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30 August 2012

Atovaquone ameliorate gastrointestinal Toxoplasmosis complications in a pregnancy model

Helieh S. OzABCDEFG, Thomas TobinG

DOI: 10.12659/MSM.883342

Med Sci Monit 2012; 18(9): BR337-345

Abstract

Background: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis.
Material/Methods: Programmed pregnant mice were i.p. infected with 50–2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications.
Results: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and severe hepatitis (score 3.6±0.01 on scale 0 – normal to 4 – severe) with influx of inflammatory and plasma cells, multinucleated dysplastic hepatocytes and necrosis. In addition, dams expressed mild to severe pancreatitis with mononuclear cell invasion, loss of islets and necrosis. This was consistent with splenomegaly (X3 Fold), and massive infiltration of epithelioid cells and loss of germinal structure. Colon became significantly shortened in length (p<0.01) with semi-normal content. Pathological manifestation included, shortening of crypts with numerous microabscess formations, infiltration of lymphocytes, and macrophages. The severe clinical complications led to abortion (50%), early birth (25%) or still birth (25%) consistent with the high dose of Tachyzoites inoculation. Atovaquone treatment partially but significantly protected the dams from the severity of hepatitis, splenomegaly, colitis, myocarditis, and pain related responses as well as fetal demise.
Conclusions: This is a valuable model for therapeutic evaluation of feto-maternal Toxoplasmosis and gastrointestinal complications. Atovaquone protects dams and their fetuses against some infectious/inflammatory aspects of the disease.

Keywords: Mice, Hyperalgesia - prevention & control, Hepatitis - prevention & control, Gastrointestinal Tract - pathology, Disease Models, Animal, Atovaquone - therapeutic use, Anti-Infective Agents - therapeutic use, Animals, Analysis of Variance, Pancreatitis - prevention & control, Pregnancy, Toxoplasmosis, Congenital - pathology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750