Skip to main content
Log in

Efficacy of 2- and 4-week rifampicin treatment on the Wolbachia of Onchocerca volvulus

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

The microfilaricidal and temporarily sterilizing drug ivermectin is used for mass treatment of filarial infections. Filariae containing Wolbachia endobacteria can also be treated by the antibiotic doxycycline. The loss of Wolbachia results in sterilization of Onchocerca volvulus and macrofilaricidal effects. Besides doxycycline, other antibiotics may be effective in depleting Wolbachia. A preliminary study on the effects of rifampicin on the endobacteria, embryogenesis and microfilariae production of O. volvulus was carried out in the year 2000 in Ghana. Twenty-six onchocerciasis patients were treated for 2 or 4 weeks with 10 mg/kg/day rifampicin. From 17 treated and nine untreated patients, all palpable nodules were extirpated 1 or 18 months after the start of the study and examined for Wolbachia and embryogenesis using immunohistology. One and 18 months after rifampicin treatment, the proportion of Wolbachia-positive worms was significantly reduced compared to the untreated group. In patients treated 4 weeks with rifampicin, only 21% and 18% of living female filariae contained Wolbachia after 1 and 18 months, respectively, compared to 92% in the untreated patients. The reduction of Wolbachia after 2 weeks rifampicin was less but also significant. Embryogenesis and microfilariae production were reduced after 4 weeks rifampicin treatment, rendering rifampicin an antibiotic with anti-wolbachial efficacy in human onchocerciasis. This treatment is less efficient than treatment with 6 weeks doxycycline, but might be an alternative for cases that cannot be treated with doxycycline, e.g. children, or might be further developed for combination therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

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

    PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Basanez MG, Pion SD, Churcher TS, Breitling LP, Little MP, Boussinesq M (2006) River blindness: a success story under threat? PLoS Med 3:e371

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Coles GC, Rhodes AC, Wolstenholme AJ (2005) Rapid selection for ivermectin resistance in Haemonchus contortus. Vet Parasitol 129:345–347

    Article  PubMed  CAS  Google Scholar 

  • Hoerauf A, Volkmann L, Hamelmann C, Adjei O, Autenrieth IB, Fleischer B, Büttner DW (2000) Endosymbiotic bacteria in worms as targets for a novel chemotherapy in filariasis. Lancet 355:1242–1243

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Hoerauf A, Mand S, Volkmann L, Buttner 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

    Article  PubMed  CAS  Google Scholar 

  • Hoerauf A, Specht S, Buttner M, Pfarr K, Mand S, Fimmers R, Marfo-Debrekyei Y, Konadu P, Debrah AY, Bandi C, Brattig N, Albers A, Larbi J, Batsa L, Adjei O, Buttner DW (2007) Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study. Med Microbiol Immunol 197:295–311

    Article  PubMed  Google Scholar 

  • Jolodar A, Fischer P, Buttner 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

    Article  PubMed  CAS  Google Scholar 

  • Kose M, Kozan E, Sevimli FK, Eser M (2007) The resistance of nematode parasites in sheep against anthelmintic drugs widely used in Western Turkey. Parasitol Res 101:563–567

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Soutello RG, Seno MC, Amarante AF (2007) Anthelmintic resistance in cattle nematodes in northwestern Sao Paulo State, Brazil. Vet Parasitol 148:360–364

    Article  PubMed  CAS  Google Scholar 

  • Taylor MJ, Makunde W, McGarry HF, Mand S, Hoerauf A (2003) Doxycycline treatment of Wuchereria bancrofti: a double-blind placebo-controlled trial. Am J Trop Med Hyg 69:250, (Suppl)

    Google Scholar 

  • Townson S, Tagboto S, McGarry HF, Egerton GL, Taylor MJ (2006) Onchocerca parasites and Wolbachia endosymbionts: evaluation of a spectrum of antibiotic types for activity against Onchocerca gutturosa in vitro. Filaria J 5:4

    Article  PubMed  Google Scholar 

  • Van Zeveren AM, Casaert S, Alvinerie M, Geldhof P, Claerebout E, Vercruysse J (2007) Experimental selection for ivermectin resistance in Ostertagia ostertagi in cattle. Vet Parasitol 150:104–110

    Article  PubMed  Google Scholar 

  • Vickers M, Venning M, McKenna PB, Mariadass B (2001) Resistance to macrocyclic lactone anthelmintics by Haemonchus contortus and Ostertagia circumcincta in sheep in New Zealand. N Z Vet J 49:101–105

    PubMed  CAS  Google Scholar 

  • Volkmann L, Fischer K, Taylor M, Hoerauf A (2003) Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability. TM IH Trop Med Int Health 8:392–401

    Article  CAS  Google Scholar 

  • WHO (1995) Onchocerciasis and its control. WHO Tech Rep Ser 852:1–103

    Google Scholar 

Download references

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 WSP anti-serum and PD Dr. Norbert Brattig, Hamburg, for the APR antibody. We acknowledge the technical assistance by Ingeborg Albrecht and Marlis Badusche, Hamburg and we thank Dr. Marcelle Büttner, Hamburg, for the wound treatment after the nodulectomies. We are grateful for the 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

Authors

Corresponding author

Correspondence to Sabine Specht.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Specht, S., Mand, S., Marfo-Debrekyei, Y. et al. Efficacy of 2- and 4-week rifampicin treatment on the Wolbachia of Onchocerca volvulus . Parasitol Res 103, 1303–1309 (2008). https://doi.org/10.1007/s00436-008-1133-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-008-1133-y

Keywords

Navigation