Macrofilaricidal activity of tetracycline against the filarial nematode Onchocerca ochengi: elimination of Wolbachia precedes worm death and suggestsa dependent relationship

Filarial nematodes are important and widespread parasites of animals and hu mans. We have been using the African bovine parasite Onchocerca ochengi as a chemotherapeutic model for O. volvulus, the causal organism of 'river bli ndness' in humans, for which there is no safe and effective drug lethal to adult worms. Here we report that the antibiotic, oxytetracycline is macrofi laricidal against O. ochengi. In a controlled trial in Cameroon, all adult worms (as well as microfilariae) were killed, and O. ochengi intradermal no dules resolved, by nine months' post-treatment in cattle treated intermitte ntly for six months. Adult worms removed from concurrent controls remained fully viable and reproductively active. By serial electron-microscopic exam ination, the macrofilaricidal effects were related to the elimination of in tracellular micro-organisms, initially abundant. Analysis of a fragment of the 16S rRNA gene from the O. ochengi micro-organisms confirmed them to be Wolbachia organisms of the order Rickettsiales, and showed that the sequenc e differed in only one nucleotide in 858 from the homologous sequence of th e Wolbachia organisms of O. volvulus. These data are, to our knowledge, the first to show that antibiotic therapy can be lethal to adult filariae. The y suggest that tetracycline therapy is likely to be macrofilaricidal agains t O. volvulus infections in humans and, since similar Wolbachia organisms o ccur in a number of other filarial nematodes, against those infections too. In that the elimination of I Wolbachia preceded the resolution of the fila rial infections, they suggest that in O. ochengi at least, the Wolbachia or ganisms play an essential role in the biology and metabolism of the filaria l worm.