The role of Doxycycline in the Amelioration of Filarial Hydrocele

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There is an urgent need for a macrofilaricidal drug that can improve or halt progression of hydrocele pathology in lymphatic filariasis. In addition, new drugs with modes of action different to ivermectin must urgently be developed to serve as backup should ivermectin resistance develop. While diethylcarbamazine has partial macrofilaricidal effects, it does not ameliorate filarial hydrocele and cannot be used in Africa because of co-endemicity with onchocerciasis. The purpose of this study was to determine whether a six-week course of 200mg doxycycline could ameliorate filarial hydrocele and its associated clinical conditions. A randomized, double-blinded, placebo-controlled, clinical trial was conducted with 44 hydrocele patients. Twenty one (21) were treated with 200 mg of doxycycline for 6 weeks whilst 23 received placebo treatment for 6 weeks. Ninety one percent (91%) of the patients completed the full course of treatment. All study participants were given 150 µg/kg ivermectin plus 400mg albendazole 6 months after treatment in accordance with the nationwide mass drug administration programme. Ultrasound examinations of the scrotum were carried out for all patients at pre-treatment and at the 12-months and 24-month follow-ups. Patients were examined for dilation in scrotal lymphatic vessels, hydrocele stage, thickness of the scrotal skin and filaria dance signs. Parasitological examinations for circulating filaria antigens and microfilarial loads were also carried out. At the 12-month follow-up, there were no significant variations in the measured parameters between the doxycycline and placebo-treated patients. After 24 months of treatment, 94% of the doxycycline-treated patients had significant improvement and halt in progression of the dilations in the scrotal lymphatic vessels compared to 46% of placebo-treated patients (p=0.318). Eighty two (82%) of doxycycline-treated patients had a significant improvement and halt in progression of hydrocele stage compared to 46% of placebo-treated patients (p=0.0349). The improvement was observed only in patients with early stage hydrocele. All the 6 worm nests in the doxycycline-treated patients had been lost after 24 months whilst thickening in the scrotal skin of 47% of doxycycline-treated patients were significantly improved as against 33% in placebo-treated patients (p=0.0120). Circulating filaria antigen levels did not vary significantly between the two groups (p=0.5726). Treatment with doxycycline was well tolerated as the incidence of adverse events was not significantly different between the treatment groups (p=0.3148). The study demonstrated that, in addition to its macrofilaricidal activity, a six-week course of 200mg doxycycline has ameliorative effect on filarial hydrocele. This effect occurred even in patients who had no active infection. Therefore, doxycycline can be used in hydrocele patients in whom the current antifilarial drugs do not provide amelioration.
A Thesis submitted to the Department of Clinical Microbiology,Kwame Nkrumah University of Science and Technology in partial fulfillment of the requirements for the degree of Master of Philosophy, 2011