Adjunctive bradyzoite-directed therapy for reducing complications of congenital toxoplasmosis

Med Hypotheses. 2019 Dec:133:109376. doi: 10.1016/j.mehy.2019.109376. Epub 2019 Aug 19.

Abstract

Congenital toxoplasmosis is caused by in utero infection of the fetus with the intracellular parasite Toxoplasma gondii. Upon infection, the parasite forms life-long cysts in fetal brain and eyes which are resistant to the currently accepted therapy of pyrimethamine and sulfadiazine. These cysts commonly reactivate later in life causing chorioretinitis and visual impairment, and rarely cause neurological complications. I hypothesize that adjunctive, bradyzoite-directed therapies have the potential to alleviate a significant burden of disease by reducing cyst burden in neonatal brain and eyes. Atovaquone is perhaps the most promising drug for further evaluation given its low side-effect profile, established safety, and efficacy in animal models reducing cyst burden. Very limited observational data in humans suggests atovaquone may prevent Toxoplasma-associated chorioretinitis recurrence. Clinical trials are needed to evaluate it and other potential drugs as adjunctive treatment in congenital toxoplasmosis.

MeSH terms

  • Animals
  • Antiprotozoal Agents / pharmacology
  • Antiprotozoal Agents / therapeutic use*
  • Atovaquone / pharmacology
  • Atovaquone / therapeutic use
  • Brain / parasitology
  • Chorioretinitis / drug therapy*
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Eye / parasitology
  • Humans
  • Infant
  • Infant, Newborn
  • Mice
  • Models, Biological
  • Recurrence
  • Spiramycin / pharmacology
  • Spiramycin / therapeutic use
  • Toxoplasma / drug effects*
  • Toxoplasma / growth & development
  • Toxoplasmosis, Animal / congenital
  • Toxoplasmosis, Animal / drug therapy
  • Toxoplasmosis, Cerebral / drug therapy*
  • Toxoplasmosis, Congenital
  • Toxoplasmosis, Ocular / drug therapy*

Substances

  • Antiprotozoal Agents
  • Spiramycin
  • Atovaquone