Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis.

[congenital toxoplasmosis]

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 .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 .

Diseases
Validation

Diseases presenting "pain" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

adrenomyeloneuropathy

aniridia

aromatase deficiency

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital diaphragmatic hernia

congenital toxoplasmosis

cushing syndrome

cutaneous mastocytosis

cystinuria

dedifferentiated liposarcoma

dentin dysplasia

dracunculiasis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

fabry disease

familial mediterranean fever

focal myositis

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

junctional epidermolysis bullosa

kabuki syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

malignant atrophic papulosis

neuralgic amyotrophy

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

phenylketonuria

pleomorphic liposarcoma

primary hyperoxaluria type 1

proteus syndrome

pyomyositis

scrub typhus

sneddon syndrome

systemic capillary leak syndrome

thoracic outlet syndrome

trochlear dysplasia

typhoid

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

wolf-hirschhorn syndrome

This symptom has already been validated