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Strain Specificity in the Liver-Stage Development of Plasmodium Falciparum in Primary Cultures of new World Monkey Hepatocytes

Pascal MilletMalaria Branch, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, US Department of Health and Human Services, Department of Pathology, Case Western Reserve University, Biomedical Research Institute, Atlanta, Georgia

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Carter T. AtkinsonMalaria Branch, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, US Department of Health and Human Services, Department of Pathology, Case Western Reserve University, Biomedical Research Institute, Atlanta, Georgia

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Masamichi AikawaMalaria Branch, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, US Department of Health and Human Services, Department of Pathology, Case Western Reserve University, Biomedical Research Institute, Atlanta, Georgia

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Michael R. HollingdaleMalaria Branch, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, US Department of Health and Human Services, Department of Pathology, Case Western Reserve University, Biomedical Research Institute, Atlanta, Georgia

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William E. CollinsMalaria Branch, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, US Department of Health and Human Services, Department of Pathology, Case Western Reserve University, Biomedical Research Institute, Atlanta, Georgia

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Primary cultures of Aotus and Saimiri monkey hepatocytes were infected with sporozoites of the Plasmodium falciparum NF 54 strain from mosquitoes fed on gametocyte cultures, and with sporozoites of the P. falciparum Santa Lucia strain from mosquitoes fed on an infected Aotus monkey. After 4–8 days, one exoerythrocytic (EE) parasite per 30,000 sporozoites was detected in one of three experiments performed with the P. falciparum NF54 strain. However, numerous EE parasites were detected in Aotus and Saimiri cells infected with sporozoites of the P. falciparum Santa Lucia strain. At day 6, most of the parasites contained several hundred nuclei, and were morphologically similar to those previously described in vivo using light or electron microscopy. A monoclonal antibody directed against the repeat region of the circumsporozoite protein of P. falciparum labeled the plasma and parasitophorous vacuole membrane of five-day-old EE parasites by immunoelectron microscopy, thus supporting previous observations by immunofluorescence indicating that the CS protein persists throughout the EE development of P. falciparum. These results demonstrate that liver stages of P. falciparum can be obtained in Aotus and Saimiri monkey cells; they also suggest a parasite strain specificity for hepatocytes.

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