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.

The currently available anti-Toxoplasma agents have serious limitations. This systematic review was performed to evaluate drugs and new compounds used for the treatment of toxoplasmosis. Data was systematically collected from published papers on the efficacy of drugs/compounds used against Toxoplasma gondii (T. gondii) globally during 2006–2016. The searched databases were PubMed, Google Scholar, Science Direct, ISI Web of Science, EBSCO, and Scopus. One hundred and eighteen papers were eligible for inclusion in this systematic review, which were both in vitro and in vivo studies. Within this review, 80 clinically available drugs and a large number of new compounds with more than 39 mechanisms of action were evaluated. Interestingly, many of the drugs/compounds evaluated against T. gondii act on the apicoplast. Therefore, the apicoplast represents as a potential drug target for new chemotherapy. Based on the current findings, 49 drugs/compounds demonstrated in vitro half-maximal inhibitory concentration (IC50) values of below 1 μM, but most of them were not evaluated further for in vivo effectiveness. However, the derivatives of the ciprofloxacin, endochin-like quinolones and 1-[4-(4-nitrophenoxy) phenyl] propane-1-one (NPPP) were significantly active against T. gondii tachyzoites both in vitro and in vivo. Thus, these compounds are promising candidates for future studies. Also, compound 32 (T. gondii calcium-dependent protein kinase 1 inhibitor), endochin-like quinolones, miltefosine, rolipram abolish, and guanabenz can be repurposed into an effective anti-parasitic with a unique ability to reduce brain tissue cysts (88.7, 88, 78, 74, and 69%, respectively). Additionally, no promising drugs are available for congenital toxoplasmosis. In conclusion, as current chemotherapy against toxoplasmosis is still not satisfactory, development of well-tolerated and safe specific immunoprophylaxis in relaxing the need of dependence on chemotherapeutics is a highly valuable goal for global disease control. However, with the increasing number of high-risk individuals, and absence of a proper vaccine, continued efforts are necessary for the development of novel treatment options against T. gondii. Some of the novel compounds reviewed here may represent good starting points for the discovery of effective new drugs. In further, bioinformatic and in silico studies are needed in order to identify new potential toxoplasmicidal drugs.

Background: Felids (domestic and wild cats) are important in the epidemiology of the parasite Toxoplasma gondii because they are the only hosts that can excrete the environmentally resistant oocysts. We conducted a systematic review and meta-analysis to estimate the global prevalence of T. gondii in species of the family Felidae. Methods: We searched seven databases (PubMed, Embase, Google Scholar, ScienceDirect, Scopus, Proquest and Web of Science) for studies reporting seroprevalence of T. gondii in felids from 1967 to 31 December 2017. A total of 217 published papers, containing 223 datasets were eligible for inclusion in the meta-analysis, comprised 59,517 domestic and 2733 wild cats from 1967 to 2017. Results: The pooled global T. gondii seroprevalence was estimated to be 35% (95% CI: 32-38%) and 59% (95% CI: 56-63%) in domestic cats and wild felids, respectively, using random effects model. The seroprevalence was higher in Australia and Africa where the T. gondii seropositivity in domestic cats was 52% (95% CI: 15-89%) and 51% (95% CI: 20-81%), respectively. The lowest seroprevalence was estimated in Asia 27% (95% CI: 24-30%). The seroprevalence values for T. gondii in wild felids were 74% (95% CI: 62-83%) in Africa, 67% (95% CI: 23-111%) in Asia, 67% (95% CI: 58-75%) in Europe and 66% (95% CI: 41-91%) in South America. Conclusions: Our study provides the global prevalence of T. gondii in species of the family Felidae and is a source of information to aid public health workers in developing prevention plans.

Toxoplasmosis is one of the most prevalent infections in humans and animals caused by the intracellular protozoan parasite Toxoplasma gondii (T. gondii). Rodents, as intermediate and reservoir hosts, play a key role in the maintenance and transmission of T. gondii. They can be contaminated and maintain the parasite in the form of cysts in their bodies, demonstrating an infection source for their offsprings, predators (particularly felids), and other animals. Therefore, the present systematic review and meta-analysis study was carried out to evaluate the global seroprevalence of T. gondii in these mammals. For achieving the purpose of the current study, six English databases (PubMed, Science Direct, Web of Science, Scopus, ProQuest, and Google Scholar) were systematically searched for related studies from 1970 to 2018. Finally, a total of 52,372 records were screened, 105 records including 26,221 rodents were incorporated in the present study. By random effect models, the overall seroprevalence was calculated at 6% (95% CI = 6-7%), with the highest amount was observed in Africa (24%) and South America (18%), and the lowest amount in Europe (1%). The subgroup data analysis by gender manifested that the prevalence of Immunoglobulin G antibodies did not differ between genders (P > 0.05). Due to the significant heterogeneity, meta-regression models were applied based on serological techniques and continental regions; however, the obtained values were not statistically significant (P = 0.480 and P = 0.295, respectively). The present study revealed a relatively low level of T. gondii seroprevalence in rodents; however, if they were the main food source for their predators, they would cause high transmission of T. gondii.

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