Abstract
The effects of azithromycin treatment on the presence of Wolbachia endobacteria and on the embryogenesis and microfilariae production of Onchocerca volvulus were studied. In 2002, in an endemic area in Ghana, 37 onchocerciasis patients were treated for 6 weeks with azithromycin: 23 patients received 250 mg every day, and 14 took 1,200 mg once a week. After 6 and/or 12 months, all palpable worm nodules were extirpated from 31 treated and nine additional untreated patients, and the presence of Wolbachia and embryogenesis were assessed by immunohistology. In nodules taken 6 months after treatment with either dose and 12 months after 1,200 mg/week, the Wolbachia loads of the worms were not different from those of untreated worms. However, 12 months after the 250-mg/day azithromycin regimen, significantly less female worms (65% compared to 92% untreated ones) presented many Wolbachia, although the reduction was less pronounced than observed in other studies after treatment with doxycycline. Embryogenesis and microfilariae production were not reduced. It is concluded that azithromycin administered alone for 6 weeks at 250 mg/day or 1,200 mg/week is not suitable for treatment of human onchocerciasis. But daily azithromycin should be studied in combination with other drugs and with other doses.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- APR:
-
O. volvulus aspartic protease
- DiWSP:
-
D. immitis Wolbachia surface protein
- mf:
-
microfilaria(e)
References
Albiez EJ, Büttner DW, Duke BO (1988) Diagnosis and extirpation of nodules in human onchocerciasis. Trop Med Parasitol 39:331–346
Awadzi K, Addy ET, Opoku NO, Plenge-Bönig A, Büttner DW (1995a) The chemotherapy of onchocerciasis XX: ivermectin in combination with albendazole. Trop Med Parasitol 46:213–220
Awadzi K, Hero M, Opoku NO, Addy ET, Büttner DW, Ginger CD (1995b) The chemotherapy of onchocerciasis XVIII. Aspects of treatment with suramin. Trop Med Parasitol 46:19–26
Awadzi K, Attah SK, Addy ET, Opoku NO, Quartey BT (1999) The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients. Trans R Soc Trop Med Hyg 93:189–194
Basanez MG, Pion SD, Churcher TS, Breitling LP, Little MP, Boussinesq M (2006) River blindness: a success story under threat? PLoS Med 3:e371
Bazzocchi C, Jamnongluk W, O’Neill SL, Anderson TJ, Genchi C, Bandi C (2000) wsp gene sequences from the Wolbachia of filarial nematodes. Curr Microbiol 41:96–100
Bourguinat C, Pion SD, Kamgno J, Gardon J, Duke BO, Boussinesq M, Prichard RK (2007) Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment. PLoS Negl Trop Dis 1:e72
Büttner DW, Albiez EJ, von Essen J, Erichsen J (1988) Histological examination of adult Onchocerca volvulus and comparison with the collagenase technique. Trop Med Parasitol 39:390–417
Coles GC, Rhodes AC, Wolstenholme AJ (2005) Rapid selection for ivermectin resistance in Haemonchus contortus. Vet Parasitol 129:345–347
Debrah AY, Mand S, Specht S, Marfo-Debrekyei Y, Batsa L, Pfarr K, Larbi J, Lawson B, Taylor M, Adjei O, Hoerauf A (2006) Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis. PLOS Pathogens 2(9):e92
Debrah A, Mand S, Marfo-Debrekyei Y, Batsa L, Pfarr K, Buttner M, Adjei O, Buttner DW, Hoerauf A (2007) Macrofilaricidal activity after four weeks doxycycline treatment of Wuchereria bancrofti. Trop Med Int Health 12:1433–1441
Eng JK, Blackhall WJ, Osei-Atweneboana MY, Bourguinat C, Galazzo D, Beech RN, Unnasch TR, Awadzi K, Lubega GW, Prichard RK (2006) Ivermectin selection on beta-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus. Mol Biochem Parasitol 150:229–235
Foster J, Ganatra M, Kamal I, Ware J, Makarova K, Ivanova N, Bhattacharyya A, Kapatral V, Kumar S, Posfai J, Vincze T, Ingram J, Moran L, Lapidus A, Omelchenko M, Kyrpides N, Ghedin E, Wang S, Goltsman E, Joukov V, Ostrovskaya O, Tsukerman K, Mazur M, Comb D, Koonin E, Slatko B (2005) The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode. PLoS Biol 3:e121
Ghedin E, Wang S, Spiro D, Caler E, Zhao Q, Crabtree J, Allen JE, Delcher AL, Guiliano DB, Miranda-Saavedra D, Angiuoli SV, Creasy T, Amedeo P, Haas B, El-Sayed NM, Wortman JR, Feldblyum T, Tallon L, Schatz M, Shumway M, Koo H, Salzberg SL, Schobel S, Pertea M, Pop M, White O, Barton GJ, Carlow CK, Crawford MJ, Daub J, Dimmic MW, Estes CF, Foster JM, Ganatra M, Gregory WF, Johnson NM, Jin J, Komuniecki R, Korf I, Kumar S, Laney S, Li BW, Li W, Lindblom TH, Lustigman S, Ma D, Maina CV, Martin DM, McCarter JP, McReynolds L, Mitreva M, Nutman TB, Parkinson J, Peregrin-Alvarez JM, Poole C, Ren Q, Saunders L, Sluder AE, Smith K, Stanke M, Unnasch TR, Ware J, Wei AD, Weil G, Williams DJ, Zhang Y, Williams SA, Fraser-Liggett C, Slatko B, Blaxter ML, Scott AL (2007) Draft genome of the filarial nematode parasite Brugia malayi. Science 317:1756–1760
Hoerauf A, Volkmann L, Hamelmann C, Adjei O, Autenrieth IB, Fleischer B, Büttner DW (2000a) Endosymbiotic bacteria in worms as targets for a novel chemotherapy in filariasis. Lancet 355:1242–1243
Hoerauf A, Volkmann L, Paehle K, Schmetz C, Autenrieth I, Büttner DW, Fleischer B (2000b) Targeting of Wolbachia in Litomosoides sigmodontis: comparison of tetracycline with chloramphenicol, macrolides and ciprofloxacin. Trop Med Int Health 5:275–279
Hoerauf A, Mand S, Adjei O, Fleischer B, Büttner DW (2001) Depletion of Wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet 357:1415–1416
Hoerauf A, Mand S, Volkmann L, Büttner M, Marfo-Debrekyei Y, Taylor M, Adjei O, Büttner DW (2003) Doxycycline in the treatment of human onchocerciasis: kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms. Microbes Infect 5:261–273
Hoerauf A, Specht S, Büttner M, Pfarr K, Mand S, Fimmers R, Marfo Y, Konadu P, Debrah A, Bandi C, Brattig N, Albers A, Larbi J, Batsa L, Taylor M, Adjei O, Büttner DW (2007) Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis. Med Microbiol Immunol DOI 10.1007/s00430-00007-00062-00431
Jolodar A, Fischer P, Büttner DW, Miller DJ, Schmetz C, Brattig NW (2004) Onchocerca volvulus: expression and immunolocalization of a nematode cathepsin D-like lysosomal aspartic protease. Exp Parasitol 107:145–156
Kutin K, Kruppa TF, Brenya R, Garms R (2004) Efficiency of Simulium sanctipauli as a vector of Onchocerca volvulus in the forest zone of Ghana. Med Vet Entomol 18:167–173
Little MP, Breitling LP, Basanez MG, Alley ES, Boatin BA (2004) Association between microfilarial load and excess mortality in onchocerciasis: an epidemiological study. Lancet 363:1514–1521
Pfarr K, Hoerauf A (2005) The annotated genome of Wolbachia from the filarial nematode Brugia malayi. What it means for progress in anti-filarial medicine. PLoS Med 2:110
Rao R, Weil GJ (2002) In vitro effects of antibiotics on Brugia malayi worm survival and reproduction. J Parasitol 88:605–611
Richards FO Jr., Amann J, Arana B, Punkosdy G, Klein R, Blanco C, Lopez B, Mendoza C, Dominguez A, Guarner J, Maguire JH, Eberhard M (2007) No depletion of Wolbachia from Onchocerca volvulus after a short course of rifampin and/or azithromycin. Am J Trop Med Hyg 77:878–882
Sendi PP, Craig BA, Meier G, Pfluger D, Gafni A, Opravil M, Battegay M, Bucher HC (1999) Cost-effectiveness of azithromycin for preventing Mycobacterium avium complex infection in HIV-positive patients in the era of highly active antiretroviral therapy. The Swiss HIV Cohort Study. J Antimicrob Chemother 44:811–817
Turner JD, Mand S, Debrah AY, Muehlfeld J, Pfarr K, McGarry HF, Adjei O, Taylor MJ, Hoerauf A (2006) A randomized, double-blind clinical trial of a 3-week course of doxycycline plus albendazole and ivermectin for the treatment of Wuchereria bancrofti infection. Clin Infect Dis 42:1081–1089
WHO (1995) Onchocerciasis and its control. WHO Tech Rep Ser 852:1–103
Acknowledgements
We thank the study participants and the District Health Management team of Upper Denkyira district for their cooperation. We are obliged to Prof. Dr. Claudio Bandi, Milan, for the DiWSP anti-serum and PD Dr. Norbert Brattig, Hamburg, for the APR anti-serum. Pfizer Inc., Karlsruhe, Germany generously provided Zithromax® 250 and Ultreon® tablets. We acknowledge the technical assistance by Ingeborg Albrecht and Marlis Badusche, Hamburg, Germany.
Funding
We are grateful for financial support from the European Commission (EU-grants ICA4-CT-2002-10051 and INCO-CT-2006-032321) and the VW foundation (grant 1/81306).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hoerauf, A., Marfo-Debrekyei, Y., Büttner, M. et al. Effects of 6-week azithromycin treatment on the Wolbachia endobacteria of Onchocerca volvulus . Parasitol Res 103, 279–286 (2008). https://doi.org/10.1007/s00436-008-0964-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-008-0964-x