TITLE:
Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis
AUTHORS:
Helieh S. Oz
KEYWORDS:
Toxoplasma, Atovaquone, Diclazuril, Synergistic, Protection, Fetal Maternal, Congenital Toxoplasmosis, Pregnancy, Gastroenteritis
JOURNAL NAME:
International Journal of Clinical Medicine,
Vol.5 No.15,
August
11,
2014
ABSTRACT: Over 1 billion people
globally are estimated to be infected with Toxoplasma gondii with severe
or unknown consequences and no safe and effective therapies are available
against congenital or persistent chronic infection. We propose that atovaquone
and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods: 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. Results:
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 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 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. Conclusions: 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.