Plasmodium falciparum histidine-rich proteins 2 (PfHRP2) based RDTs are advocated in falciparum malaria-endemic regions, particularly when quality microscopy is not available. However, diversity and any deletion in the pfhrp2 and pfhrp3 genes can affect the performance of PfHRP2-based RDTs. A total of 400 samples collected from uncomplicated malaria cases from Kenya were investigated for the amino acid repeat profiles in exon 2 of pfhrp2 and pfhrp3 genes. In addition, PfHRP2 levels were measured in 96 individuals with uncomplicated malaria. We observed a unique distribution pattern of amino acid repeats both in the PfHRP2 and PfHRP3. 228 PfHRP2 and 124 PfHRP3 different amino acid sequences were identified. Of this, 214 (94%) PfHRP2 and 81 (65%) PfHRP3 amino acid sequences occurred only once. Thirty-nine new PfHRP2 and 20 new PfHRP3 amino acid repeat types were identified. PfHRP2 levels were not correlated with parasitemia or the number of PfHRP2 repeat types. This study shows the variability of PfHRP2, PfHRP3 and PfHRP2 concentration among uncomplicated malaria cases. These findings will be useful to understand the performance of PfHRP2-based RDTs in Kenya.
In PNAS, Demas et al. (1) show, by long-term in vitro selection using culture-adapted Plasmodium falciparum isolates from Senegal, that the gene encoding the actin-binding protein P. falciparum coronin (pfcoronin) and its genetic variants (G50E, R100K, and E107V) can reduce the susceptibility of the parasite to the active metabolite of the fast-acting antimalarial drug artemisinin, dihydroartemisinin (DHA). Resistance to artemisinins is a global threat in malaria control and elimination efforts (2). Artemisinin resistance, first reported in Southeast Asia and still extremely rare, was associated with the P. falciparum PfKelch13-propeller domain (kelch13 mutations: Y493H, R539T, I543T, and C580Y) (3). PfCoronin, which is structurally similar to Kelch13, is believed to interact with F-actin via its N-terminal propeller domain and to mediate actin organization and motility in merozoites and sporozoites (4, 5). The worldwide map of the occurrence of kelch13, however, indicates absence of the Asian artemisininresistance alleles in Africa (6-8). So far, it is not clear whether the pfcoronin variants G50E, R100K, and E107V occur in natural P. falciparum populations-in particular, in clinical isolates from Africa. We looked at a total of 353 P. falciparum patient isolates that were earlier characterized for the absence of kelch13 gene mutations (7-10) from 4 African countries to verify whether these isolates carry the pfcoronin mutations G50E, R100K, and E107V, which were described by Demas et al. (1) to be associated with reduced susceptibility to DHA. A total of 297 samples
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