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False-Negative Rapid Diagnostic Tests for Malaria and Deletion of the Histidine-Rich Repeat Region of the hrp2 Gene

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  • Mali–Tulane Tropical Medicine Research Center, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako and the National Transfusion Centre, Bamako, Mali; School of Public Health and Tropical Medicine and Center for Infectious Diseases, Tulane University, New Orleans, Louisiana
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We identified 480 persons with positive thick smears for asexual Plasmodium falciparum parasites, of whom 454 had positive rapid diagnostic tests (RDTs) for the histidine-rich protein 2 (HRP2) product of the hrp2 gene and 26 had negative tests. Polymerase chain reaction (PCR) amplification for the histidine-rich repeat region of that gene was negative in one-half (10/22) of false-negative specimens available, consistent with spontaneous deletion. False-negative RDTs were found only in persons with asymptomatic infections, and multiplicities of infection (MOIs) were lower in persons with false-negative RDTs (both P < 0.001). These results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results. The importance of these observations is likely to increase as malaria control improves, because lower MOIs are associated with false-negative RDTs and false-negative RDTs are more frequent in persons with asymptomatic infections. These findings suggest that the use of HRP2-based RDTs should be reconsidered.

Author Notes

*Address correspondence to Donald J. Krogstad, Department of Tropical Medicine and the Center for Infectious Diseases, Tulane University, SL-71, J. Bennett Johnston Building, Room 510, 1430 Tulane Ave., New Orleans, LA 70112. E-mail: krogstad@tulane.edu
†Presented in part at the 46th Annual Meeting of the American Society of Tropical Medicine and Hygiene in Orlando, Florida (December 1997).

Authors' addresses: Ousmane A. Koita, Laboratory of Applied Molecular Biology, Faculty of Science and Techniques, University of Bamako, Bamako, Mali, E-mail: okoita@icermali.org. Ogobara K. Doumbo, Amed Ouattara, Lalla K. Tall, Aoua Konaré, Mahamadou Diakité, Mouctar Diallo, Issaka Sagara, Godfred L. Masinde, Safiatou N. Doumbo, Amagana Dolo, Anatole Tounkara, and Issa Traoré, Mali–Tulane Tropical Medicine Research Center, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako and the National Transfusion Centre, Bamako, Mali, E-mails: okd@icermali.org, aouattara@medicine.umaryland.edu, lallakass@yahoo.com, gafouk@yahoo.fr, mdiakite@icermali.org, mouctard@icermali.org, isagara@icermali.org, sdoumbo@icermali.org, adolo@icermali.org, anatol@icermali.org, and issacely@yahoo.fr. Godfred L. Masinde and Donald J. Krogstad, Department of Tropical Medicine and the Center for Infectious Diseases, Tulane University, New Orleans, LA, E-mail: gmasinde@hotmail.com and krogstad@tulane.edu.

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