Plasmodium falciparum histidine-rich protein 2 diversity in Ghana

Abstract

Background: In the absence of microscopy, Plasmodium falciparum histidine-rich proteins 2 (PfHRP2)-based rapid diagnostic tests (RDTs) are recommended for the diagnosis of falciparum malaria, particularly in endemic regions. However, genetic variability of the pfhrp2 gene threatens the usefulness of the test due to its impact on RDT sensitivity. This study aimed to investigate the diversity of pfhrp2 in malaria cases among children in Ghana. Methods: A cross-sectional study was conducted at the Adidome Government Hospital in the Volta Region of Ghana. A total of 50 children with mean age of 6.6 ± 3.5 years and diagnosed falciparum malaria were included. Blood samples were collected for complete blood count, malaria parasite identification and counting using auto analyzer and microscopy, respectively. DNA was isolated from blood-spotted Whatman filters, amplified and sequenced. Nucleotide sequences were translated in silico to corresponding amino acids and the deduced amino acids sequences were analyzed for diversity using Mega X. Results: The number of repeats and number of each repeat within PfHRP2 varied between isolates. Twelve rare PfHRP2 repeat types, two of which are previously unreported, were identified in this study. The HRP2 sequence obtained in this study shared high similarities with isolates from Kenya. Using Baker's regression model, Group B was the highest occurring type (58.0%). Screening of all sequences for epitopes recognized by PfHRP2-specific monoclonal antibodies (mAbs), the predominant motif was AHHAADAHH, which is recognized by the C1-13 mAbs. Conclusion: This study reports diversity of P. falciparum HRP2 in samples from Ghanaian children with symptomatic malaria. The findings of this study highlight the existence of extra amino acid repeat types which adds to the PfHRP2 antigenic variability.

Genetic Variations of Plasmodium Falciparum Histidine-rich Protein 2 and 3 in Assosa Zone, Ethiopia: Its Impact on the Performance of Malaria Rapid Diagnostic Tests

“…On the contrary, PfHRP2 repeat types obtained within this study showed certain difference from African and global reports in a number of ways. First, PfHRP2 type 12 repeat was found in a few isolates (10.5%) this did not align with previous studies from Kenya [30], Ghana [31]and central America [36]. However, studies from Senegal [34] showed the presence of type 12 repeats in a few isolates similar to the present study.…”

“…The ndings of PfHRP3 repeat types in the present study are consistent with previous reports from Kenya [30], Yemen [29], Ghana [31], and globally [8]. On the other hand, type 2 repeat was absent in all isolates of PfHRP3 sequence in Ethiopia as well as other parts of Africa [29][30][31], but type 2 repeat has been reported in PfHRP3 in few isolates from Kenya [30] and India [32]. This variation observed in PfHRP2 and PfHRP3 repeat types might be due to differences in geographical and transmission settings [8,38,39], frequency of exposure of drug and level of immunity of study participants [40,41], clinical versus asymptomatic study participants, and methods used for molecular analysis.…”

“…The structural organization of PfHRP2 amino acid sequences was less conserved than PfHRP3 among the Ethiopia isolates. The sequence length and the number of amino acid repeat types of PfHRP2 and PfHRP3 in this study were comparable to those previously reported in Yemen [29] and Madagascar [16], but lower than those in Kenya [30] and Ghana [31] and higher than in India [32].…”

“…Eleven different PfHRP2 repeats and eight different PfHRP3 repeats were found at Sherkole, Bambasi, Kurmuk and Assosa with slight difference in the frequency of the repeat type within and between P. falciparum isolates in Ethiopia, similar to those reported in Africa [30,31] and worldwide [8]. The PfHRP2 repeat types observed in the present study were previously reported in Africa [29][30][31], Asia [8,32], and America [35,36].…”

Genetic diversity and genetic relatedness in Plasmodium falciparum parasite population in individuals with uncomplicated malaria based on microsatellite typing in Eastern and Western regions of Uganda, 2019–2020

“…Despite recent advances in genome sequencing of malaria parasites, microsatellite markers remain an important source of data to understand the genetic diversity and relatedness of parasite populations and understanding of transmission dynamics [ 15 , 21 , 22 , 32 , 33 , 48 – 51 ]. In this study, the genetic relatedness among monoclonal Ugandan parasites and between monoclonal Ugandan and Eritrean parasites was investigated using 7-microsatellite-marker haplotypes.…”