Towards a Preventive Strategy for Toxoplasmosis: Current Trends, Challenges, and Future Perspectives for Vaccine Develop

With its facultative ability to induce various types of infection in its hosts, Toxoplasma gondii remains a fascinating and enigmatic pathogen. As a parasite, despite its primitive unicellular structure, it possesses a highly sophisticated arsenal of inva

  • PDF / 292,552 Bytes
  • 12 Pages / 504.57 x 720 pts Page_size
  • 107 Downloads / 154 Views

DOWNLOAD

REPORT


1

Introduction Toxoplasmosis, caused by the unicellular intracellular protozoan parasite Toxoplasma gondii, is a cosmopolitan disease infecting almost all endothermic animals, including humans. Human infections with T. gondii are primarily symptomless and induce a self-limiting disease in immunocompetent individuals. However, in immunocompromised individuals the effects of infection are much more severe. Furthermore, vertical transmission during pregnancy can induce miscarriage, cerebral lesions, and ocular complications [1]. Toxoplasmosis in animals, mainly sheep and goats, has great economic impact as it causes abortions, stillbirths, and neonatal fatalities. Additionally, the consumption of raw or semi-cooked meat contaminated with tissue cysts of T. gondii is considered the main route of parasite transmission to humans [2]. During infection, the parasite disseminates throughout the body and converts from tachyzoites to bradyzoites (tissue cysts forms), which are kept under control, but not entirely eliminated by the host’s cellular immune responses; hence, medical intervention is required [3]. T. gondii has a complex life cycle, making development of a potent vaccine to reduce the hazards of toxoplasmosis far from straightforward. As a heteroxenous pathogen, T. gondii requires multiple hosts to complete its life cycle. The life cycle includes a sexual stage in the definitive host (wild or domestic felines) characterized by sporozoites in sporulated oocysts, and asexual stages represented by tachyzoites (the rapidly proliferative forms) and bradyzoites (the dormant forms), both of which occur in the definitive and intermediate hosts [4, 5]. Establishment of novel control and prevention strategies for toxoplasmosis is essential for protecting

Sunil Thomas (ed.), Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases, Methods in Molecular Biology, vol. 1404, DOI 10.1007/978-1-4939-3389-1_10, © Springer Science+Business Media New York 2016

153

154

Ragab M. Fereig and Yoshifumi Nishikawa

public health and livestock production. Currently, only one commercial vaccine (Toxovax®, Intervet), based on live attenuated tachyzoites of the T. gondii S48 strain, is available for veterinary use in a limited number of countries, where it is used primarily for minimizing the incidence of abortion in sheep [6]. This vaccine has certain disadvantages and cannot be used for humans as because live vaccines possess the capacity to restore parasite virulence and provoke iatrogenic infection [7]. Moreover, most available drugs used for treatment and control of toxoplasmosis have several limitations; hence, discovery of highly effective and safe chemotherapies remains an essential goal. Whereas some of the drugs in use for toxoplasmosis are only partially effective in treating acute infections, their efficacy is abrogated for treatment of chronic infections, and most have high toxicity [8]. Also, there are currently no effective treatments that can prevent the severe neurological, ocular, cardiac and cer