Evolution of pfhrp2 and pfhrp3 deletions in Equatorial Guinea between the pre- and post-RDT introduction.
Africa
False negatives
Malaria
RDT
Subgenus Laverania
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
18 Jul 2024
18 Jul 2024
Historique:
received:
15
04
2024
accepted:
05
07
2024
medline:
19
7
2024
pubmed:
19
7
2024
entrez:
18
7
2024
Statut:
epublish
Résumé
Pfhrp2 and pfhrp3 deletions are threatening Plasmodium falciparum malaria diagnosis by rapid diagnostic tests (RDT) due to false negatives. This study assesses the changes in the frequencies of pfhrp2 and pfhrp3 deletions (pfhrp2 A total of 566 P. falciparum samples were genotyped to assess the presence of pfhrp2 and pfhrp3 deletions and their flanking genes. The specimens were collected 18 years apart from two provinces of Equatorial Guinea, North Bioko (Insular Region) and Litoral Province (Continental Region). Orthologs of pfhrp2 and pfhrp3 genes from other closely related species were used to compare sequencing data to assess pfhrp2 and pfhrp3 evolution. Additionally, population structure was studied using seven neutral microsatellites. This study found that pfhrp2Del and pfhrp3Del were present before the introduction of RDT; however, they increased in frequency after their use, reaching more than 15%. Haplotype networks suggested that pfhrp2Del and pfhrp3Del emerged multiple times. Exon 2 of pfhrp2 and pfhrp3 genes had high variability, but there were no significant changes in amino acid sequences. Baseline sampling before deploying interventions provides a valuable context to interpret changes in genetic markers linked to their efficacy, such as the dynamic of deletions affecting RDT efficacy.
Sections du résumé
BACKGROUND
BACKGROUND
Pfhrp2 and pfhrp3 deletions are threatening Plasmodium falciparum malaria diagnosis by rapid diagnostic tests (RDT) due to false negatives. This study assesses the changes in the frequencies of pfhrp2 and pfhrp3 deletions (pfhrp2
METHODS
METHODS
A total of 566 P. falciparum samples were genotyped to assess the presence of pfhrp2 and pfhrp3 deletions and their flanking genes. The specimens were collected 18 years apart from two provinces of Equatorial Guinea, North Bioko (Insular Region) and Litoral Province (Continental Region). Orthologs of pfhrp2 and pfhrp3 genes from other closely related species were used to compare sequencing data to assess pfhrp2 and pfhrp3 evolution. Additionally, population structure was studied using seven neutral microsatellites.
RESULTS
RESULTS
This study found that pfhrp2Del and pfhrp3Del were present before the introduction of RDT; however, they increased in frequency after their use, reaching more than 15%. Haplotype networks suggested that pfhrp2Del and pfhrp3Del emerged multiple times. Exon 2 of pfhrp2 and pfhrp3 genes had high variability, but there were no significant changes in amino acid sequences.
CONCLUSIONS
CONCLUSIONS
Baseline sampling before deploying interventions provides a valuable context to interpret changes in genetic markers linked to their efficacy, such as the dynamic of deletions affecting RDT efficacy.
Identifiants
pubmed: 39026276
doi: 10.1186/s12936-024-05036-4
pii: 10.1186/s12936-024-05036-4
doi:
Substances chimiques
Protozoan Proteins
0
Antigens, Protozoan
0
HRP3 protein, Plasmodium falciparum
0
HRP-2 antigen, Plasmodium falciparum
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
215Subventions
Organisme : University of Alcalá
ID : FPU-2019
Informations de copyright
© 2024. The Author(s).
Références
WHO. World malaria report 2023. Geneva: World Health Organization; 2023.
Martiáñez-Vendrell X, Skjefte M, Sikka R, Gupta H. Factors affecting the performance of HRP2-based malaria rapid diagnostic tests. Trop Med Infect Dis. 2022;7:265.
pubmed: 36288006
pmcid: 9611031
doi: 10.3390/tropicalmed7100265
la Molina-de Fuente I, Pastor A, Herrador Z, Benito A, Berzosa P. Impact of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions on malaria control worldwide: a systematic review and meta-analysis. Malar J. 2021;20:276.
doi: 10.1186/s12936-021-03812-0
Cook J, Hergott D, Phiri W, Rivas MR, Bradley J, Segura L, et al. Trends in parasite prevalence following 13 years of malaria interventions on Bioko island, Equatorial Guinea: 2004–2016. Malar J. 2018;17:62.
pubmed: 29402288
pmcid: 5799938
doi: 10.1186/s12936-018-2213-9
Berzosa P, González V, Taravillo L, Mayor A, Romay-Barja M, García L, et al. First evidence of the deletion in the pfhrp2 and pfhrp3 genes in Plasmodium falciparum from Equatorial Guinea. Malar J. 2020;19:99.
pubmed: 32122352
pmcid: 7050119
doi: 10.1186/s12936-020-03178-9
Eyong EM, Etutu SJM, Jerome F-C, Nyasa RB, Kwenti TE, Moyeh MN. Plasmodium falciparum histidine-rich protein 2 and 3 gene deletion in the Mount Cameroon region. IJID Reg. 2022;3:300–7.
pubmed: 35755467
pmcid: 9216387
doi: 10.1016/j.ijregi.2022.05.006
Nana RRD, Ngum NL, Makoge V, Amvongo-Adja N, Hawadak J, Singh V. Rapid diagnostic tests for malaria diagnosis in Cameroon: impact of histidine rich protein 2/3 deletions and lactate dehydrogenase gene polymorphism. Diagn Microbiol Infect Dis. 2024;108:116103.
pubmed: 37944271
doi: 10.1016/j.diagmicrobio.2023.116103
Kreidenweiss A, Trauner F, Rodi M, Koehne E, Held J, Wyndorps L, et al. Monitoring the threatened utility of malaria rapid diagnostic tests by novel high-throughput detection of Plasmodium falciparum hrp2 and hrp3 deletions: a cross-sectional, diagnostic accuracy study. EBioMedicine. 2019;50:14–22.
pubmed: 31761619
pmcid: 6921222
doi: 10.1016/j.ebiom.2019.10.048
Bendezu J, Torres K, Villasis E, Incardona S, Bell D, Vinetz J, et al. Geographical distribution and genetic characterization of pfhrp2 negative Plasmodium falciparum parasites in the Peruvian Amazon. PLoS ONE. 2022;17:e0273872.
pubmed: 36413547
pmcid: 9681099
doi: 10.1371/journal.pone.0273872
Alemayehu GS, Blackburn K, Lopez K, Cambel Dieng C, Lo E, Janies D, et al. Detection of high prevalence of Plasmodium falciparum histidine-rich protein 2/3 gene deletions in Assosa zone, Ethiopia: implication for malaria diagnosis. Malar J. 2021;20:109.
pubmed: 33622309
pmcid: 8095343
doi: 10.1186/s12936-021-03629-x
Golassa L, Messele A, Amambua-Ngwa A, Swedberg G. High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia. PLoS ONE. 2020;15:e0241807.
pubmed: 33152025
pmcid: 7644029
doi: 10.1371/journal.pone.0241807
Akinyi S, Hayden T, Gamboa D, Torres K, Bendezu J, Abdallah JF, et al. Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru. Sci Rep. 2013;3:2797.
pubmed: 24077522
pmcid: 3786299
doi: 10.1038/srep02797
Villena FE, Lizewski SE, Joya CA, Valdivia HO. Population genomics and evidence of clonal replacement of Plasmodium falciparum in the Peruvian Amazon. Sci Rep. 2021;11:21212.
pubmed: 34707204
pmcid: 8551272
doi: 10.1038/s41598-021-00806-5
Feleke SM, Reichert EN, Mohammed H, Brhane BG, Mekete K, Mamo H, et al. Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia. Nat Microbiol. 2021;6:1289–99.
pubmed: 34580442
pmcid: 8478644
doi: 10.1038/s41564-021-00962-4
Berhane A, Anderson KF, Mihreteab S, Gresty K, Rogier E, Mohamed S, et al. Major threat to malaria control programs by Plasmodium falciparum lacking histidine-rich protein 2. Eritrea Emerg Infect Dis. 2018;24:462–70.
pubmed: 29460730
doi: 10.3201/eid2403.171723
Gibbons J, Qin J, Malla P, Wang Z, Brashear A, Wang C, et al. Lineage-specific expansion of Plasmodium falciparum parasites with pfhrp2 deletion in the Greater Mekong Subregion. J Infect Dis. 2020;222:1561–9.
pubmed: 32386321
pmcid: 7529045
doi: 10.1093/infdis/jiaa250
Baker J, Ho M-F, Pelecanos A, Gatton M, Chen N, Abdullah S, et al. Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests. Malar J. 2010;9:129.
pubmed: 20470441
pmcid: 2893195
doi: 10.1186/1475-2875-9-129
Baker J, McCarthy J, Gatton M, Kyle DE, Belizario V, Luchavez J, et al. Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests. J Infect Dis. 2005;192:870–7.
pubmed: 16088837
doi: 10.1086/432010
Lee N, Gatton ML, Pelecanos A, Bubb M, Gonzalez I, Bell D, et al. Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3. J Clin Microbiol. 2012;50:1397–405.
pubmed: 22259210
pmcid: 3318543
doi: 10.1128/JCM.06533-11
Roche J, Guerra-Neira A, Raso J, Benito A. Surveillance of in vivo resistance of Plasmodium falciparum to antimalarial drugs from 1992 to 1999 in Malabo (Equatorial Guinea). Am J Trop Med Hyg. 2003;68:598–601.
pubmed: 12812353
doi: 10.4269/ajtmh.2003.68.598
Riloha Rivas M, Warsame M, Mbá Andeme R, Nsue Esidang S, Ncogo PR, Phiri WP, et al. Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine and polymorphism in Plasmodium falciparum kelch13-propeller gene in Equatorial Guinea. Malar J. 2021;20:275.
pubmed: 34158055
pmcid: 8220721
doi: 10.1186/s12936-021-03807-x
Berzosa P, de la Molina Fuente I, Ta-Tang T-H, González V, García L, Rodríguez-Galet A, et al. Temporal evolution of the resistance genotypes of Plasmodium falciparum in isolates from Equatorial Guinea during 20 years (1999 to 2019). Malar J. 2021;20:463.
pubmed: 34906159
pmcid: 8670137
doi: 10.1186/s12936-021-04000-w
de la Molina Fuente I, Yimar M, García L, González V, Amor A, Anegagrie M, et al. Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia. Malar J. 2022;21:287.
doi: 10.1186/s12936-022-04306-3
Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–402.
pubmed: 9254694
pmcid: 146917
doi: 10.1093/nar/25.17.3389
PlasmoDB. https://plasmodb.org/plasmo/app
Gouy M, Guindon S, Gascuel O. SeaView version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol Biol Evol. 2010;27:221–4.
pubmed: 19854763
doi: 10.1093/molbev/msp259
Ronquist F, Huelsenbeck JP. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics. 2003;19:1572–4.
pubmed: 12912839
doi: 10.1093/bioinformatics/btg180
IQ-TREE: Efficient phylogenomic software by maximum likelihood. http://www.iqtree.org/
FigTree. http://tree.bio.ed.ac.uk/software/figtree/
Prosser C, Gresty K, Ellis J, Meyer W, Anderson K, Lee R, et al. Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions in strains from Nigeria, Sudan, and South Sudan. Emerg Infect Dis. 2021;27:471–9.
pubmed: 33496220
pmcid: 7853540
doi: 10.3201/eid2702.191410
Anderson TJ, Haubold B, Williams JT, Estrada-Franco JG, Richardson L, Mollinedo R, et al. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol. 2000;17:1467–82.
pubmed: 11018154
doi: 10.1093/oxfordjournals.molbev.a026247
Nei M. Analysis of gene diversity in subdivided populations. Proc Natl Acad Sci USA. 1973;70:3321–3.
pubmed: 4519626
pmcid: 427228
doi: 10.1073/pnas.70.12.3321
Eliades N-G, Eliades DG. HAPLOTYPE ANALYSIS: Software for analysis of haplotype data. Distributed by the authors. Forest Genetics and Forest Tree Breeding, Georg-August University Goettingen, Germany. https://www.uni-goettingen.de/en/134935.html
Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000;155:945–59.
pubmed: 10835412
pmcid: 1461096
doi: 10.1093/genetics/155.2.945
Earl DA, von Holdt BM. STRUCTURE HARVESTER: a website and program for visualizing STRUCTURE output and implementing the Evanno method. Conserv Genet Resour. 2012. https://doi.org/10.1007/s12686-011-9548-7 .
doi: 10.1007/s12686-011-9548-7
Jakobsson M, Rosenberg NA. CLUMPP: a cluster matching and permutation program for dealing with label switching and multimodality in analysis of population structure. Bioinformatics. 2007;23:1801–6.
pubmed: 17485429
doi: 10.1093/bioinformatics/btm233
Rosenberg NA. distruct: a program for the graphical display of population structure. Mol Ecol Notes. 2004. https://doi.org/10.1046/j.1471-8286.2003.00566.x .
doi: 10.1046/j.1471-8286.2003.00566.x
Francisco AP, Bugalho M, Ramirez M, Carriço JA. Global optimal eBURST analysis of multilocus typing data using a graphic matroid approach. BMC Bioinformatics. 2009;10:152.
pubmed: 19450271
pmcid: 2705362
doi: 10.1186/1471-2105-10-152
Francisco AP, Vaz C, Monteiro PT, Melo-Cristino J, Ramirez M, Carriço JA. PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics. 2012;13:87.
pubmed: 22568821
pmcid: 3403920
doi: 10.1186/1471-2105-13-87
Nderu D, Kimani F, Karanja E, Thiong’o K, Akinyi M, Too E, et al. Genetic diversity and population structure of Plasmodium falciparum in Kenyan-Ugandan border areas. Trop Med Int Health. 2019;24:647–56.
pubmed: 30816614
doi: 10.1111/tmi.13223
Pacheco MA, Matta NE, Valkiunas G, Parker PG, Mello B, Stanley CE, et al. Mode and rate of evolution of Haemosporidian mitochondrial genomes: timing the radiation of avian parasites. Mol Biol Evol. 2018;35:383–403.
pubmed: 29126122
doi: 10.1093/molbev/msx285
de Bruin D, Lanzer M, Ravetch JV. The polymorphic subtelomeric regions of Plasmodium falciparum chromosomes contain arrays of repetitive sequence elements. Proc Natl Acad Sci USA. 1994;91:619–23.
pubmed: 8290573
pmcid: 43000
doi: 10.1073/pnas.91.2.619
Watson OJ, Tran TN-A, Zupko RJ, Symons T, Thomson R, Visser T, et al. Global risk of selection and spread of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions. medRxiv. 2023. https://doi.org/10.1101/2023.10.21.23297352 .
doi: 10.1101/2023.10.21.23297352
pubmed: 37745576
pmcid: 10275003
Watson OJ, Slater HC, Verity R, Parr JB, Mwandagalirwa MK, Tshefu A, et al. Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa. Elife. 2017;6:e25008.
pubmed: 28837020
pmcid: 5602420
doi: 10.7554/eLife.25008
Chang H-H, Moss EL, Park DJ, Ndiaye D, Mboup S, Volkman SK, et al. Malaria life cycle intensifies both natural selection and random genetic drift. Proc Natl Acad Sci USA. 2013;110:20129–34.
pubmed: 24259712
pmcid: 3864301
doi: 10.1073/pnas.1319857110
Escalante AA, Pacheco MA. Malaria molecular epidemiology: an evolutionary genetics perspective. Microbiol Spectr. 2019. https://doi.org/10.1128/microbiolspec.ame-0010-2019 .
doi: 10.1128/microbiolspec.ame-0010-2019
pubmed: 31400095
pmcid: 6690375
Molina-de la Fuente I, Benito MJS, Flevaud L, Ousley J, Pasquale HA, Julla A, et al. Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in malaria-hyperendemic region South Sudan. Emerg Infect Dis. 2023;29:154–9.
pubmed: 36573593
pmcid: 9796199
doi: 10.3201/eid2901.220775
Nair S, Li X, Nkhoma SC, Anderson T. Fitness costs of pfhrp2 and pfhrp3 deletions underlying diagnostic evasion in malaria parasites. J Infect Dis. 2022;226:1637–45.
pubmed: 35709327
pmcid: 10205895
doi: 10.1093/infdis/jiac240
Sepúlveda N, Phelan J, Diez-Benavente E, Campino S, Clark TG, Hopkins H, et al. Global analysis of Plasmodium falciparum histidine-rich protein-2 (pfhrp2) and pfhrp3 gene deletions using whole-genome sequencing data and meta-analysis. Infect Genet Evol. 2018;62:211–9.
pubmed: 29729386
doi: 10.1016/j.meegid.2018.04.039
Markwalter CF, Mudenda L, Leelawong M, Kimmel DW, Nourani A, Mbambara S, et al. Evidence for histidine-rich protein 2 immune complex formation in symptomatic patients in Southern Zambia. Malar J. 2018;17:256.
pubmed: 29986725
pmcid: 6038308
doi: 10.1186/s12936-018-2400-8