Abstract
Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams. This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis.
Highlights
Over 1 billion people globally are estimated to be infected with Toxoplasma gondii, a widespread cause of foodborne disease and congenital toxoplasmosis of which diseases include severe health complications which are endemic in rural areas [1]
Dams were divided into groups and received 1) atovaquone monotherapy, 2) diclazuril monotherapy, 3) atovaquone + diclazuril combined, or 4) sham treatment
Treatments overall were effective in groups infected with lower dose (300) as manifested with moderate toxoplasmosis with minor differences between monotherapies
Summary
Over 1 billion people globally are estimated to be infected with Toxoplasma gondii, a widespread cause of foodborne disease and congenital toxoplasmosis of which diseases include severe health complications which are endemic in rural areas [1]. Congenital toxoplasmosis occurs when the fetus of a seronegative woman or animal becomes infected with organism or a clinically quiescent maternal infection reactivates, typically associated with pregnancy immunosuppression [3]. Toxoplasmosis can manifest as gastrointestinal complications, spontaneous abortion, intrauterine fetal death, preterm delivery, or severe fetal malformations, including ocular, cerebral syndromes, and encephalitis [6]. It is considered as the third most common foodborne cause of hospitalization and death in patients [1] [7] frequently misdiagnosed or under-diagnosed [8]. From 1,500,000 predicted cases of toxoplasmosis, only small fraction (15%) is clinically detected each year in USA [9]
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