The development and routine application of high-density exoerythrocytic-stage cultures of Plasmodium berghei

Methods are reviewed for the culture of the exoerythrocytic stages of Plasmodium berghei wherein development reproducibly reflects growth observed in vivo in laboratory rodents. The combination of these methods with the culture of both asexual and sexual blood stages has allowed the completion of the entire vertebrate phase of malaria development in vitro. The development of new methods for high-density exoerythrocytic-stage culture combined with robust statistical analysis of parasite growth by morphological (light microscopy), or DNA probe methods now allows the critical and precise evaluation of chemotherapeutic or immunological treatments. These methods are illustrated by data obtained on pyrimethamine, primaquine and a hydroxynaphthoquinone. Some of the new avenues of research made feasible by the high-density cultures, e.g., direct immunization to produce monoclonal antibodies and biochemical studies are discussed.