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Macrofilaricidal Activity and Amelioration of Lymphatic Pathology in Bancroftian Filariasis after 3 Weeks of Doxycycline Followed by Single-Dose Diethylcarbamazine

In a placebo controlled trial, the effects of 21- and 10-day doxycycline treatments (200 mg/day) followed by single dose diethylcarbamazine (administered 4 months post treatment) on depletion of Wolbachia endobacteria from Wuchereria bancrofti, filaricidal activity, and amerlioration of scrotal lymph vessel dilation were studied in 57 men from Orissa, India. The 21-day doxycycline course reduced Wolbachia in W. bancrofti by 94% before diethylcarbamazine administration. After 12 months, all patients with this treatment were amicrofilaremic and different from the 10-day doxycycline (42.9%) and placebo (37.5%) groups, and significantly fewer were positive for scrotal worm nests (6.7%) compared with 10-day doxycycline (60%) and placebo (66.7%). Average scrotal lymph vessel diameters were reduced from 0.7 cm pre-treatment to 0.02 cm in patients after 21 days of treatment, while no significant changes were seen in the other groups. This latter feature confirms the beneficial effects of doxycycline on lymphatic dilation and thus adds to the existing evidence that doxycycline, in addition to being macrofilaricidal, may be used to prevent or reverse lymphatic pathology.

Received March 23, 2009. Accepted for publication July 13, 2009.

Acknowledgments: The authors thank the study participants for their cooperation, and Dr. Sidhard Padhi, Bhubaneswar, for assistance with patient care in the villages.

Financial support: We are grateful for financial support from the German Federal Ministry for Education and Research (BMBF), Berlin (Grant IND 02/010), and the Indian Council of Medical Research (ICMR). A.Y.D. was a recipient of scholarship from the German Academic Exchange Service (DAAD) for his PhD work.

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

Authors’ addresses: Sabine Mand, Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany, Tel: 49-228-287-15675, Fax: 49-228-287-19573, E-mail: mand{at}microbiology-bonn.de. Kenneth Pfarr, Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany, Tel: 49-228-287-15675, Fax: 49-228-287-19573, E-mail: pfarr{at}microbiology-bonn.de. Prakash K. Sahoo, Division of Immunology, Regional Medical Research Centre, Indian Council of Medical Research, Bhubaneswar 751023, India, Tel: 91-674-2301900 or 2302746, Fax: 91-674-2300728. Ashok K. Satapathy, Division of Immunology, Regional Medical Research Centre, Indian Council of Medical Research, Bhubaneswar 751023, India, Tel: 91-674-2301900 or 2302746, Fax: 91-674-2300728. Sabine Specht, Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany, Tel: 49-228-287-15675, Fax: 49-228-287-19573, E-mail: specht{at}microbiology-bonn.de. Ute Klarmann, Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany, Tel: 49-228-287-15675, Fax: 49-228-287-19573, E-mail: klarmann{at}yahoo.de. Alexander Y. Debrah, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR) and Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana, Tel: 233-51-60351, Fax: 233-51-62017, E-mail: yadebrah{at}yahoo.com. Balachandran Ravindran, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023, India, Tel: 91-674-2301900 or 2302746, Fax: 91-674-2300728, E-mail: ravindran8{at}gmail.com. Achim Hoerauf, Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany, Tel: 49-228-287-15675, Fax: 49-228-287-19573, E-mail: hoerauf{at}microbiology-bonn.de.