Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability.
The symbiosis of filarial nematodes and rickettsial Wolbachia endobacteria has been exploited as a target for antibiotic therapy of filariasis. Depletion of Wolbachia after tetracycline treatment results in filarial sterility because of interruption of embryogenesis and inhibits larval development and adult worm viability. The aim of this study was to investigate if antibiotic intervention of BALB/c mice infected with the rodent filaria Litomosoides sigmodontis with rifampicin or the combination of rifampicin and doxycycline can be used to shorten the treatment period. Both regimens, when given over a period of 14 days initiated with infection, were sufficient to deplete Wolbachia as evidenced by immunohistology and semiquantitative PCR. Worm development and filarial load were significantly reduced in experiments followed up until 63 days p.i. The therapy inhibited embryogenesis and led to filarial sterility. In contrast, treatment with doxycycline alone for 21 days led only to a modest reduction of Wolbachia, filarial growth retardation, worm viability and fertility. In conclusion, the combination of antirickettsial drugs could be used as a suitable tool to explore the minimum duration of therapy required for the depletion of Wolbachia in parasitized hosts subsequent to the onset of patency in human and animal filariasis and the prevention of adverse reactions in human infections.
Volkmann
Lars
L
Department of Helminthology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. lars_volkmann@hotmail.com
Fischer
Kerstin
K
Taylor
Mark
M
Hoerauf
Achim
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004318:Doxycycline / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D005368:Filariasis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005370:Filarioidea / Q000187:drug effects / Q000254:growth & development; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012288:Rickettsiaceae Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012293:Rifampin / Q000627:therapeutic use; D013559:Symbiosis / Q000187:drug effects; D020577:Wolbachia / Q000187:drug effects* / Q000254:growth & development
D000900:Anti-Bacterial Agents; D004318:Doxycycline; D012293:Rifampin