Drug Resistance in Toxoplasma gondii

Toxoplasma gondii (T. gondii) is a global protozoan parasite infecting up to one-third of the world population. Pyrimethamine (PYR) and sulfadiazine (SDZ) are the most widely used drugs for treatment of toxoplasmosis; however, several failure cases have been recorded as well; suggesting the existence of drug resistant strains. This review aims to give a systematic and comprehensive understanding of drug resistance in T. gondii including mechanisms of resistance and sites of drug action in parasite. Analogous amino acid substitutions in the Toxoplasma enzyme were identified to confer PYR resistance. Moreover, resistance to clindamycin, spiramycin, and azithromycin is encoded in the rRNA genes of T. gondii. However, T. gondii SDZ resistance mechanism has not been proved yet. Recently there has been a slight increase in SDZ resistance. That is why the majority of studies were carried out using SDZ. Six strains resistant to SDZ were found in clinical cases between 2013 and 2017 which among Brazilian T. gondii isolates, TgCTBr11, Ck3, and Pg1 were identified in human toxoplasmosis, as well as in livestock intended for human consumption. In conclusion, recent experimental studies in clinical cases have clearly shown that drug resistance in Toxoplasma is ongoing. Thus, establishing a more effective therapeutic scheme in the treatment of toxoplasmosis is critically needed. The emergence of T. gondii strains resistant to current drugs, reviewed here, represents a concern not only for treatment failure but also for increased clinical severity in immunocompromised patients. To improve the therapeutic outcome in patients, a greater understanding of the exact mechanisms of drug resistance in T. gondii should be developed. Thus, monitoring the presence of resistant parasites, in food products, would seem a prudent public health program

Status of human cystic echinococcosis based on hospital records in Mazandaran Province: A first registry-based evidence

Background: Human cystic echinococcosis, as an emerging neglected parasitic disease, is caused by tapeworms of the genus Echinococcus spp. Because of the medical and economic importance, this study aims to review the epidemiology and clinical features of hydatidosis in patients admitted to medical and surgical wards in three referral teaching hospitals over 15 years in Mazandaran Province, northern Iran. Methods: Data were collected from hospital records that were accessible via the hospital information system (HIS) between 2005 and 2019 (15 years).The demographic information (age, sex, living area, and occupation), dog contact, number of the cysts, types of organs involved, and history of disease recurrence were assessed. Results: One hundred twenty-one patients with human cystic echinococcosis (CE) were involved in the study, from whom 58 patients (47.93%) were male and 63 (52.07%) were female. The majority of patients were rural residents (64.46%) and also housewife (28.10%). Based on the results, only about 16.53% of the patients had history of close contacts with dogs. The liver was the organ involved in the most cases of CE. There were statistically significant differences between residence, occupation, history of close contacts with dogs, type of organs involved, number of cysts and history of disease recurrence (P < 0.05). Conclusions: Our data provides valuable registry-based information about CE in an endemic region. The data highlights that most patients lived in rural areas and were housewives. Additionally, they had a low rate of disease recurrence but a high rate of close contact with dogs. Moreover, further monitoring on registry-based program and strengthening the HIS in the provincial hospitals in the studied area are required

Anti-Toxoplasma Effects of Methanol Extracts of Feijoa sellowiana, Quercus castaneifolia, and Allium paradoxum

Objectives: The currently available agents for use against toxoplasmosis have serious limitations. Thus, the aim of the present study was to investigate the anti-Toxoplasma gondii (T. gondii) activities of methanol extracts of Feijoa sellowiana (F. sellowiana) (leaves and fruits), Quercus castaneifolia (Q. castaneifolia) (fruits), and Allium paradoxum (A. paradoxum) (leaves) in vitro and in vivo. Methods: Vero cells were treated with different concentrations (from 0 to 400 μg/mL) of the above extracts or with pyrimethamine at a dose of 50 mg/mL (positive control). Then, the viabilities of the T. gondii-infected cells were measured by using colorimetric MTT (3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide) assays. In addition, the survival rates of mice acutely infected with 2 × 104 RH strain tachyzoites of T. gondii were examined in vivo after intraperitoneal injection of the extracts at doses of 100 and 200 mg/kg/day for 5 days. Results: In the in vitro anti- T. gondii assay, the IC50 values were 12.77, 180.2, 74.73, 213.2 and 163.8 μg/mL, and the selectivity indices were 6.05, 1.31, 0.35, 0.69 and 1.30 for the F. sellowiana (leaves and fruits), Q. castaneifolia, and A. paradoxum extracts and pyrimethamine, respectively. Moreover, the mice treated with F. sellowiana (leaves and fruits) achieved better results in terms of survival than the others (P < 0.05). Conclusion: The results of the current study indicate that methanol extract of F. sellowiana has significant anti-Toxoplasma activity. Further study should be conducted to investigate the potential bioactivity of this extract through bioactivity-guided fractionation

Antiparasitic Effects of Heracleum persicum and Foeniculum vulgare (Fruit) Essential Oils on Experimental Toxoplasmosis (In Vitro and In Vivo)

Background and purpose: There are few treatment options available for treatment of toxoplasmosis and effective drugs have serious toxic effects. In this study, the in vivo and in vitro anti-toxoplasma activities of Heracleum persicum and Foeniculum vulgare fruits essential oils were investigated. Materials and methods: In vitro, Vero cells were incubated with different concentrations of essential oils or pyrimethamine (positive control) and the cellular viability was determined. Next, Vero cells were infected with T. gondii (RH strain) and treated with agents. Then, the CC50, IC50, and selectivity index (SI) were calculated. Moreover, in vivo, the effect of oils on survival times of Balb/c mice infected with T. gondii were determined. Results: In vitro results showed that the oils exhibited less cell toxicity than pyrimethamine. The selective index was 2.94, 6.96, and 3.06 for Heracleum persicum, Foeniculum vulgare, and pyrimethamine, respectively. Also, the infected mice treated with F. vulgare-pyrimethamine showed a better survival rate than others (P<0.05). Conclusion: The H. persicum and F. vulgare essential oils showed anti-toxoplasmic activity in vitro and in vivo, but, combination therapy with F. vulgare and pyrimethamine showed a better survival time in mice infected with T. gondii. Therefore, F. vulgare may be a useful candidate in treatment of Toxoplasmosis. However, further studies are needed to investigate the fractions of this plant against T. gondii