Evaluation of the sensitivity of a pLDH-based and an aldolase-based rapid diagnostic test for diagnosis of uncomplicated and severe malaria caused by PCR-confirmed Plasmodium knowlesi, Plasmodium falciparum, and Plasmodium vivax.
Plasmodium knowlesi can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all Plasmodium species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal Plasmodium species, using a pan-Plasmodium lactate dehydrogenase (pLDH)-P. falciparum histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-Plasmodium aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed Plasmodium monoinfection, the sensitivity of the pLDH component of the pLDH-PfHRP2 RDT was 74% (95/129; 95% confidence interval [CI], 65 to 80%), 91% (110/121; 95% CI, 84 to 95%), and 95% (41/43; 95% CI, 85 to 99%) for PCR-confirmed P. knowlesi, P. falciparum, and P. vivax infections, respectively, and 88% (30/34; 95% CI, 73 to 95%), 90% (38/42; 95% CI, 78 to 96%), and 100% (12/12; 95% CI, 76 to 100%) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95% (36/38; 95% CI, 83 to 99), 100% (13/13; 95% CI, 77 to 100), and 100% (7/7; 95% CI, 65 to 100%), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all Plasmodium species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for P. knowlesi. More sensitive RDTs are needed in regions of P. knowlesi endemicity.
Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
Bridget E
BE
Barber
Timothy
T
William
Matthew J
MJ
Grigg
Kim
K
Piera
Tsin W
TW
Yeo
Nicholas M
NM
Anstey
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000953:Antigens, Protozoan / Q000235:genetics; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D008288:Malaria / Q000175:diagnosis* / Q000469:parasitology; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D010274:Parasitology / Q000379:methods; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D016790:Plasmodium knowlesi / Q000302:isolation & purification*; D010966:Plasmodium vivax / Q000302:isolation & purification*; D015800:Protozoan Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D062606:Tertiary Care Centers; D055815:Young Adult
D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D007770:L-Lactate Dehydrogenase; D005634:Fructose-Bisphosphate Aldolase