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Reduction in Levels of Plasma Vascular Endothelial Growth Factor-A and Improvement in Hydrocele Patients by Targeting Endosymbiotic Wolbachia sp. in Wuchereria bancrofti with Doxycycline

Alexander Y. Debrah, Sabine Mand, Yeboah Marfo-Debrekyei, Linda Batsa, Kenneth Pfarr, Bernard Lawson, Mark Taylor, Ohene Adjei, AND Achim Hoerauf^*

The treatment for hydrocele is expensive, invasive surgery—hydrocelectomy. A drug that could prevent or improve this condition could replace or supplement hydrocelectomy. In Ghana, 42 hydrocele patients participated in a double-blind, placebo-controlled trial of a six-week regimen of doxycycline, 200 mg/day. Four months after doxycycline treatment, patients received 150 µg/kg of ivermectin and 400 mg of albendazole, which is used for mass chemotherapy in this area. Patients were monitored for levels of Wolbachia sp., microfilaremia, antigenemia, plasma levels of vascular endothelial growth factor-A (VEGF-A) and stage/size of the hydrocele. Wolbachia sp. loads/microfilaria, microfilaremia, and antigenemia were significantly reduced in the doxycycline-treated patients compared with the placebo group. The mean plasma levels of VEGF-A were decreased significantly in the doxycycline-treated patients who had active infection. This finding preceded the reduction of the stage of hydrocele. A six-week regimen of doxycycline treatment against filariasis showed amelioration of pathologic conditions of hydrocele patients with active infection.

Received December 4, 2007. Accepted for publication February 26, 2009.

Acknowledgments: We thank the District Health Management team at Axim (Nzema East District), Western Region, Ghana for cooperation, and Pfizer Inc. (Karlsruhe, Germany) for generously provided vibramycin and placebo tablets.

Financial support: This study was supported by the European Commission(EU-grantICA4-CT-2002-10051) and the VW-Foundation (grant 1/81306). Alexander Y. Debrah is a recipient of a scholarship from the German Academic Exchange Service for his PhD work.

^* Address correspondence to Achim Hoerauf, Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse, 25, D-53105 Bonn, Germany. E-mail: hoerauf{at}microbiology-bonn.de

These authors contributed equally to this paper.

Authors’ addresses: Alexander Y. Debrah, Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse, 25, D-53105 Bonn, Germany, Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, and Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana. Sabine Mand, Kenneth Pfarr, and Achim Hoerauf, Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse, 25, D-53105 Bonn, Germany. Yeboah Marfo-Debrekyei and Linda Batsa, Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana. Bernard Lawson, Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Mark Taylor, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom. Ohene Adjei, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

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				S. Mand, K. Pfarr, P. K. Sahoo, A. K. Satapathy, S. Specht, U. Klarmann, A. Y. Debrah, B. Ravindran, and A. Hoerauf Macrofilaricidal Activity and Amelioration of Lymphatic Pathology in Bancroftian Filariasis after 3 Weeks of Doxycycline Followed by Single-Dose Diethylcarbamazine Am J Trop Med Hyg, October 1, 2009; 81(4): 702 - 711. [Abstract] [Full Text] [PDF]