Significance of Circumsporozoite-Specific Antibody in the Natural Transmission of Plasmodium Falciparum, Plasmodium Vivax, and Plasmodium Malariae in an Aboriginal (Orang Asli) Population of Central Peninsular Malaysia

Daniel M. GordonUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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Donald R. DavisUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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Melinda LeeUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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Chris LambrosUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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Bruce A. HarrisonUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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Reena SamuelUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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Gary H. CampbellUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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M. JegathesanUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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K. SelvarajanUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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George E. Lewis JrUS Army Medical Research Unit, Institute for Medical Research, Department of Immunology, Walter Reed Army Institute of Research, Division of Parasitic Diseases, Malaria Branch, Center for Infectious Diseases, Centers for Disease Control, Gombak Hospital, Department of Orang Asli Affairs, Kuala Lumpur, Malaysia

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Two hundred and seventy-five Orang Asli volunteers living in nine villages in the Pos Legap Valley of Perak State, penisular Malaysia, participated in a prospective study designed to characterize the epidemiological, parasitological, and entomological characteristics of Plasmodium falciparum, P. vivax and P. malariae malaria transmission. Prevalence rates for the three plasmodial species at initiation of the study ranged from 56% in the 0-4-year-old age group to 0% in individuals over the age of 40. Entomological surveys were conducted, enabling us to determine mosquito salivary gland-positive rates and entomological inoculation rates of 1.2 infectious mosquito bites per person per month for P. falciparum, 2.4 for P. vivax, and 0.3 for P. malariae. Cumulative incidence rates over the 16 weeks of the study, following radical cure of all volunteers, were 22.5% for P. falciparum, 12.7% for P. vivax, and 1.5% for P. malariae. The median baseline antibody titer against the immunodominant repetitive B cell epitope of P. falciparum or P. vivax circumsporozoite protein was significantly higher for volunteers who did not become parasitemic. Volunteers were selected for further study if they had evidence of being challenged with P. falciparum sporozoites during the study, based on a two-fold or greater increase in antibody titer against the immunodominant repetitive B cell epitope of the circumsporozoite protein. Resistance to infection was seen in six of 10 individuals who had high (> 25 OD units) baseline ELISA titers, compared with only three of 24 individuals who had low baseline ELISA titers (x2 P < 0.02). A similar analysis for P. vivax did not show a significant correlation.

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