In vitro praziquantel test capable of detecting reduced in vivo efficacy in Schistosoma mansoni human infections.
Although great reductions in human schistosomiasis have been observed after praziquantel (PZQ) mass drug administration (MDA), some individuals remain infected after multiple treatments. Many MDA programs now require monitoring for drug efficacy as a key component. No molecular tools for PZQ resistance currently exist and investigations into the dose of PZQ required to kill 50% of adult worms in vivo (ED(50)) present ethical, logistical, and temporal restraints. We, therefore, assessed the feasibility and accuracy of a rapid, inexpensive in vitro PZQ test in the laboratory and directly in the field in Uganda under MDA in conjunction with highly detailed infection intensity, clearance, and reinfection data. This test strongly differentiated between subsequently cleared and uncleared infections as well as differences between parasite populations pre- and post-PZQ treatments, advocating its use for on-the-spot monitoring of PZQ efficacy in natural foci. After only a few treatments, uncleared parasites were identified to be phenotypically different from drug-sensitive parasites, emphasizing the urgent need for monitoring of these repeatedly PZQ-treated populations.
Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, United Kingdom. poppy.lamberton@imperial.ac.uk
Poppy H L
PH
Lamberton
Sarah C
SC
Hogan
Narcis B
NB
Kabatereine
Alan
A
Fenwick
Joanne P
JP
Webster
D000818:Animals; D002648:Child; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D014454:Uganda / Q000453:epidemiology
D011223:Praziquantel