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Artemether Treatment of Prepatent Schistosoma japonicum Induces Resistance to Reinfection in Association with Reduced Pathology

Artemether (ART) is a well-described antimalarial with efficacy against juvenile schistosomes, with 7-day-old schistosomula being particularly susceptible. Both ART-affected worms and parasites developing from irradiated cercariae die at similar times after infection. Our aim was to determine if ART treatment of prepatent schistosomiasis japonica may result in the generation of a protective immune response. Female CBA mice were treated with a single dose of ART at defined time points after percutaneous infection with a virulent Chinese mainland strain of Schistosoma japonicum. Half of the mouse cohorts were subjected to homologous parasite strain reinfection after drug treatment to assess protective effects of ART therapy. Two independent trials demonstrated that a statistically significant (58% and 50%) reduction in challenge worm burden occurred after reinfection of those mice treated with ART at two weeks p.i. A reduction in the IL-4 response to soluble worm antigen preparation (SWAP) was also seen in ART-treated mice but with no correlation to reinfection resistance. In the Chinese mainland strain used, ART treatment of prepatent infection at the appropriate time point induced resistance to reinfection. There was also an anti-pathology effect observed in ART-treated mice that remained significant after reinfection.

Received October 7, 2007. Accepted for publication February 17, 2008.

Acknowledgments: Paul Bartley was supported by a Sir Gustav Nossal Medical Postgraduate Scholarship from the National Health and Medical Research Council (NHMRC) of Australia and a laboratory maintenance grant from the Cooperative Research Centre for Vaccine Technology (CRC-VT), Australia. Financial support from the NHMRC of Australia (DPM and MKJ), Howard Hughes Medical Institute (YL) and the Wellcome Trust (ICRGS Award-DPM) is gratefully acknowledged.

^* Address correspondence to Paul B. Bartley, Molecular Parasitology Laboratory, Queensland Institute of Medical Research, Herston Road, Herston, 4029, Australia. E-mail: paul.bartley{at}qml.com.au

Authors’ addresses: Paul B. Bartley, Amber Glanfield, Yuesheng Li, Mary Duke, Malcolm Jones, and Donald McManus, Molecular Parasitology Laboratory, Queensland Institute of Medical Research, Herston Road, Herston, 4029, Australia, Tel: +61 +7 +33620401, Fax: +61 +7 +3362 0104, E-mail: paul.bartley{at}qml.com.au. Danielle Stanisic, Department of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.