Brugia malayi: Effects of nitazoxanide and tizoxanide on adult worms and microfilariae of filarial nematodes.
There is an urgent need for safe and effective antifilarials. Prior studies have shown that the nitazoxanide (NTZ) exhibits broad activity against anaerobic bacteria, protozoa, and certain intestinal helminths. We examined the effects of NTZ and tizoxanide (TZ) on Brugia malayi nematodes in vitro and in vivo. In vitro, NTZ and TZ reduced worm motility and viability in a dose-dependent manner. Worm viability was reduced by 50% with both compounds at 2.5 and 20 microg/ml killed adult worms. NTZ or TZ (5 microg/ml) significantly reduced microfilaria release. These compounds blocked worm's embryogenesis, and decreased microfilarial motility and viability. Treated worms had damaged cuticles and abnormal mitochondria. Wolbachia were not cleared by NTZ or TZ treatment. Neither NTZ nor TZ cleared adult worms or microfilariae in infected gerbils. These results show that NTZ and TZ have potent effects on B. malayi nematodes in vitro. However, they were not effective in vivo.
Rao
Ramakrishna U
RU
Department of Internal Medicine, Infectious Diseases Division, Washington University School of Medicine, St. Louis, MO 63110, USA. rrao@wustl.edu
Huang
Yuefang
Y
Fischer
Kerstin
K
Fischer
Peter U
PU
Weil
Gary J
GJ
D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017178:Brugia malayi / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005260:Female; D005368:Filariasis / Q000188:drug therapy* / Q000469:parasitology; D005849:Gerbillinae; D008297:Male; D008842:Microfilariae / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009574:Nitro Compounds; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000977:Antiparasitic Agents; D009574:Nitro Compounds; D013844:Thiazoles; C104067:tizoxanide; C041747:nitazoxanide