ABSTRACT
The increase in human babesiosis is of major concern to health authorities. In the USA, most of these cases are due to infections with Babesia microti, whereas in Europe B. divergens is the major cause of clinical disease in humans. Here we review the immunological and biological literature of glycosylphosphatidylinositol (GPI)-anchored merozoite proteins of human Babesia parasites with emphasis on their role in immunity, and provide some new bioinformatical information on B. microti GPI-Anchored Proteins (GPI-AP). Cattle can be vaccinated with soluble parasite antigens (SPA) of Babesia divergens that are released by the parasite during proliferation. The major component in SPA preparations appeared to be a 37â¯kDa merozoite surface protein that is anchored in the merozoite membrane by a GPI anchor. Animals could be protected by vaccination with the recombinant 37â¯kDa protein expressed in Escherichia coli, provided the protein had a hydrophobic terminal sequence. Based on this knowledge, a recombinant vaccine was developed against Babesia canis infection in dogs, successfully. In order to identify similar GPI-AP in B. microti, the genome was analysed. Here it is shown that B. microti encodes all proteins necessary for GPI assembly and its subsequent protein transfer. In addition, in total 21 genes encoding for GPI-AP were detected, some of which reacted particularly strongly with sera from B. microti-infected human patients. Reactivity of antibodies with GPI-anchored merozoite proteins appears to be dependent on the structural conformation of the molecule. It is suggested that the three-dimensional structure of the protein that is anchored in the membrane is different from that of the protein that has been shed from the merozoite surface. The significance of this protein's dynamics in parasite biology and immune evasion is discussed. Finally, we discuss developments in tick and Babesia vaccine research, and the role such vaccines could play in the control of human babesiosis.
Subject(s)
Antigens, Protozoan/immunology , Babesia microti/immunology , Babesiosis/prevention & control , Protozoan Vaccines/administration & dosage , Protozoan Vaccines/immunology , Animals , Disease Models, Animal , Dogs , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunologyABSTRACT
La babesiosis es una enfermedad zoonótica poco común, que en la mayoría de los casos es asintomática pero que en personas con alguna inmunodeficiencia puede llegar a ser fatal. La provocan diferentes tipos de babesia, las más frecuentes B. microti en Estados Unidos y B. divergens en Europa y es transmitida por la picadura de la garrapata de ciervo infectada, la lxodes scapularis. El mayor número de casos de la enfermedad se presenta principalmente en verano y primavera, en zonas de la costa noreste de Estados Unidos, Massachussets, especialmente en Nanmcket Island y en Long Island, Nueva York. También hay informes de casos observados en Wisconsin, California, Georgia, Missouri y algunos países europeos. La enfermedad puede causar fiebre, escalofrío, malestar general, fatiga, anemia hemolítica y puede durar desde días hasta meses. El diagnóstico se realiza por examen directo donde se observa al protozoario dentro de los glóbulos rojos. También hay pruebas de inmunofluorescencia y amplificación de ácidos nucleicos por reacción en cadena de la polimerasa PCR. El tratamiento que se ha venido utilizando es Quinina y Clindamicina, aunque tienen muchos efectos secundarios. Se han utilizado también otros medicamentos como azitromicina, tetraciclinas y atovaquona. La principal medida de prevención tiene que ver con el control del vector transmisor de la enfermedad.