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

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Abstract

The discovery of the endosymbiont Wolbachia, which has a mutualistic relationship with filarial nematodes, and its importance in filarial parasite biology has provided a lead for developing novel chemotherapeutic agents against human filariasis. Wolbachia also appears to be involved in immunopathological responses as well as adverse reactions after antifilarial therapy. The aim of the present study was to explore the potential of administering anti-Wolbachial therapy before antifilarial treatment to improve the filaricidal efficacy of the present-day filaricide diethylcarbamazine. An additional objective was to minimize host inflammatory reactions using a rodent model Mastomys coucha and Meriones unguiculatus infected with human lymphatic filariid Brugia malayi. We observed: (1) a 40-day treatment schedule of tetracycline alone resulted in delayed reduction in microfilaraemia and a low degree of macrofilaricidal efficacy; (2) tetracycline therapy followed by 100 mg/kg diethylcarbamazine (DEC) ×5 days led to marked reduction in microfilaraemia from day 48 onward after initiation of treatment. The combination treatment also brought about ∼70% death of adult B. malayi and sterilization of 82.3% of the surviving female worms, thus exhibiting remarkable enhancement in the antifilarial activity of DEC; (3) tissue inflammatory reactions and pathogenesis were significantly reduced as observed by histopathology, and peritoneal macrophage mediated oxidative burst shown by florescence-activated cell sorting (FACS) analysis using dichlorofluorescein diacetate (DCF-DA); and (4) the characteristic filarial antigen-specific and mitogen-specific cellular unresponsiveness was significantly reversed, possibly due to marked clearance of microfilaraemia. It is therefore advisable to give an anti-Wolbachial antibiotic trial before starting antifilarial therapy to achieve maximum benefits.

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Acknowledgements

We are thankful to Mr. A.K. Roy and R.N. Lal for their technical assistance in experimental maintenance of B. malayi infection. The financial assistance in the form of the senior research fellowships from the Council of Scientific and Industrial Research, New Delhi, to two co-authors (S.S and P.B.) is gratefully acknowledged.

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  1. Division of Parasitology, Central Drug Research Institute, Chattar Manzil Palace, Lucknow, 226001, Uttar Pradesh, India

    Shilpy Shakya, Preeti Bajpai & Shailja Misra-Bhattacharya

  2. Division of Toxicology, Central Drug Research Institute, Chattar Manzil Palace, Lucknow, 226001, Uttar Pradesh, India

    Sharad Sharma

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  1. Shilpy Shakya
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  2. Preeti Bajpai
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  4. Shailja Misra-Bhattacharya
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Correspondence to Shailja Misra-Bhattacharya.

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Shakya, S., Bajpai, P., Sharma, S. et al. Prior killing of intracellular bacteria Wolbachia reduces inflammatory reactions and improves antifilarial efficacy of diethylcarbamazine in rodent model of Brugia malayi . Parasitol Res 102, 963–972 (2008). https://doi.org/10.1007/s00436-007-0861-8

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