Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline.

Alexander Yaw Debrah,Anna Albers,Yeboah Marfo-Debrekyei,Kenneth Pfarr,Ute Klarmann,Achim Hoerauf,Sabine Specht,Linda Batsa,Ohene Adjei,Sabine Mand

doi:10.1155/2011/201617

Abstract

Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF), it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200 mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10 mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS). Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti.

Highlights

120 million people in Africa, Asia, and America are infected with the filarial nematodes Wuchereria bancrofti or Brugia malayi, resulting in lymphatic filariasis (LF), of which more than 40 million suffer from the debilitating lymphatic pathologies such as lymphedema, elephantiasis, and hydrocele
One promising area is the use of antibiotics to deplete the Wolbachia endosymbionts found in most filarial species, which leads to the inhibition of worm development, embryogenesis, Journal of Parasitology Research fertility, and viability in human onchocerciasis [11,12,13,14] and LF [15,16,17,18]
We have recently demonstrated that a fourweek course of doxycycline, followed by a single dose of ivermectin treatment in bancroftian filariasis, is effective at reducing Wolbachia levels by 95% and, more importantly, it leads to strong macrofilaricidal activity with improvement of pathology [16, 17]

Summary

Introduction

120 million people in Africa, Asia, and America are infected with the filarial nematodes Wuchereria bancrofti or Brugia malayi, resulting in lymphatic filariasis (LF), of which more than 40 million suffer from the debilitating lymphatic pathologies such as lymphedema, elephantiasis, and hydrocele. The classical drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) have been used for the last two decades as the major mode of intervention for filarial infection in successful mass drug administration (MDA) programmes [2,3,4] These drugs are mainly microfilaricidal [5,6,7,8,9,10], that is, killing the first larval stage, the microfilariae (Mf). DEC plus albendazole only partially kill adult worms that are the causes of pathology in LF (urogenital disorders and lymphedema), research is ongoing to discover novel antifilarial drugs with strong macrofilaricidal activity. A shorter regimen with antibiotics or more effective antifilarial drugs would be advantageous for the treatment of the large populations or for individual treatment, for example, in outpatient clinics, and for children

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Results

Conclusion