Evaluation of Current and Emerging Antimalarial Medicines for Inhibition of Toxoplasma gondii Growth in Vitro

Joshua B. Radke, Jeremy N. Burrows, Daniel E. Goldberg, L. David Sibley

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Toxoplasma gondii is a common zoonotic infection of humans, and estimates indicate that 1-2 billion people are chronically infected. Although largely asymptomatic, chronic infection poses risk of serious disease due to reactivation should immunity decline. Current therapies for toxoplasmosis only control acute infection caused by actively proliferating tachyzoites but do not eradicate the chronic tissue cyst stages. As well, there are considerable adverse side effects of the most commonly used therapy of combined sulfadiazine and pyrimethamine. Targeting the folate pathway is also an effective treatment for malaria, caused by the related parasites Plasmodium spp., suggesting common agents might be used to treat both infections. Here, we evaluated currently approved and newly emerging medicines for malaria to determine if such compounds might also prove useful for treating toxoplasmosis. Surprisingly, the majority of antimalarial compounds being used currently or in development for treatment of malaria were only modestly effective at inhibiting in vitro growth of T. gondii tachyzoites. These findings suggest that many essential processes in P. falciparum that are targeted by antimalarial compounds are either divergent or nonessential in T. gondii, thus limiting options for repurposing of current antimalarial medicines for toxoplasmosis.

Original languageEnglish
Pages (from-to)1264-1274
Number of pages11
JournalACS Infectious Diseases
Volume4
Issue number8
DOIs
StatePublished - Aug 10 2018

Keywords

  • Apicomplexa
  • Medicines for Malaria Venture
  • antibiotics
  • bradyzoite
  • chronic infection
  • latency

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