Use of liposomized tetracycline in elimination ofWolbachiaendobacterium of human lymphatic filariidBrugia malayiin a rodent model

Abstract

Wolbachia bacteria, being filarial parasite symbiont have been implicated in a variety of roles, including development, fecundity and the pathogenesis of the filarial infections. Among various strategies used in the treatment of experimental filariasis, the elimination of symbiont Wolbachia seem to offer an efficient means of curing the disease. The antiwolbachial property of tetracycline has been well worked out; however, treatment needs to be continued for a prolonged period of time to achieve complete elimination of Wolbachia from the filarial parasites and their subsequent killing. This results in acute toxicity, thus limiting its practical utility for clinical implementation. In order to increase efficacy of the antibiotic with minimal toxic manifestations, we developed liposomized formulation of the tetracycline. The liposomized tetracycline was found to be significantly more effective when compared to the free form of the drug. In contrast to the 90/120 days oral administration of the drug, the treatment schedule using the liposomized form of the drug was reduced to 12 alternate days with better efficacy of the treatment.

In vitro and in vivo antifilarial potential of marine sponge, Haliclona exigua (Kirkpatrick), against human lymphatic filarial parasite Brugia malayi

“…The antifilarial activity of the crude extract of H. exigua and its fraction in vivo was validated in M. coucha infected with L3 stage of B. malayi. M. coucha infected with subperiodic B. malayi are being used worldwide as an excellent experimental rodent model for evaluating the antifilarial activity of synthetic and natural products (Sänger et al 1981;Zahner et al 1988Zahner et al , 2001aSchares et al 1994;Owais et al 2003;Bajpai et al 2005aBajpai et al , b, 2007Shakya et al 2008). Antifilarial activity (macrofilaricidal and microfilaricidal) of the crude extract and its chloroform fraction was observed on experimental animals at the doses used.…”

Prior killing of intracellular bacteria Wolbachia reduces inflammatory reactions and improves antifilarial efficacy of diethylcarbamazine in rodent model of Brugia malayi

“…A real-time PCR/ immuno-histochemistry analysis would have shown the quantitative depletion of Wolbachia; however, several earlier reports have discussed this, including studies carried out in the brugian model (Simoncini et al 2001;Casiraghi et al 2002;Hoerauf et al 2003a, b). Our earlier publication dealing with PCR using B. malayi Wolbachia primers (Bsymbf and Bsymbr) revealed the absence of PCR product after 90 or 120 continuous days of tetracycline treatment, in contrast to that of untreated worm (Bajpai et al 2005). The graph of microfilaraemia after tetracycline treatment alone for 40 consecutive days shows slight reduction in microfilaraemia as compared to low and sustained increase in microfilaria (mf) density in untreated control animals, illustrating the effect of antibiotic on embryogenesis of female worms.…”

“…Tetracycline/doxycycline treatment for 30-60 consecutive days covering the period of sexual development of worms in the host is reported to partially remove Wolbachia by causing sterilization of female worms but not their death Bandi et al 1999). Prolonged treatment for 90-120 days is required to completely eliminate Wolbachia and demonstrate high adulticidal efficacy (Casiraghi et al 2002;Chirgwin et al 2003a, b;Bajpai et al 2005). Our earlier publication dealing with polymerase chain reaction (PCR) with these primers had revealed absence of PCR product after 90 or 120 continuous days of tetracycline treatment (Bajpai et al 2005).…”

“…Prolonged treatment for 90-120 days is required to completely eliminate Wolbachia and demonstrate high adulticidal efficacy (Casiraghi et al 2002;Chirgwin et al 2003a, b;Bajpai et al 2005). Our earlier publication dealing with polymerase chain reaction (PCR) with these primers had revealed absence of PCR product after 90 or 120 continuous days of tetracycline treatment (Bajpai et al 2005). Tetracycline has been shown to be effective in various experimental models against the developing stages of filarial parasites; in the majority of the studies, the treatment was initiated with the initiation of L 3 infection (Bosshardt et al 1993;Hoerauf et al 1999;Chirgwin et al 2003a, b;Rajan 2004).…”

Wolbachia in filarial parasites: Targets for filarial infection and disease control

“…One study has investigated the use of a liposomized form of tetracycline to treat B. malayi infection in the rodent Mastomys coucha [33]. In this investigation, tetracycline entrapped within liposomes was given subcutaneously to infected rodents, and both microfilarial counts and macrofilaricidal activity were compared with those animals treated with free tetracycline via subcutaneous injection and those treated with free tetracycline orally.…”