Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms.
Recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of Onchocerca. Hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. Based on animal experiments, human onchocerciasis was treated with doxycycline, and preliminary observations published in 2001 in The Lancet showed sterility in female worms by depletion and marked reduction in symbiotic Wolbachia endobacteria from the filariae. Here, a detailed kinetic analysis of the features of the worms, following administration or not of doxycycline to the patients is reported. Sixty-three onchocerciasis patients in Ghana were treated with 100 mg doxycycline daily for 6 weeks and 2 or 6 months later with ivermectin. Onchocercomas were extirpated 2, 6, 11 and 18 months after the onset of treatment and the filariae were examined by immunohistology and PCR. The analysis showed: (i) progressive depletion of Wolbachia from adult worms and microfilariae by doxycycline over a period of 6 months; (ii) inhibition of embryogenesis by doxycycline after 6 months with respect to all embryo stages followed by decline in microfilariae after 11 months; (iii) reduction in spermatozoa in the female genital tract by doxycycline, whereas spermiogenesis was only partly reduced after 11 and 18 months; (iv) no relevant macro- or microfilaricidal activity; (v) depletion/marked reduction in endobacteria and inhibition of embryogenesis were sustained until 18 months after doxycycline and 12 months after co-administration of ivermectin; (vi) no severe adverse side effects were seen. Due to its long-lasting inhibition of embryogenesis, doxycycline presents an additional strategy for the treatment of onchocerciasis and control of Onchocerca microfilariae transmission. Extension of the existing registration will not require much time or high cost. Treatment of individual patients can be considered immediately.
Hoerauf
Achim
A
Department of Helminthology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany. hoerauf@bni.uni-hamburg.de
Mand
Sabine
S
Volkmann
Lars
L
Büttner
Marcelle
M
Marfo-Debrekyei
Yeboah
Y
Taylor
Mark
M
Adjei
Ohene
O
Büttner
Dietrich W
DW
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004318:Doxycycline / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007559:Ivermectin / Q000494:pharmacology; D008297:Male; D008842:Microfilariae / Q000187:drug effects / Q000254:growth & development; D017181:Onchocerca volvulus / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000472:pathogenicity; D009855:Onchocerciasis / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects; D016896:Treatment Outcome; D020577:Wolbachia / Q000187:drug effects* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007559:Ivermectin; D004318:Doxycycline