title: Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms: revival of an old drug.
abstract: BACKGROUND
  It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations.
  
  
  METHODS
  We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo.
  
  
  RESULTS
  We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo.
  
  
  CONCLUSIONS
  Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launched.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. jennifer.keiser@unibas.ch
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
authors.forename: Lucienne
authors.initials: L
authors.lastname: Tritten
authors.forename: Angelika
authors.initials: A
authors.lastname: Silbereisen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Speich
authors.forename: Roberto
authors.initials: R
authors.lastname: Adelfio
authors.forename: Mireille
authors.initials: M
authors.lastname: Vargas
mesh_terms: D000722:Ancylostoma / Q000187:drug effects; D000724:Ancylostomiasis / Q000188:drug therapy* / Q000469:parasitology; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D017221:Necator americanus / Q000187:drug effects; D009332:Necatoriasis / Q000188:drug therapy* / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D011716:Pyrantel Pamoate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D014257:Trichuriasis / Q000188:drug therapy* / Q000469:parasitology; D014258:Trichuris / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D011716:Pyrantel Pamoate; C037225:oxantel pamoate
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