[show abstract][hide abstract] ABSTRACT: Abstract Echinococcosis (hydatidosis) is traditionally endemic in Southeast Europe, Serbia included. In Serbia, echinococcosis is mandatory reportable, and this review analyzes the officially reported data as well as the research data published between 1998 and 2010. Official data on human and animal infections were obtained from the Institute of Public Health of Serbia (IPHS, 2010), and from the Ministry of Agriculture, Trade, Forestry and Water Management (MATFWM) and the Statistical Office, respectively. Published data were obtained by searching the Medline, Scopus, and Google databases using "echinococcosis," "hydatidosis," and "Serbia" as key words. In addition, the search included national journals and doctoral theses, as well as conference proceedings. Only Echinococcus granulosus has been reported in Serbia, with a total of 409 cases of human infection officially reported during the observed period as opposed to 820 cases described in clinical studies. No trend in the incidence of infection was shown among adults, but the number of cases in children continuously decreased over the period. Patients were more frequently female and from rural areas. Differences in the geographic distribution of cases were noted, with a lower incidence in the central part of country. Liver disease was by far the most common presentation, but cases of unusual cyst locations have been described. Among domestic animals, sheep were the most highly infected species. A decreasing incidence of echinococcosis in animals has been noted as of the 1970s. Echinococcosis continues to be endemic in Serbia in the 21st century, but despite predictions, neither official data nor those from clinical studies indicate its re-emergence. However, there is gross underreporting. Public health authorities should actively work to increase reporting, as only valid reported data provide an accurate basis for future control plans.
Foodborne Pathogens and Disease 10/2012; · 2.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: A sensitive real-time PCR technique was used to examine the distribution of Toxoplasma gondii in the blood and tissues of mice during acute and chronic infection. Groups of Swiss Albino mice, inoculated i.p. with 10(2) or 10(6) tachyzoites of the RH strain as a typical type-1 strain, or fed 10 cysts of the Me49 strain as a typical type-2 strain, were killed at different time points post-infection (p.i.), and blood and organs including the lungs, brain and liver were harvested for DNA extraction. Toxoplasma DNA was quantified by a real-time PCR targeted at the 529bp gene fragment, with a detection limit of a single parasite per g/ml of tissue. The results showed a strain- and dose-dependent spread of Toxoplasma. In infection with type-1 parasites, in case of a high infective dose, Toxoplasma DNA was detected within 24h p.i. in all analyzed tissues including the brain. Conversely, in case of a low infective dose, parasitaemia was undetectable early p.i., at a time when Toxoplasma DNA was detected in the tissues, but reached very high levels as infection progressed. With both infective doses, pre-death parasite burdens were higher in the blood than in the tissues, whereas the same loads in the lungs suggest that reaching these Toxoplasma burdens may be critical for survival. In infection with Me49 parasites, steady high parasite burdens were noted up to the end of the experiment at d42 only in the brain, parasitaemia was low but detectable throughout, and Toxoplasma DNA was completely cleared only from the liver. These data are important to better understand the pathogenesis of toxoplasmosis, and also as baseline data for the experimental evaluation of novel chemotherapeutics.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: Toxoplasma gondii infection acquired during pregnancy may lead to transplacental transmission and jeopardize the course and outcome of pregnancy,
leading to life-threatening disease in the fetus and the newborn. CASE REPORT: Here we present a case of medically terminated
pregnancy due to clinically manifested congenital toxoplasmosis (CT) which was proven serologically, as well as by bioassay.
Ultrasonographically visualized severe fetal ventriculomegaly in a seven-month pregnant 33-year-old woman with a history of
three months of lymphadenopathy was an indication for extensive testing for toxoplasmosis. Based on the serological results
obtained (high specific IgG antibodies of borderline but close-to-low avidity, along with the finding of specific IgM antibodies),
maternal infection was dated to the second trimester. Cord blood serology revealed IgG levels lower than those of the mother's,
but both specific IgM and IgA antibodies were detected, indicating fetal infection. Although Toxoplasma DNA was not detected in the cord blood sample by real-time PCR, fetal infection was definitely confirmed after six weeks
by cord blood bioassay results. While no morphologically recognizable Toxoplasma cysts were found, murine serology was positive. Since fetal morphological abnormalities, which could not be reversed by subsequent
treatment, were already advanced at the time of serological testing, the patient opted for termination of pregnancy. CONCLUSION:
This case demonstrates the potentially severe outcome of CT as a result of central nervous system affection, emphasizing the
need for prompt and precise prenatal diagnosis in case of maternal seroconversion, so that proper treatment may be introduced
in a timely manner.
HINTERGRUND: Toxoplasmagondii-Infektionen die während der Schwangerschaft auftreten, können über die Plazenta übertragen werden
und den Verlauf und das Ergebnis der Schwangerschaft gefährden und somit zu einer lebensbedrohlichen Erkrankung für den Fetus
oder das Neugeborene führen. FALLBERICHT: Wir berichten über den Fall eines Schwangerschaftsabbruches wegen einer klinisch
manifesten kongenitalen Toxoplasmose (CT), die sowohl serologisch wie auch in einem Bioessay bestätigt worden ist. Bei einer
33jährigen Frau im 7. Schwangerschaftsmonat mit einer Vorgeschichte von einer 3-monatigen Lymphadenopathie, die Anlass für
die Untersuchung auf Toxoplasmose war, fand sich sonographisch eine schwere Vergrößerung der fetalen Ventrikel. Basierend
auf den serologischen Ergebnissen (hochspezifischer IgG-Antikörper gemeinsam mit spezifischen IgM-Antikörpern) wurde die Diagnose
einer mütterlichen Infektion im 2. Trimester gestellt. Im Nabelschnurblut fanden sich serologisch niedrige IgG-Titer als im
mütterlichen Blut, jedoch waren sowohl spezifische IgM wie auch IgA-Antikörper vorhanden, die auf eine fetale Infektion hinwiesen.
Obwohl die Toxoplasma-DNA mittels PCR aus dem Nabelschnurblut nicht nachgewiesen werden konnte, bestätigte sich die fetale
Infektion nach 6 Wochen durch den Bioessay. Während morphologisch keine Toxoplasma-Zysten festgestellt werden konnten, war
der serologische Test positiv. Nachdem die fetalen morphologischen Veränderungen unter der angeschlossenen Therapie nicht
zurückentwickelt hatten und zum Zeitpunkt der serologischen Tests fortgeschritten waren, entschloss sich die Patientin zum
Schwangerschaftsabbruch. SCHLUSSFOLGERUNG: Dieser Fallbericht unterstreicht die potentielle schwere Schädigung durch eine
CT als Ergebnis eines ZNS-Befalls. Es ist daher die Notwendigkeit einer prompten und präzisen pränatalen Diagnostik im Falle
einer mütterlichen Serokonversion zu fordern, so dass eine adäquate Therapie rechtzeitig etabliert werden kann.
Wiener klinische Wochenschrift 04/2012; 123:43-46. · 0.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: Toxoplasma gondii infection acquired during pregnancy may lead to transplacental transmission and jeopardize the course and outcome of pregnancy, leading to life-threatening disease in the fetus and the newborn.
Here we present a case of medically terminated pregnancy due to clinically manifested congenital toxoplasmosis (CT) which was proven serologically, as well as by bioassay. Ultrasonographically visualized severe fetal ventriculomegaly in a seven-month pregnant 33-year-old woman with a history of three months of lymphadenopathy was an indication for extensive testing for toxoplasmosis. Based on the serological results obtained (high specific IgG antibodies of borderline but close-to-low avidity, along with the finding of specific IgM antibodies), maternal infection was dated to the second trimester. Cord blood serology revealed IgG levels lower than those of the mother's, but both specific IgM and IgA antibodies were detected, indicating fetal infection. Although Toxoplasma DNA was not detected in the cord blood sample by real-time PCR, fetal infection was definitely confirmed after six weeks by cord blood bioassay results. While no morphologically recognizable Toxoplasma cysts were found, murine serology was positive. Since fetal morphological abnormalities, which could not be reversed by subsequent treatment, were already advanced at the time of serological testing, the patient opted for termination of pregnancy.
This case demonstrates the potentially severe outcome of CT as a result of central nervous system affection, emphasizing the need for prompt and precise prenatal diagnosis in case of maternal seroconversion, so that proper treatment may be introduced in a timely manner.
[show abstract][hide abstract] ABSTRACT: The kinetics of Toxoplasma infection in the Balkans were reviewed.
Published reports on Toxoplasma infection in women of childbearing age in the last 30 years for all Balkan countries.
The dominant feature of Toxoplasma infection in the Balkans is a continuous decrease in the prevalence over time. Systematic monitoring of Toxoplasma infection prevalence in populations of women of childbearing age in Slovenia, Serbia and Greece over the last 30 years has shown a continuous significant decrease in all three countries. Moreover, a decrease has also been shown in Montenegro and Former Yugoslav Republic of Macedonia where Toxoplasma infection has been surveyed only during the past decade. Another region-wide feature is that the prevalence of infection currently does not surpass 50%. Furthermore, a decrease in Toxoplasma prevalence from the north to the south has been shown in the eastern part of the Balkan Peninsula, from southern Hungary (as a region neighbouring the Balkans at the north), over Serbia and FYRoM to northern Greece. Seasonality of infection, with significantly more cases of acute infection in the winter than in the summer, was observed in Slovenia in the west and Serbia in the east. Despite a common decreasing trend, different infection transmission risk factors seem predominant across the region; while contact with cats was discussed as important in Slovenia, consumption of undercooked meat was shown to be the leading risk factor in Serbia and Albania, and contact with soil in FYRoM and in northern Greece.
A decreasing trend of Toxoplasma prevalence over time in the Balkans is part of a changing pattern of Toxoplasma infection throughout Europe. Strategies for the prevention of congenital toxoplasmosis should take the infection dynamics into account.
[show abstract][hide abstract] ABSTRACT: Since 2000, travel of Serbian citizens to tropical areas has been slowly but steadily increasing. To determine the epidemiological and clinical characteristics of imported malaria in Serbia, we analyzed clinical history data of all travelers who presented at the Clinic for Infectious and Tropical Diseases in Belgrade after their return from tropical and subtropical areas between 2001 and 2009. The study series involved a total of 2981 travelers, and included both those with (847) and without (2134) health problems. Malaria was diagnosed in 102 cases (3.4% of all travelers; 12.0% of travelers with febrile episodes). Occurring at a rate of 6 to 16 cases per year, it was predominantly imported from Africa (92.2%), particularly from Equatorial Guinea (38.2%) and Nigeria (15.7%). The most frequent reason for travel was work/business. Patients were predominantly (87.3%) male, and the majority (66.7%) was between 40 and 59 years of age. A total of 15 (14.7%) patients took some form of anti-malarial chemoprophylaxis. The dominant causative species was Plasmodium falciparum (78), alone (70) or in mixed infection with P. vivax (5) and P. malariae (3). P. vivax, P. ovale and P. malariae as single agents were each identified in 11, 1 and 1 cases, respectively. Of the 11 cases in which the parasite was not detected, six appeared to be true submicroscopic cases. The clinical course of the disease was severe in 13 patients, all with falciparum malaria, of which three (2.9%) died. Rather than for all travelers, in Serbia screening for malaria should be mandatory in all travelers to endemic regions who present with fever irrespective of chemoprophylaxis history. Inadequate sensitivity of conventional diagnostic methods, illustrated by the cases of submicroscopic malaria, requires introduction of molecular diagnosis in routine practice.
[show abstract][hide abstract] ABSTRACT: ABSTRACT: A seroepizootiological study of Toxoplasma gondii infection involving a total of 488 slaughter pigs (468 market-weight pigs and 20 sows) in the Belgrade area, also included examination of the presence of T. gondii in the blood. Blood sampled at the slaughter line was examined for specific antibodies by modified direct agglutination, and blood clots of those seropositive at titres of 1:50-1:12800 were bioassayed in mice. The overall seroprevalence was 9.2%, significantly higher (p = 0.0063) in sows (30.0%) than in market-weight pigs (8.3%). Amongst the 22 bioassays performed, a total of 16 (72.7%) were positive, by observation of T. gondii cysts (12), seropositivity (7, including 3 in which cysts were not detected), and/or detection of T. gondii DNA by real-time PCR (12, including one otherwise negative). The positive bioassays originated from the blood of 12 market-weight pigs and 4 sows. Despite a general increase in the rate of demonstration of T. gondii with the increase in the specific antibody level, the association was not significant (p = 0.101). The risk of infection was 41-fold increased in sows vs market-weight pigs, and 15-fold in pigs from smallholders' finishing type farms vs those from large farrow-to-finish farms. The presence of viable T. gondii in a proportion of the samples indicates that some of the pigs had an active parasitaemia at the time of slaughter, which, along with the seroprevalence established, points to a potential source of human infection in Serbia. This is the first report on parasitaemia in naturally infected swine.
Veterinary Research 01/2011; 42(1):17. · 3.43 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the role of synanthropic rodents in the epidemiology of urban toxoplasmosis, Toxoplasma gondii infection was examined in 144 rats (Rattus norvegicus) and 12 mice (Mus musculus) captured using live animal traps in three locations in Belgrade city characterized by poor housing and degraded environment. In rats, specific IgG antibodies were detected by modified agglutination test in 22 (27.5%) of the 80 blood samples available. Toxoplasma brain cysts were microscopically detected in 11 (7.6%), and Toxoplasma DNA by real-time polymerase chain reaction was demonstrated in 15 (10.4%) animals. Of these, both cysts and Toxoplasma DNA were detected in five (3.5%) rats. In mice, cysts were observed in 3 (25%), but Toxoplasma DNA was detected in even 10 (83.3%) animals, including all 3 with morphologically recognized cysts. Being a link in the chain of Toxoplasma infection, the existence of urban rodent reservoirs of infection represents a public health risk.
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: Seasonal variations in the occurrence of toxoplasmosis have been studied only sporadically. We thus examined the seasonal distribution of acute toxoplasmosis in Serbia during a 4-year period (2004-2008).
A total of 391 consecutive symptomatic (recent lymphadenopathy) and 715 asymptomatic (women tested for obstetric reasons) patients were tested for Toxoplasma immunoglobulin G (IgG) (including IgG avidity) and IgM antibodies. The distribution of patients with acute infection, and of all patients from both groups, was analyzed for seasonality. In addition, factors (including undercooked meat consumption, contact with cats and with soil) possibly contributing to seasonality were analyzed in patients with acute infection (cases) matched by age, sex, and time (month and year) of infection (symptomatic) or presentation (asymptomatic) with seronegative patients (controls).
Acute toxoplasmosis was serologically (IgG avidity low, IgM positive) diagnosed in 39 (10.0%) symptomatic and 38 (5.3%) asymptomatic patients. In both groups, monthly distribution of acute infections showed significant (p < 0.0001) seasonality, which was related to the four seasons of the year (p < 0.0001). Importantly, the observed seasonality was not related to the distribution of all examined patients in either group (p < 0.001). In the symptomatic patients, acute infections occurred more often between October and March (p = 0.0486). Although more asymptomatic acute infections were diagnosed between February and July (p = 0.0037), low IgG avidity suggests that infection had occurred within the previous trimester (between November and April). Undercooked meat consumption was shown as a risk factor for symptomatic infection in the October-March period (odds ratio 7.67, 95% confidence interval 1.61-36.45).
Seasonality patterns should be taken into account in the health education guidelines for the prevention of toxoplasmosis in pregnant women.
[show abstract][hide abstract] ABSTRACT: Peroxynitrite was hypothesized to be involved in the pathogenesis of multiple sclerosis (MS) through its various neurotoxic effects. Uric acid (UA) was shown to be a strong peroxynitrite scavenger.
We analyzed cerebrospinal fluid (CSF) and serum UA concentrations in 30 MS patients and 20 controls with non-inflammatory neurological diseases (NIND) and correlated these findings with demographic and clinical characteristics of MS patients. Disease activity was assessed by brain magnetic resonance imaging (MRI) and the CSF/serum albumin quotient as an indicator of the state of blood-brain-barrier (BBB).
Serum UA concentrations were found to be significantly lower in MS patients compared with controls (p=0.019). CSF UA concentrations were lower in MS patients as compared to controls, as well as in patients with active MS (clinical and/or MRI activity) in comparison to patients with inactive MS or controls, but these differences were not statistically significant. Significant correlation was found between CSF and serum UA concentrations (p=0.016) in MS patients, but not in controls; and between CSF UA concentrations and the CSF/serum albumin quotient in MS patients (p=0.043), but not in controls.
Our results support the significance of UA in the pathogenesis of MS. Decreased serum UA concentrations in MS patients might be due to both intrinsically reduced antioxidant capacity and increased UA consumption in MS. CSF UA concentrations may not be a reliable marker of disease activity in MS since its concentration is dependent on leakage of UA molecules from serum through the damaged BBB and the balance between consumption/production within the central nervous system (CNS).
Clinical Chemistry and Laboratory Medicine 07/2009; 47(7):848-53. · 3.01 Impact Factor
[show abstract][hide abstract] ABSTRACT: Host lipids have been implicated in the pathogenesis of Toxoplasma gondii infection. To determine if Toxoplasma infection influences the lipid status in the normal host, we assessed serum lipids of Swiss-Webster mice during infection with the BGD-1 strain (type-2) at a series of time points. Mice were bled at days zero and 42 post-infection, and subgroups were additionally bled on alternating weeks (model 1), or sacrificed at days zero, 14 and 42 (model 2) for the measurement of total cholesterol (Chl), high density lipoproteins (HDL), low density lipoproteins (LDL) and triglycerides and adiponectin. At day 42, brains were harvested for cyst enumeration. A significant decrease (p = 0.02) in HDL and total Chl was first noted in infected vs. control mice at day 14 and persisted to day 42 (p = 0.013). Conversely, LDL was unaltered until day 42, when it increased (p = 0.043). Serum LDL levels at day 42 correlated only with cyst counts of above 300 (found in 44% mice), while the change in HDL between days zero and 42 correlated with both the overall mean cyst count (p = 0.041) and cyst counts above 300 (p = 0.044). Calculated per cyst, this decrease in HDL in individual animals ranged from 0.1-17 micromol/L, with a mean of 2.43 +/- 4.14 micromol/L. Serum adiponectin levels remained similar between infected and control mice throughout the experiment.
Memórias do Instituto Oswaldo Cruz 04/2009; 104(2):175-8. · 1.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: To identify areas of risk for canine-related zoonoses in Serbia, the aim of this study was to provide baseline knowledge about intestinal parasites in 151 dogs (65 household pets, 75 stray and 11 military working dogs) from Belgrade. The following parasites, with their respective prevalences, were detected: Giardia duodenalis (14.6%), Ancylostomatidae (24.5%), Toxocara canis (30.5%), Trichuris vulpis (47.0%) and Taenia-type helminths (6.6%). Of all examined dogs, 75.5% (114/151) were found to harbour at least one parasite species. Of these, mixed infections with up to four species per dog occurred in 44.7% (51/114). Infections with all detected species were significantly higher (p < 0.05) in military working (100%) and stray dogs (93.3%) versus household pets (50.8%). Among all parasites, agents with zoonotic potential including Giardia, Ancylostomatidae and Toxocara were detected in 58.3% (88/151) of all examined dogs with a significant difference (p < 0.05) among the subgroups (100%, 62.7% and 46.2% for military working dogs, stray dogs and household pets, respectively). The high prevalence of zoonotic parasites registered in the dog population from a highly urban area in south-eastern Europe indicates a potential risk to human health. Thus, veterinarians should play an important role in helping to prevent or minimise zoonotic transmission.
[show abstract][hide abstract] ABSTRACT: Despite its capacity for sexual reproduction and global distribution, Toxoplasma gondii has a highly clonal structure, with the majority of isolates belonging to three distinct clonal types. Congenital toxoplasmosis has been associated with type I and type II strains. We here present the first characterization of a T. gondii strain (BGD1) from South-East Europe, isolated from the umbilical blood of a 24-week-old fetus in Serbia. Genotyping, performed by PCR-RFLP using a set of nested PCR markers (5'SAG2, 3'SAG2, BTUB, SAG3, and GRA6), showed that the BGD1 strain possessed a type II genotype. The cytokine patterns in Swiss-Webster mice inoculated with brain cysts of BGD1 and the prototype type II ME49 strain were similar until 180 days post-infection, with highly elevated IFN-gamma, IL-12 and IL-10 by d7 and decreasing thereafter. While both strains induced pneumonia and hepatitis in acute infection (d14), chronic infection (d56) was characterized, in addition to hepatitis, by severe meningoencephalitis, associated with numerous brain cysts. Thus, the BGD1 strain of T. gondii has type II genotypic and immunologic characteristics, but unlike other type II strains of human origin, induces severe encephalitis, making it an alternative to the sheep-derived ME49 strain for experimental models of infection.
Microbes and Infection 08/2006; 8(8):2206-12. · 2.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Toxoplasmosis is a globally distributed zoonosis with a clinical impact in the unborn fetus and in the immunosuppressed individual. In Serbia, studies of risk factors for Toxoplasma gondii infection in humans have shown that the relatively high prevalence is associated mainly with consumption of undercooked meat and/or meat products. However, data on T. gondii infection in domestic animals mostly used for human consumption are scarce. We thus conducted a cross-sectional survey on the seroprevalence of T. gondii infection in a representative sample of cattle, sheep and pigs from different regions of Serbia between June 2002 and June 2003, and analyzed the main risk factors associated with the infection. Sera from 611 cattle (yearlings and adults of both sexes), 511 ewes, and 605 pigs (market-weight and sows), were examined for T. gondii antibodies by the modified agglutination test. The seroprevalences determined were 76.3% in cattle, 84.5% in sheep and 28.9% in pigs. The antibody levels ranged from 1:25 to 1:400 in cattle, and up to 1:25,600 in sheep and to 1:12,800 in pigs. Among the seropositive, the proportion of high antibody levels (> or =1:1600), suggestive of acute infection, was 10% in sheep, and 4% in pigs. Possible association of the infection with biologically plausible risk factors including gender, age, herd size/farm type, type of housing, feeding practices and region, was analyzed by univariate analysis, and variables significant at P< or =0.1 were included in multivariate logistic regression models. The results showed that risk factors for cattle were small herd size (odds ratio, OR=2.19, 95% confidence interval, CI=1.28-3.75, P=0.004) and farm location in Western Serbia (OR=2.04, 95% CI=1.10-3.79, P=0.024), while housing in stables with access to outside pens was protective (OR=0.37, 95% CI=0.21-0.67, P=0.001). In sheep, an increased risk of infection was found in ewes from state-owned flocks (OR=4.18, 95% CI=2.18-8.00, P<0.001) vs. private flocks, and, interestingly, also in those from Western Serbia (OR=4.66, 95% CI=1.18-18.32, P=0.028). In pigs, the risk of infection was highly increased in adult animals (OR=3.87, 95% CI=2.6-5.76, P<0.001), as well as in those from finishing type farms (OR=3.96, 95% CI=1.97-7.94, P<0.001). In addition to providing data on the current T. gondii seroprevalence in meat animals in Serbia, the results of this study show the main risk factors associated with infection, thereby pointing to the type of preventive measures to reduce T. gondii infection.
[show abstract][hide abstract] ABSTRACT: The antitoxoplasmic activity of spiramycin (SPI) was evaluated in murine models of infection using a type-1 (RH) or type-2 (Me49) strain of Toxoplasma gondii. In mice infected with 10(2) tachyzoites of the RH strain, treatment with 100 and 200 mg SPI/kg/day had only a limited effect; despite some dose-dependent prolongation of survival, it was unable to protect mice against death. In contrast, in acute infection induced by peroral inoculation of 10, but not 20, cysts of the Me49 strain, a 3-week course of 100 mg SPI/kg/day and a 4-week course of 200 mg/kg/day significantly enhanced protection and markedly reduced brain cyst burdens at 6 months post infection (p.i.). In chronic infection established by inoculation of 10 cysts 3 months previously, a 3-week course of 200 mg SPI/kg/day resulted in significantly decreased brain cyst burdens compared with controls, both 2 weeks after treatment cessation and by 6 months p.i. Although a favourable effect on chronic infection may be specific for mice, these data merit investigation, since they may have clinical ramifications.
International Journal of Antimicrobial Agents 04/2005; 25(3):226-30. · 4.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mouse-virulent RH strain of Toxoplasma gondii is generally considered to have lost its cyst-forming capacity, and conversion of RH tachyzoites into cysts in non-immune mice has previously been shown exclusively following early treatment with sulfadiazine (SDZ). We here describe the development of tissue cysts in mice infected with RH strain parasites and treated with atovaquone (ATO) combined with pyrrolidine dithiocarbamate (PDTC). Groups of Swiss-Webster mice infected intraperitoneally (i.p.) with 10(2) RH tachyzoites were treated with 5, 25 and 100 mg of ATO/kg per day alone or combined with PDTC at 250 mg/kg per day from day 1 postinfection (p.i.) for 14 days. A total of 19 mice survived the 6-week observation period. Of these, brain cysts were recovered in nine (47%), with burdens ranging from 50 to 3120 (mean +/- S.D. = 622 +/- 963). All cyst-harboring mice had high specific IgG antibody levels (1:10,240-1:40,960, corresponding to 500-2000 IU/ml), as did one mouse in which cysts were not demonstrated, which was therefore included in the group of mice with residual infection. Bioassay performed to test the infectivity of these cysts produced acute lethal toxoplasmosis following i.p. inoculation in all instances (100%), and importantly, following peroral inoculation in four (29%). The recovered tachyzoites were highly infectious. In addition, significantly elevated interferon gamma (IFN-gamma) in the treated mice which developed residual infection compared with any group of infection-free (treated or subinoculated) mice, indicates immunological control of the parasite in the latent form. In conclusion, early treatment of mice infected with T. gondii RH tachyzoites with ATO and PDTC induces conversion into tissue cysts, thus providing a new model for studying the mechanism(s) of T. gondii stage conversion.
Microbes and Infection 02/2005; 7(1):49-54. · 2.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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 > or = 25 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.
Journal of Antimicrobial Chemotherapy 12/2002; 50(6):981-7. · 5.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Clinical Microbiology and Infection 03/1997; 3(1):89-94. · 4.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Toxoplasmosis has long been known as a major cause of perinatal morbidity. Acute infection in pregnancy may lead to fetal infection and subsequent fetal loss or birth of a manifestly or latently infected infant. However, it is a preventable disease. In Europe, significant variations have been shown to occur not only between countries but also within a given country indicating local variations in the influence of epidemiological factors contributing to infection. Thus, many European countries have implemented prevention programs in measure with the respective estimated risk of congenital toxoplasmosis. Since in view of its cost, a general screening-in-pregnancy program is at present not an option in Serbia & Montenegro, insight into the risk factors of particular local significance may therefore improve the quality of and the compliance with the hygienic and dietetic advice given to pregnant women as a preventive measure, as well as identify the particular subpopulations at an increased risk of infection, who may then be selectively screened.
A retrospective study of risk factors for Toxoplasma gondii infection based on serological and epidemiological data (questionnaire) was performed in a series of 2936 women aged 15-49 years from throughout Serbia tested in our laboratory between 1988 and 1997. Inclusion criteria included availability of serological and epidemiological data (as specified below). Specific anti-Toxoplasma antibodies were detected by the reference Sabin-Feldman dye test as modified by Desmonts into the lysis test. The questionnaire included questions on age (stratified into five-year groups), degree of education (modalities: grade school, secondary or university level), and community of residence (urban/suburban), as well as on life-style habits pertaining to infection transmission risk factors: consumption of undercooked meat, exposure to soil, and exposure to cats (pet cat ownership). In addition, the year of entry into the study was taken as a variable per se.
The difference in the rates of infection between groups was evaluated by the chi-square test (chi 2). Logistic regression (univariant and multivariant approaches) was used to analyze the association between Toxoplasma infection and the specific demographic and epidemiological factors.
The overall prevalence of infection was 69%, but with very wide variations both over time (decreasing from 86% in 1988 to 39% in 1997) and region (40-90%). The risk of infection increased from the south to the north (RR = 0.97, CI = 0.94-0.98). Within Belgrade, the risk was higher in urban than in suburban zones (RR = 0.79, CI = 0.64-0.93). The single infection transmission factor that was shown to be a predictor of infection in the whole study group was undercooked meat consumption (RR = 1.6, CI = 1.2-2.1), while exposure to soil was a predictor only in women aged 15-19 (RR = 10.3, CI = 2.7-38.6). Owing pet cats had no influence. While T. gondii infection was not associated with pathological pregnancies (p = 0.51) in the whole study population, it was significantly associated with pathological pregnancies in women exposed to both undercooked meat consumption (p = 0.009) and in those aged 15-19 in contact with soil (p = 0.022), as well as in women residing in highly urban communities (p = 0.048).
The dramatic decrease in the prevalence of T. gondii infection over the nineties resulted in a rising proportion of women exposed to infection in pregnancy and consequently in an increased risk of congenital toxoplasmosis. Since the financial status of the country's health system does not allow for a general screening-in-pregnancy program, we propose, based on the above data, health education of all pregnant women in combination with serological testing of those exposed to predictors of infection as an epidemiologically sound and financially sustainable alternative.
Srpski arhiv za celokupno lekarstvo 131(3-4):162-7. · 0.23 Impact Factor