Doxycycline targeting of wolbachia endosymbiotic bacteria in the treatment of wuchereria bancrofti infections in the Western Region of Ghana

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Chemotherapeutic approaches to the control and treatment of filarial disease have normally been a difficult topic because radical curative agents are not available. Present control strategies rely on drugs (ivermectin and albendazole) thai have only microfilaricidal activities (Ismail, 2001). As such, there is the need for a macrofilaricide or long term sterilising agent to complement ivermectin. The effect of tetracycline on the symbiotic endobacteria Wolbachia, in filarial worms has led to a novel chemotherapeutic approach in Wuchereria hancrofti infection and disease. In the Nzema East district in the Western Region of Ghana, 135 microfilarial positive patients were recruited for a double blind and an open group study. 110 patients were recruited for the double blind study which consisted of four groups. Two groups received 200mg/day doxycycline for either 3 weeks or 6 weeks. The other two groups were given placebo for 3 weeks and 6weeks. The open group study was undertaken with 25 patients. Eighteen patients were treated for 4 weeks with doxycycline and the rest served as controls without treatment. The effect of the doxycycline on Woihachia depletion was assessed at four months after treatment. All the doxycycline and placebo/control treated patients were given ivermectin (150mg/kg) and albendazole (400mg) four months after treatment and re-examined at 12 and 24 months after treatment. Parameters examined included pre-treatment microfilarial analysis, post-treatment microfilarial loads at 4, 12 and 24 months after doxycycline treatment, adverse reactions due to doxycycline (during doxycycline treatment) and also adverse effect due to ivermectin and albendazole (48 hours after ivermectin and albenda.zole treatment). Doxycycline was well tolerated with few incidents of adverse effects (18.1%) in contrast to the placebo groups (23.8%). Microfilarial assessment at 4 months did not yield significant results in both the 3 weeks and the 6 weeks regimen when compared with their placebo counterparts. Significant difference in the rnicrofilarial loads was observed in the four weeks group when compared with its control (p 0.0144). 12 months after treatment significant difference was observed in all the treatment groups when compared with their controls (3weeks p = 0.0004, 4weeks p = <0.0001 and 6weeks p = <0.0001). The significant difference was sustained up to 24 months after treatment in all (he treatment groups. The qualitative PCR revealed a total depletion of Wolbachia at 2 months in the 4 weeks and the 6weeks groups. For the 3 weeks treatment group, two patients remained positive even at 12 months after treatment, However 31 out of a total of 46 placebo patients examined at 12 months were positive. 4weeks and 6weeks treatment with doxycycline has proved effective in the depletion of Wolbachia in Wuchereria hancrofti infection thereby exhibiting a long term sterilizing effect. Though 3 weeks treatment could also deplete Woihachia, the depletion was not as complete as the 4 and 6 weeks regimen. The combination of doxycycline with ivermectin /albendazole reduced the microfliarial loads and the Wolbachia depletion sustained the amicrofilaraemia of the various treatment groups up to 24 months after treatment. Since 3 weeks doxycycline treatment was effective in causing sterility in the Wuchereria bancrofti but not as effective as the 4 and 6 weeks, combination of 4 weeks doxycycline with a single dose of ivermectin/albendazole will be enough to treat selected populations of bancroftian filariasis infection. A longer duration to achieve macrofilaricidal activity is worth considering. In addition vector control should also be incorporated especially in endemic areas.
A thesis submitted to the Department of Clinial Microbiology, School of Medical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, for the award of the degree of M. PHIL. Clinical Microbiology, 2005