Current trends in research on tissue stage of malaria.

The tissue stage or the exoerythrocytic (EE) stage of the malaria parasite, for many years remained the most neglected form mainly because of its inaccessibility being located in the liver. The advent of in vitro techniques resulting in the successful cultivation of these forms in primary hepatocyte cultures and a variety of cell lines has greatly augmented research on these stages and have provided unique in vitro systems which can be used as primary screens for candidate chemotherapeutic and immunoprophylactic agents and have facilitated better understanding of the sporozoite-hepatocyte interactions. Sensitive and specific nucleic acid probes (DNA and ribosomal RNA) have been developed to quantify EE stages in infected livers. Efforts to establish SCID mouse as a model for cultivation of EE stages of human malaria parasites have been encouraging. The earlier assumptions that these tissue stages are free from immune attack have been proven wrong and the hepatic phase itself now appears to be essential for the induction of protection against the pre-erythrocytic stages. Liver stage specific antigens have been identified in recent years. Despite its intracellular position, this 'hidden' form has been found to constitute a target for antibodies, cytokines, and cytotoxic T cells. The present review focuses on the advances in research on the 'silent' stage of malaria parasites.