False-negative rapid diagnostic tests for malaria and deletion of the histidine-rich repeat region of the hrp2 gene.
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.
Mali-Tulane Tropical Medicine Research Center, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali. okoita@icermali.org
Ousmane A
OA
Koita
Ogobara K
OK
Doumbo
Amed
A
Ouattara
Lalla K
LK
Tall
Aoua
A
Konaré
Mahamadou
M
Diakité
Mouctar
M
Diallo
Issaka
I
Sagara
Godfred L
GL
Masinde
Safiatou N
SN
Doumbo
Amagana
A
Dolo
Anatole
A
Tounkara
Issa
I
Traoré
Donald J
DJ
Krogstad
D000293:Adolescent; D000349:Africa; D000953:Antigens, Protozoan / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005188:False Negative Reactions; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins