Impact of Plasmodium falciparum gene deletions on malaria rapid diagnostic test performance

被引:24
|
作者
Gatton, Michelle L. [1 ]
Chaudhry, Alisha [1 ]
Glenn, Jeff [2 ]
Wilson, Scott [2 ]
Ah, Yong [2 ]
Kong, Amy [3 ]
Ord, Rosalynn L. [4 ]
Rees-Channer, Roxanne R. [4 ]
Chiodini, Peter [4 ,5 ]
Incardona, Sandra [6 ]
Cheng, Qin [7 ]
Aidoo, Michael [3 ]
Cunningham, Jane [8 ]
机构
[1] Queensland Univ Technol, Brisbane, Qld, Australia
[2] CDC Fdn, Atlanta, GA USA
[3] Ctr Dis Control & Prevent, Atlanta, GA USA
[4] Hosp Trop Dis, London, England
[5] London Sch Hyg & Trop Med, London, England
[6] Fdn Innovat New Diagnost FIND, Geneva, Switzerland
[7] Australian Def Force Malaria & Infect Dis Inst, Brisbane, Qld, Australia
[8] WHO, Geneva, Switzerland
关键词
Rapid diagnostic tests; Hisidine rich protein 2; HRP2; Gene deletion; HISTIDINE-RICH PROTEIN-2; PARASITES; HRP2;
D O I
10.1186/s12936-020-03460-w
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background Malaria rapid diagnostic tests (RDTs) have greatly improved access to diagnosis in endemic countries. Most RDTs detect Plasmodium falciparum histidine-rich protein 2 (HRP2), but their sensitivity is seriously threatened by the emergence of pfhrp2-deleted parasites. RDTs detecting P. falciparum or pan-lactate dehydrogenase (Pf- or pan-LDH) provide alternatives. The objective of this study was to systematically assess the performance of malaria RDTs against well-characterized pfhrp2-deleted P. falciparum parasites. Methods Thirty-two RDTs were tested against 100 wild-type clinical isolates (200 parasites/mu L), and 40 samples from 10 culture-adapted and clinical isolates of pfhrp2-deleted parasites. Wild-type and pfhrp2-deleted parasites had comparable Pf-LDH concentrations. Pf-LDH-detecting RDTs were also tested against 18 clinical isolates at higher density (2,000 parasites/mu L) lacking both pfhrp2 and pfhrp3. Results RDT positivity against pfhrp2-deleted parasites was highest (> 94%) for the two pan-LDH-only RDTs. The positivity rate for the nine Pf-LDH-detecting RDTs varied widely, with similar median positivity between double-deleted (pfhrp2/3 negative; 63.9%) and single-deleted (pfhrp2-negative/pfhrp3-positive; 59.1%) parasites, both lower than against wild-type P. falciparum (93.8%). Median positivity for HRP2-detecting RDTs against 22 single-deleted parasites was 69.9 and 35.2% for HRP2-only and HRP2-combination RDTs, respectively, compared to 96.0 and 92.5% for wild-type parasites. Eight of nine Pf-LDH RDTs detected all clinical, double-deleted samples at 2,000 parasites/mu L. Conclusions The pan-LDH-only RDTs evaluated performed well. Performance of Pf-LDH-detecting RDTs against wild-type P. falciparum does not necessarily predict performance against pfhrp2-deleted parasites. Furthermore, many, but not all HRP2-based RDTs, detect pfhrp2-negative/pfhrp3-positive samples, with implications for the HRP2-based RDT screening approach for detection and surveillance of HRP2-negative parasites.
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页数:11
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