Drug Resistance in Toxoplasma gondii

Abstract

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.

Copaifera spp. oleoresins impair Toxoplasma gondii infection in both human trophoblastic cells and human placental explants

“…In the context of congenital transmission, when a woman gets the infection during pregnancy, recommended drugs for treatment are limited to a combination of sulfadiazine plus pyrimethamine (SDZ + PYR) and spiramycin 8 , 19 , 20 , 24 . Unfortunately, the use of these drugs has been associated with severe side effects and uncommon reactions in both mother and child 3 , 27 , 56 . Additionally, several independent studies have shown that T. gondii has an exceptional adaptive potential, which has led to the development of drug-resistant parasites 56 – 58 .…”

Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs

“…However, it has been observed that about 40% of patients were forced to stop therapy due to low tolerance and serious adverse effects (Porter and Sande, 1992;McLeod et al, 2006;Rajapakse et al, 2013). In addition, drug resistance cases are being reported in some cases of toxoplasmosis (Montazeri et al, 2018). Also, there are no approved therapies for the eradication of the encysted bradyzoite form.…”

WITHDRAWN: Sero-epidemiology of Toxoplasma gondii and risk factors among pregnant women in Africa

“…Human can be infected with T. gondii through one of three ways: 1) by eating raw or undercooked meat containing T. gondii tissue cysts or eating food that has been cross-contaminated with raw/undercooked meat; 2) by ingesting oocysts from soil (through gardening, handling/eating unwashed vegetables, or infected cat feces); or 3) by acquiring congenital infection through the placenta [4,5] when a woman gets an infection during pregnancy [6,7] In most cases, infection in humans is asymptomatic or mild symptoms including malaise, swelling of lymph nodes and fever [8], however, when infection occurs in pregnant women several health problems can affect the fetuses, including mental retardation, blindness, epilepsy, abortion and death [1,9]. Moreover, In a systematic review and meta-analysis, it was reported that T. gondii causes severe encephalitis via acute infection or reactivation of latent infection among immune-suppressed individuals, including those with acquired immunodeficiency syndrome (AIDS), immunosuppressive cancer, and transplant recipients on immunosuppressive drugs [10].…”