Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in a Malaria-Endemic Area of Papua New Guinea

Willie, Nigani; Zimmerman, Peter A.; Mehlotra, Rajeev K.

doi:10.4269/ajtmh.18-0137

Cited by 12 publications

(18 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The AYAHHAHHAAY motif was not detected in this study and HAHHAHHAADAHH occurred at a lower frequency. This is consistent with recent reports by Fontecha et al [31] and Willie et al [40] and corroborates with an earlier report by Lee et al that RDTs which employ the C2-3 and Genway mAbs are less sensitive [32].…”

Section: Discussionsupporting

confidence: 93%

Plasmodium falciparum histidine-rich protein 2 diversity in Ghana

Addai‐Mensah

Dinko

Noagbe

et al. 2020

Malar J

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 93%

Plasmodium falciparum histidine-rich protein 2 diversity in Ghana

Addai‐Mensah

Dinko

Noagbe

et al. 2020

Malar J

View full text Add to dashboard Cite

show abstract

“…The two most frequent epitopes were recognized by the MAbs C1-13 and 3A4. Similar results were reported in a study performed with 120 samples from Papua New Guinea [41]. Given the absence of two motifs (HAHHAHHAADAHH, AYAHHAHHAAY) within the sequences reported here, RDTs using MAbs C2-3 and Genway might be less sensitive, as suggested by Lee et al [23].…”

Section: Discussionsupporting

confidence: 90%

“…A second approach was applied to attempt to correlate the amino acid sequences with the potential capacity of an RDT to detect the PfHRP2 antigen [41]. Eleven epitopes ranging from 8 to 15 amino acids which are recognized by commercially available monoclonal antibodies (MAbs) [23] were searched within the five PfHRP2 patterns and the unique PfHRP3 sequence.…”

Section: Discussionmentioning

confidence: 99%

Genetic variability of Plasmodium falciparum histidine-rich proteins 2 and 3 in Central America

Fontecha

Pinto

Escobar

et al. 2019

Malar J

View full text Add to dashboard Cite

BackgroundMalaria is an important disease in many tropical countries. Rapid diagnostic tests (RDTs) are valuable tools for diagnosing malaria in remote areas. The majority of RDTs used for the diagnosis of Plasmodium falciparum are based on the detection of the specific histidine-rich proteins (PfHRP2 and PfHRP3). During the last decade, the threat posed by the lack of expression of these antigens and the variability of the proteins on the diagnosis of malaria has been widely discussed. The aim of this study was to evaluate the genetic diversity of pfhrp2 and pfhrp3 of P. falciparum isolates collected in three Central American countries.MethodsDNA samples were amplified and sequenced to assess the diversity of nucleotides and amino acids. A search for known epitopes within the amino acid sequence was carried out, and the sensitivity of the sequences was evaluated according to a predictive model. A phylogenetic analysis was carried out including homologous sequences from different regions of the world. Protein structures were predicted in silico.ResultsFive different patterns for PfHRP2 and one pattern for PfHRP3 were identified. Isolates from Central America show a high level of genetic diversity in pfhrp2; however, the amino acid sequences seem to contain enough motifs to be detected by the RDTs currently available.ConclusionIt is unlikely that the variability of the pfhrp2 and pfhrp3 genes has a significant impact on the ability of the RDTs to detect the PfHRP antigens in Central America.Electronic supplementary materialThe online version of this article (10.1186/s12936-019-2668-3) contains supplementary material, which is available to authorized users.

show abstract

“…Specifically, Types 1-10, 12-14, and 19 were found among these isolates. This is in general agreement to a similar report by Willie et al, 2018 [21] using samples collected from Papua New Guinea. They report that Types 1, 2, 6, 7, and 12 were present in almost all ( ≥ 89%) sequences, Types 3, 5, 8, and 10 were present in most ( ≥ 56%) sequences, and Type 4, 13, and 19 were seen in ≤ 33% of sequences.…”

Section: Resultssupporting

confidence: 93%

Modeling Plasmodium falciparum Diagnostic Test Sensitivity using Machine Learning with Histidine-Rich Protein 2 Variants

Ford

Alemayehu

Blackburn

et al. 2020

Preprint

View full text Add to dashboard Cite

Malaria, predominantly caused by Plasmodium falciparum, poses one of largest and most durable health threats in the world. Previously, simplistic regression-based models have been created to characterize malaria infections, though these models often only include a couple genetic factors. Specifically, the Baker et al., 2005 model uses two types of particular repeats in histidine-rich protein 2 (PfHRP2) to assert P. falciparum infection, though the efficacy of this model has waned over recent years due to genetic mutations in the parasite. In this work, we use a dataset of 406 P. falciparum PfHRP2 genetic sequences collected in Ethiopia and derived a larger set of motif repeat matches for use in generating a series of diagnostic machine learning models. Here we show that the usage of additional and different motif repeats proves effective in predicting infection. Furthermore, we use machine learning model explanability methods to highlight which of the repeat types are most important, thereby suggesting potential targets for future versions of rapid diagnostic tests.

show abstract

Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in a Malaria-Endemic Area of Papua New Guinea

Cited by 12 publications

References 35 publications

Plasmodium falciparum histidine-rich protein 2 diversity in Ghana

Plasmodium falciparum histidine-rich protein 2 diversity in Ghana

Genetic variability of Plasmodium falciparum histidine-rich proteins 2 and 3 in Central America

Modeling Plasmodium falciparum Diagnostic Test Sensitivity using Machine Learning with Histidine-Rich Protein 2 Variants

Contact Info

Product

Resources

About