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Paratransgenic Control of Leishmaniasis: New Developments

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Pathogenesis of Leishmaniasis

Abstract

Leishmaniasis is a devastating neglected tropical disease caused by approximately 20 different species of Leishmania parasites. These obligate intercellular protozoa are spread naturally to humans by female phlebotomine sand flies of the genus Phlebotomus (Old World) or Lutzomyia (New World). Depending on the infecting parasite and the innate host-immune response, the clinical manifestation of leishmaniasis ranges from cutaneous ulcerations to system infections. It is therefore not surprising that treatment of leishmaniasis varies greatly with the type of disease (cutaneous, mucosal, or visceral). Currently, no vaccines are available for any form of leishmaniasis, and control of disease has focused largely on vector eradication through pesticide use. The Visceral Leishmaniasis (VL) Elimination Initiative was launched in the 2005 between the governments of India, Nepal and Bangladesh and the WHO. The aim of this initiative is to reduce annual VL incidence in this region to below 1/10,000 inhabitance by 2015. Despite some early success, recent reports are now citing difficulties in sustaining prolonged spraying campaigns and emerging public concerns regarding insecticide use and environmental toxicity. Further, new populations of sand flies in these endemic regions in India have now gained resistance to DDT. For these reasons, alternative and integrative vector control strategies are needed to reach the VL elimination target date in 2015.

The paratransgenic strategy was initially developed to control the vectorial transmission of Trypanosoma cruzi, the protozoan parasite responsible for Chagas disease, by blood-sucking triatomine bugs. In this strategy, bacterial flora native to disease-transmitting vectors are isolated and genetically transformed in vitro to export molecules that interfere with pathogen transmission. The genetically altered symbionts are then re-introduced into the host vector where expression of engineered molecules affects the host’s ability to transmit the pathogen. In this review, we will discuss the strategy that we have adopted to adapt the paratransgenic approach to control vectorial transmission of leishmania in sand flies, and describe how two effector molecules, antimicrobial peptides (AMP’s) and single chain antibodies (scFv’s), can be utilized to specifically target the parasites in sand fly. Further, we address the evolving concepts related to field dispersal of engineered bacteria as part of the paratransgenic control strategy coupled with the attendant risk assessment evaluation that is critical for field release. We conclude with the development and testing of a “barrier” method of containment and dispersal for paratransgenic technologies.

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Authors and Affiliations

  1. Department of Internal Medicine, Center for Global Health, University of New Mexico and New Mexico VA Health Care System, MSC10 5550, Albuquerque, NM, 87131, USA

    Ivy Hurwitz, Adam Forshaw, Kari Yacisin & Ravi Durvasula

  2. Department of Entomology, Kansas State University, Manhattan, KS, USA

    Marcelo Ramalho-Ortigao

  3. Department of Pathology, The Ohio State University, Columbus, OH, USA

    Abhay Satoskar

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  1. Ivy Hurwitz
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  2. Adam Forshaw
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  3. Kari Yacisin
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  4. Marcelo Ramalho-Ortigao
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  5. Abhay Satoskar
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  6. Ravi Durvasula
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Correspondence to Ivy Hurwitz .

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Editors and Affiliations

  1. Department of Pathology, The Ohio State University, Columbus, Ohio, USA

    Abhay Satoskar

  2. Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA

    Ravi Durvasula

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Hurwitz, I., Forshaw, A., Yacisin, K., Ramalho-Ortigao, M., Satoskar, A., Durvasula, R. (2014). Paratransgenic Control of Leishmaniasis: New Developments. In: Satoskar, A., Durvasula, R. (eds) Pathogenesis of Leishmaniasis. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9108-8_3

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