crucial for a better understanding of its role as a vector of Leishmania parasites in the eastern Mediterranean area.U radu su prikazani rezultati istraživanja osnovnih karakteristika životnog ciklusa i ponašanja vrste flebotomina Phlebotomus neglectus u laboratorijskim uslovima. Takođe, numerički su prikazani osnovni parametri dinamike populacije i pomoću tablica života određeni su ključni faktori životnog ciklusa u cilju boljeg razumevanja ove vrste flebotomina kao najvažnijeg prenosioca parazita Leishmania infantum u istočnom Mediteranu