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Microscopy Underestimates the Frequency of Plasmodium Falciparum Infection in Symptomatic Individuals in a Low Transmission Highland Area

In an area with unstable malaria transmission, detection of Plasmodium falciparum infection in 379 symptomatic individuals was assessed by microscopy and three polymerase chain reaction (PCR) methodologies. P. falciparum infection was detected in 25% of patients by microscopy, 37% by nested PCR, 41% by merozoite surface protein-2 (MSP-2) PCR, and 45% by a ligase detection reaction-fluorescent microsphere assay (LDR-FMA). Of the 64 individuals who were LDR-FMA positive, microscopy negative and did not receive treatment, 8 (12.5%) had persistent symptoms and returned for treatment. Malaria attributable fraction (MAF) in symptomatic individuals was 14.6% by microscopy (95% confidence interval [CI] = 6.6–21.8%) and 28.2% by nested PCR (95% CI = 17.9–37.2%). In this highland area, P. falciparum infection in symptomatic individuals is detected more frequently by PCR than microscopy, and most frequently by LDR-FMA. P. falciparum infection appears to resolve without treatment in most LDR-FMA-positive, microscopy-negative individuals, but is persistent in a subset of these individuals and requires treatment.

Received December 13, 2007. Accepted for publication May 10, 2008.

Acknowledgments: We thank the study participants for their involvement in the study; the field assistants, microscopists, and clinical officers in both highland sites for their collection of data; Jackson Abuya and Livingstone Wanyama for their microscopy testing; and David Koech, the study site coordinator, and Samson Adoka, the field study supervisor, for their work on this study. We also thank Kim Lindblade for her supervision of the Malaria Early Warning Systems study. The field work for this study was performed while the PI (C. John) was a faculty member at Case Western Reserve University. This paper is published with the permission of the Director, KEMRI.

Financial support: This work was supported by grants from the National Institutes of Allergy and Infectious Diseases (AI056270 and an Opportunity Pool award).

^* Address correspondence to David M. Menge, University of Minnesota, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th St. SE, Minneapolis, MN 55455. E-mail: menge023{at}umn.edu

Authors’ addresses: David M. Menge and Chandy C. John, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN 55455. Kacey C. Ernst, University of Arizona College of Public Health, Tucson, AZ 85724. John M. Vulule, Climate and Human Health Research Unit, Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya. Peter A. Zimmerman, The Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106-7286. Hongfei Guo, Office of Clinical Research and Division of Biostatistics, University of Minnesota, Minneapolis, MN 55414.

Reprint requests: David Menge, University of Minnesota, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th St SE, Minneapolis, MN 55455, E-mail: menge023{at}umn.edu.