Medical Microbiology and Immunology

, Volume 192, Issue 4, pp 211–216 | Cite as

Doxycycline as a novel strategy against bancroftian filariasis—depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production

  • Achim HoeraufEmail author
  • Sabine Mand
  • Kerstin Fischer
  • Thomas Kruppa
  • Yeboah Marfo-Debrekyei
  • Alexander Yaw Debrah
  • Kenneth M. Pfarr
  • Ohene Adjei
  • Dietrich W. Büttner
Original Investigation


Chemotherapy of onchocerciasis by doxycycline, which targets symbiotic Wolbachia endobacteria, has been shown to result in a long-term sterility of adult female worms and corresponding absence of microfilariae. It represents an additional chemotherapeutic approach. The aim of this study was to determine whether a similar regimen would also show efficacy against Wuchereria bancrofti. Ghanaian individuals (n=93) with lymphatic filariasis and a minimum microfilaremia of 40 microfilariae/ml were included in a treatment study consisting of four arms: (1) doxycycline 200 mg/day for 6 weeks; (2) doxycycline as in (1), followed by a single dose of ivermectin after 4 months; (3) ivermectin only; or (4) no treatment during observation period of 1 year (ivermectin at the end of the study). Doxycycline treatment resulted in a 96% loss of Wolbachia, as determined by real time PCR from microfilariae. After 12 months, doxycycline had led to a 99% reduction of microfilaremia when given alone, and to a complete amicrofilaremia together with ivermectin. In contrast, after ivermectin treatment alone a significant presence of microfilariae remained (9% compared to pretreatment), as known from other studies. This study shows that doxycycline is also effective in depleting Wolbachia from W. bancrofti. It is likely that the mechanism of doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in bancroftian filariasis, such as tropical pulmonary eosinophilia and microfiluria.


Lymphatic filariasis Wuchereria bancroft Wolbachia Doxycycline Ivermectin 



We would like to thank the individuals of the district health management in East Nzema, Western Region, Ghana, for their cooperation. We would like to thank Mr. John Larbi, Dr. Matthias Grade, and Dr. Yeetey Enuameh for excellent support. Dr. Hoerauf acknowledges financial support by the German Research Foundation (DFG-grant Ho 2009/1-3); the European Commission (grant ICA4-CT-2002-10051), and Caritas Charity.


  1. 1.
    Taylor M, Hoerauf A (1999) Wolbachia bacteria of filarial nematodes. Parasitol Today 15:437–442CrossRefPubMedGoogle Scholar
  2. 2.
    Bandi C, Trees AJ, Brattig NW (2001) Wolbachia in filarial nematodes: evolutionary aspects and implications for the pathogenesis and treatment of filarial diseases. Vet Parasitol 98:215–238CrossRefPubMedGoogle Scholar
  3. 3.
    Taylor MJ, Hoerauf A (2001) A new approach to the treatment of filariasis. Curr Opin Infect Dis 14:727–731PubMedGoogle Scholar
  4. 4.
    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 357:1415–1416PubMedGoogle Scholar
  5. 5.
    Hoerauf A, Walter RD, Remme H, Lazdins J, Fleischer B (2001) Call to consolidate achievements for onchocerciasis and lymphatic filariasis control. Trends Parasitol 17:566–567PubMedGoogle Scholar
  6. 6.
    Hoerauf A, Adjei O, Büttner DW (2002) Antibiotics for the treatment of onchocerciasis and other filarial infections. Curr Opin Invest Drugs 3:533–537Google Scholar
  7. 7.
    Ottesen EA (2000) The global programme to eliminate lymphatic filariasis. Trop Med Int Health 5:591–594PubMedGoogle Scholar
  8. 8.
    Molyneux DH, Taylor MJ (2001) Current status and future prospects of the Global Lymphatic Filariasis Programme. Curr Opin Infect Dis 14:155–159PubMedGoogle Scholar
  9. 9.
    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 355:1242–1243PubMedGoogle Scholar
  10. 10.
    Fischer P, Liu X, Lizotte-Waniewski M, Kamal IH, Ramzy RM, Williams SA (1999) Development of a quantitative, competitive polymerase chain reaction-enzyme-linked immunosorbent assay for the detection of Wuchereria bancrofti DNA. Parasitol Res 85:176–183PubMedGoogle Scholar
  11. 11.
    Dreyer G, Amaral F, Noroes J, Medeiros Z, Addiss D (1995) A new tool to assess the adulticidal efficacy in vivo of antifilarial drugs for bancroftian filariasis. Trans R Soc Trop Med Hyg 89:225–226PubMedGoogle Scholar
  12. 12.
    Noroes J, Addiss D, Amaral F, Coutinho A, Medeiros Z, Dreyer G (1996) Occurrence of living adult Wuchereria bancrofti in the scrotal area of men with microfilaraemia. Trans R Soc Trop Med Hyg 90:55–56PubMedGoogle Scholar
  13. 13.
    Faris R, Hussain O, El Setouhy M, Ramzy RM, Weil GJ (1998) Bancroftian filariasis in Egypt: visualization of adult worms and subclinical lymphatic pathology by scrotal ultrasound. Am J Trop Med Hyg 59:864–867PubMedGoogle Scholar
  14. 14.
    More SJ, Copeman DB (1990) A highly specific and sensitive monoclonal antibody-based ELISA for the detection of circulating antigen in bancroftian filariasis. Trop Med Parasitol 41:403–406PubMedGoogle Scholar
  15. 15.
    Simonsen PE, Dunyo SK (1999) Comparative evaluation of three new tools for diagnosis of bancroftian filariasis based on detection of specific circulating antigens. Trans R Soc Trop Med Hyg 93:278–282PubMedGoogle Scholar
  16. 16.
    Weil GJ, Lammie PJ, Weiss N (1997) The ICT filariasis test: a rapid-format antigen test for diagnosis of Bancroftian filariasis. Parasitol Today 13:401–404CrossRefGoogle Scholar
  17. 17.
    Plaisier AP, Stolk WA, van Oortmarssen GJ, Habbema JD (2000) Effectiveness of annual ivermectin treatment for Wuchereria bancrofti infection. Parasitol Today 16:298–302CrossRefPubMedGoogle Scholar
  18. 18.
    Dunyo SK, Nkrumah FK, Simonsen PE (2000) A randomized double-blind placebo-controlled field trial of ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana. Trans R Soc Trop Med Hyg 94:205–211PubMedGoogle Scholar
  19. 19.
    Bradley DJ, Warhurst DC (1997) Guidelines for the prevention of malaria in travellers from the United Kingdom. PHLS Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine. Commun Dis Rep CDR Rev 7:R137–152PubMedGoogle Scholar
  20. 20.
    Hoerauf A, Nissen-Pähle K, Schmetz C, Henkle-Dührsen K, Blaxter ML, Büttner DW, Gallin MY, Al-Qaoud KM, Lucius R, Fleischer B (1999) Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility. J Clin Invest 103:11–18PubMedGoogle Scholar
  21. 21.
    Dreyer G, Ottesen EA, Galdino E, Andrade L, Rocha A, Medeiros Z, Moura I, Casimiro I, Beliz F, Coutinho A (1992) Renal abnormalities in microfilaremic patients with Bancroftian filariasis. Am J Trop Med Hyg 46:745–751PubMedGoogle Scholar
  22. 22.
    Taylor MJ, Cross HF, Bilo K (2000) Inflammatory responses induced by the filarial nematode Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic Wolbachia bacteria. J Exp Med 191:1429–1436PubMedGoogle Scholar
  23. 23.
    St. André A, Blackwell NM, Hall LR, Hoerauf A, Brattig N, Taylor M, Ford L., Hise A, Volkmann L, Lass JH, Diaconu E, Pearlman E (2002) A critical role for endosymbiotic Wolbachia bacteria and TLR4 signaling in the pathogenesis of river blindness. Science 295:1892–1895PubMedGoogle Scholar
  24. 24.
    Cross HF, Haarbrink M, Egerton G, Yazdanbakhsh M, Taylor MJ (2001) Severe reactions to filarial chemotherapy are associated with the release of Wolbachia endosymbionts into the blood. Lancet 358:1873–1875PubMedGoogle Scholar
  25. 25.
    Keiser PB, Reynolds SM, Awadzi K, Ottesen EA, Taylor MJ, Nutman TB (2002) Bacterial endosymbionts of Onchocerca volvulus in the pathogenesis of posttreatment reactions. J Infect Dis 185:805–811PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Achim Hoerauf
    • 1
    Email author
  • Sabine Mand
    • 1
  • Kerstin Fischer
    • 1
  • Thomas Kruppa
    • 2
  • Yeboah Marfo-Debrekyei
    • 2
  • Alexander Yaw Debrah
    • 2
  • Kenneth M. Pfarr
    • 1
  • Ohene Adjei
    • 3
  • Dietrich W. Büttner
    • 1
  1. 1.Department of HelminthologyBernhard Nocht Institute for Tropical MedicineHamburgGermany
  2. 2.Kumasi Centre of Collaborative ResearchKumasiGhana
  3. 3.School of Medical SciencesKwame Nkrumah University of Science and TechnologyKumasiGhana

Personalised recommendations