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FATAL MALARIA INFECTION IN TRAVELERS: NOVEL IMMUNOHISTOCHEMICAL ASSAYS FOR THE DETECTION OF PLASMODIUM FALCIPARUM IN TISSUES AND IMPLICATIONS FOR PATHOGENESIS

Plasmodium falciparum is a significant cause of morbidity and mortality in travelers to areas where the parasite is endemic. Non-specific clinical manifestations may result in failure to recognize malaria until autopsy, when it is often too late to obtain whole blood for microscopic evaluation. The use of immunohistochemical (IHC) assays in the detection of three P. falciparum antigens, histidine rich protein-2 (HRP-2), aldolase, and Plasmodium lactate dehydrogenase (pLDH), was evaluated in formalin-fixed paraffin-embedded autopsy tissues from five travelers to malaria-endemic areas, whose deaths were initially suspected to have been caused by other bacterial or viral hemorrhagic fevers. The HRP-2 assay was specific for P. falciparum, whereas the aldolase and pLDH assays also reacted with P. vivax. Immunostaining patterns were predominately cytoplasmic and membranous. P. falciparum antigens were detected in a variety of organs but were most abundant in the blood vessels of brain, heart, and lung tissues.

Received July 31, 2006. Accepted for publication August 16, 2006.

Acknowledgments: We thank Dr. Makler, Flow Inc., and Dr. Norm Moore, Binax Inc., for kindly donating samples of antibodies for use in this study. We also thank Mitesh Patel for assistance with receiving and in-processing all tissue specimens.

Financial support: This research was supported in part by an Emerging Infectious Diseases Fellowship from the Association of Public Health Laboratories and by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention, National Center for Infectious Diseases, Infectious Disease Pathology Activity, by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the CDC. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agencies.

^* Address correspondence to Sherif R. Zaki, CDC/IDPA, 1600 Clifton Road, MSG-32, Atlanta, GA 30333. E-mail: sxz1{at}cdc.gov

Authors’ addresses: Gillian L. Genrich, Jeannette Guarner, Christopher Paddock, Wun-Ju Shieh, Patricia Greer, and Sherif R. Zaki, CDC/NCID/IDPA, 1600 Clifton Rd., MS-G32, Atlanta, GA 30329-4018, Telephone: 404-639-3889, Fax: 404-639-3043. John W. Barnwell, CDC/NCID/Malaria Branch, 4770 Buford Hwy., MS-F36, Bldg 109, Chamblee, GA 30341-3717, Telephone: 770-488-4528, Fax: 770-488-4253.

Reprint requests: Sherif R. Zaki, CDC/NCID/IDPA, 1600 Clifton Rd., MS-G32, Atlanta, GA 30329-4018.

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