Genetic polymorphism and evidence of signatures of selection in the Plasmodium falciparum circumsporozoite protein gene in Tanzanian regions with different malaria endemicity.
Circumsporozoite protein
Plasmodium falciparum
Genetic diversity
Malaria vaccine
Signature of selection
Tanzania
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
08 May 2024
08 May 2024
Historique:
received:
31
01
2024
accepted:
03
05
2024
medline:
9
5
2024
pubmed:
9
5
2024
entrez:
9
5
2024
Statut:
epublish
Résumé
In 2021 and 2023, the World Health Organization approved RTS,S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of Plasmodium falciparum circumsporozoite protein (PfCSP), but polymorphisms in the gene raise concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the Pfcsp genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission intensities in Mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country. The analysis involved 589 whole genome sequences generated by and as part of the MalariaGEN Community Project. The samples were collected between 2013 and January 2015 from five regions of Mainland Tanzania: Morogoro and Tanga (Muheza) (moderate transmission areas), and Kagera (Muleba), Lindi (Nachingwea), and Kigoma (Ujiji) (high transmission areas). Wright's inbreeding coefficient (F Based on F The findings demonstrate high diversity of the Pfcsp gene with limited population differentiation. The Pfcsp gene showed positive Tajima's D values, consistent with balancing selection for variants within Th2R and Th3R regions. The study observed differences between the intended haplotypes incorporated into the design of RTS,S and R21 vaccines and those present in natural parasite populations. Therefore, additional research is warranted, incorporating other regions and more recent data to comprehensively assess trends in genetic diversity within this important gene. Such insights will inform the choice of alleles to be included in the future vaccines.
Sections du résumé
BACKGROUND
BACKGROUND
In 2021 and 2023, the World Health Organization approved RTS,S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of Plasmodium falciparum circumsporozoite protein (PfCSP), but polymorphisms in the gene raise concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the Pfcsp genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission intensities in Mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country.
METHODS
METHODS
The analysis involved 589 whole genome sequences generated by and as part of the MalariaGEN Community Project. The samples were collected between 2013 and January 2015 from five regions of Mainland Tanzania: Morogoro and Tanga (Muheza) (moderate transmission areas), and Kagera (Muleba), Lindi (Nachingwea), and Kigoma (Ujiji) (high transmission areas). Wright's inbreeding coefficient (F
RESULTS
RESULTS
Based on F
CONCLUSIONS
CONCLUSIONS
The findings demonstrate high diversity of the Pfcsp gene with limited population differentiation. The Pfcsp gene showed positive Tajima's D values, consistent with balancing selection for variants within Th2R and Th3R regions. The study observed differences between the intended haplotypes incorporated into the design of RTS,S and R21 vaccines and those present in natural parasite populations. Therefore, additional research is warranted, incorporating other regions and more recent data to comprehensively assess trends in genetic diversity within this important gene. Such insights will inform the choice of alleles to be included in the future vaccines.
Identifiants
pubmed: 38720288
doi: 10.1186/s12936-024-04974-3
pii: 10.1186/s12936-024-04974-3
doi:
Substances chimiques
circumsporozoite protein, Protozoan
0
Protozoan Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
139Subventions
Organisme : Bill & Melinda Gates Foundation
ID : 02202
Pays : United States
Informations de copyright
© 2024. The Author(s).
Références
WHO. World malaria report 2021. Geneva: World Health Organization; 2021.
WHO. World Malaria Report 2022. Geneva: World Health Organization; 2022. https://apps.who.int/iris/rest/bitstreams/1484818/retrieve . Accessed 10 Dec 2022.
Mitchell CL, Ngasala B, Janko MM, Chacky F, Edwards JK, Pence BW, et al. Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children. Malar J. 2022;21:80.
pubmed: 35264152
pmcid: 8905829
doi: 10.1186/s12936-022-04107-8
WHO. Global technical strategy for malaria. Geneva: World Health Organization; 2021.
Feachem RGA, Chen I, Akbari O, Bertozzi-Villa A, Bhatt S, Binka F, et al. Malaria eradication within a generation: ambitious, achievable, and necessary. Lancet. 2019;394:1056–112.
pubmed: 31511196
doi: 10.1016/S0140-6736(19)31139-0
Dhiman S. Are malaria elimination efforts on right track? An analysis of gains achieved and challenges ahead. Infect Dis Poverty. 2019;8:14.
pubmed: 30760324
pmcid: 6375178
doi: 10.1186/s40249-019-0524-x
Guyant P, Corbel V, Guérin PJ, Lautissier A, Nosten F, Boyer S, et al. Past and new challenges for malaria control and elimination: the role of operational research for innovation in designing interventions. Malar J. 2015;14:279.
pubmed: 26185098
pmcid: 4504133
doi: 10.1186/s12936-015-0802-4
Huang H-Y, Liang X-Y, Lin L-Y, Chen J-T, Ehapo CS, Eyi UM, et al. Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis. Malar J. 2020;19:245.
pubmed: 32660484
pmcid: 7359586
doi: 10.1186/s12936-020-03315-4
Casares S, Brumeanu T-D, Richie TL. The RTS, S malaria vaccine. Vaccine. 2010;28:4880–94.
pubmed: 20553771
doi: 10.1016/j.vaccine.2010.05.033
Koff WC, Gust ID, Plotkin SA. Toward a human vaccines project. Nat Immunol. 2014;15:589–92.
pubmed: 24940943
doi: 10.1038/ni.2871
Nadeem AY, Shehzad A, Islam SU, Al-Suhaimi EA, Lee YS. Mosquirix™ RTS, S/AS01 vaccine development, immunogenicity, and efficacy. Vaccines (Basel). 2022;10:713.
pubmed: 35632469
doi: 10.3390/vaccines10050713
Duffy PE, Patrick GJ. Malaria vaccines since 2000: progress, priorities, products. NPJ Vaccines. 2020;5:48.
pubmed: 32566259
pmcid: 7283239
doi: 10.1038/s41541-020-0196-3
Le Roch KG, Chung DWD, Ponts N. Genomics and integrated systems biology in Plasmodium falciparum: a path to malaria control and eradication. Parasite Immunol. 2012;34:50–60.
pubmed: 21995286
pmcid: 3265687
doi: 10.1111/j.1365-3024.2011.01340.x
Mohamed NS, AbdElbagi H, Elsadig AR, Ahmed AE, Mohammed YO, Elssir LT, et al. Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS, S leading malaria vaccine candidate. Malar J. 2021;20:436.
pubmed: 34758827
pmcid: 8579544
doi: 10.1186/s12936-021-03971-0
Kurtovic L, Drew DR, Dent AE, Kazura JW, Beeson JG. Antibody targets and properties for complement-fixation against the circumsporozoite protein in malaria immunity. Front Immunol. 2021;12: 775659.
pubmed: 34925347
pmcid: 8671933
doi: 10.3389/fimmu.2021.775659
WHO. Guidelines for malaria. Geneva: World Health Organization; 2022.
Stoute JA, Slaoui M, Heppner DG, Momin P, Kester KE, Desmons P, et al. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria RTS, S. Malaria Vaccine Evaluation Group. N Engl J Med. 1997;336:86–91.
pubmed: 8988885
doi: 10.1056/NEJM199701093360202
Regules JA, Cummings JF, Ockenhouse CF. The RTS, S vaccine candidate for malaria. Expert Rev Vaccines. 2011;10:589–99.
pubmed: 21604980
doi: 10.1586/erv.11.57
Asante KP, Abdulla S, Agnandji S, Lyimo J, Vekemans J, Soulanoudjingar S, et al. Safety and efficacy of the RTS, S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial. Lancet Infect Dis. 2011;11:741–9.
pubmed: 21782519
doi: 10.1016/S1473-3099(11)70100-1
Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, Kester KE, et al. Efficacy of RTS, S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet. 2001;358:1927–34.
pubmed: 11747915
doi: 10.1016/S0140-6736(01)06957-4
Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, et al. Safety of the RTS, S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet. 2007;370:1543–51.
pubmed: 17949807
doi: 10.1016/S0140-6736(07)61542-6
RTS,S Clinical Trials Partnership. Efficacy and safety of RTS, S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. 2015;386:31–45.
doi: 10.1016/S0140-6736(15)60721-8
Asante KP, Adjei G, Enuameh Y, Owusu-Agyei S. RTS, S malaria vaccine development: progress and considerations for postapproval introduction. Vaccine Dev Ther. 2016;6:25–52.
doi: 10.2147/VDT.S53028
Collins KA, Snaith R, Cottingham MG, Gilbert SC, Hill AVS. Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine. Sci Rep. 2017;7:46621.
pubmed: 28422178
pmcid: 5395940
doi: 10.1038/srep46621
Ballou WR, Rothbard J, Wirtz RA, Gordon DM, Williams JS, Gore RW, et al. Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum. Science. 1985;228:996–9.
pubmed: 2988126
doi: 10.1126/science.2988126
Datoo MS, Natama MH, Somé A, Traoré O, Rouamba T, Bellamy D, et al. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021;397:1809–18.
pubmed: 33964223
pmcid: 8121760
doi: 10.1016/S0140-6736(21)00943-0
Datoo MS, Dicko A, Tinto H, Ouédraogo JB, Hamaluba M, Olotu A, Beaumont E, Ramos-Lopez F, Magloire Natama H, Weston S, et al. A Phase III Randomised Controlled Trial Evaluating the Malaria Vaccine Candidate R21/Matrix-M™ in African Children. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4584076 .
Neafsey DE, Juraska M, Bedford T, Benkeser D, Valim C, Griggs A, et al. Genetic diversity and protective efficacy of the RTS, S/AS01 malaria vaccine. N Engl J Med. 2015;373(21):2025–37.
pubmed: 26488565
pmcid: 4762279
doi: 10.1056/NEJMoa1505819
Chaudhury S, MacGill RS, Early AM, Bolton JS, King CR, Locke E, et al. Breadth of humoral immune responses to the C-terminus of the circumsporozoite protein is associated with protective efficacy induced by the RTS,S malaria vaccine. Vaccine. 2021;39:968–75.
pubmed: 33431225
doi: 10.1016/j.vaccine.2020.12.055
Pinzon-Ortiz C, Friedman J, Esko J, Sinnis P. The binding of the circumsporozoite protein to cell surface heparan sulfate proteoglycans is required for plasmodium sporozoite attachment to target cells. J Biol Chem. 2001;276:26784–91.
pubmed: 11352923
doi: 10.1074/jbc.M104038200
Rathore D, Sacci JB, de la Vega P, McCutchan TF. Binding and invasion of liver cells by Plasmodium falciparum sporozoites. Essential involvement of the amino terminus of circumsporozoite protein. J Biol Chem. 2002;277:7092–8.
pubmed: 11751898
doi: 10.1074/jbc.M106862200
Gandhi K, Thera MA, Coulibaly D, Traoré K, Guindo AB, Ouattara A, et al. Variation in the circumsporozoite protein of Plasmodium falciparum: vaccine development implications. PLoS ONE. 2014;9: e101783.
pubmed: 24992338
pmcid: 4081809
doi: 10.1371/journal.pone.0101783
Gandhi K, Thera MA, Coulibaly D, Traoré K, Guindo AB, Doumbo OK, et al. Next generation sequencing to detect variation in the Plasmodium falciparum circumsporozoite protein. Am J Trop Med Hyg. 2012;86:775–81.
pubmed: 22556073
pmcid: 3335679
doi: 10.4269/ajtmh.2012.11-0478
Egan JE, Hoffman SL, Haynes JD, Sadoff JC, Schneider I, et al. Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 1993;49:166–73.
pubmed: 8357078
doi: 10.4269/ajtmh.1993.49.166
Plassmeyer ML, Reiter K, Shimp RL, Kotova S, Smith PD, Hurt DE, et al. Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate. J Biol Chem. 2009;284:26951–63.
pubmed: 19633296
pmcid: 2785382
doi: 10.1074/jbc.M109.013706
Barry AE, Schultz L, Buckee CO, Reeder JC. Contrasting population structures of the genes encoding ten leading vaccine-candidate antigens of the human malaria parasite Plasmodium falciparum. PLoS ONE. 2009;4: e8497.
pubmed: 20041125
pmcid: 2795866
doi: 10.1371/journal.pone.0008497
Zeeshan M, Alam MT, Vinayak S, Bora H, Tyagi RK, Alam MS, et al. Genetic variation in the Plasmodium falciparum circumsporozoite protein in India and its relevance to RTS,S malaria vaccine. PLoS ONE. 2012;7: e43430.
pubmed: 22912873
pmcid: 3422267
doi: 10.1371/journal.pone.0043430
Lê HG, Kang J-M, Moe M, Jun H, Thái TL, Lee J, et al. Genetic polymorphism and natural selection of circumsporozoite surface protein in Plasmodium falciparum field isolates from Myanmar. Malar J. 2018;17:361.
pubmed: 30314440
pmcid: 6186114
doi: 10.1186/s12936-018-2513-0
Ishengoma D, Shayo A, Mandara C, Baraka V, Madebe R, Ngatunga, et al. The role of malaria rapid diagnostic tests in screening of patients to be enrolled in clinical trials in low malaria transmission settings. Health Syst Policy Res. 2016;3:2.
Ahouidi A, Ali M, Almagro-garcia J, Amambua-ngwa A, Amaratunga C, MalariaGEN, et al. An open dataset of Plasmodium falciparum genome variation in 7000 worldwide samples. Wellcome Open Res. 2021;6:42.
pubmed: 33824913
pmcid: 8008441
doi: 10.12688/wellcomeopenres.16168.1
Ghansah A, Amenga-Etego L, Amambua-Ngwa A, Andagalu B, Apinjoh T, Bouyou-Akotet M, et al. Monitoring parasite diversity for malaria elimination in sub-Saharan Africa. Science. 2014;345:1297–8.
pubmed: 25214619
pmcid: 4541720
doi: 10.1126/science.1259423
Shayo A, Mandara CI, Shahada F, Buza J, Lemnge MM, Ishengoma DS. Therapeutic efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in North-Eastern Tanzania. Malar J. 2014;13:376.
pubmed: 25240962
pmcid: 4177150
doi: 10.1186/1475-2875-13-376
Mandara CI, Kavishe RA, Gesase S, Mghamba J, Ngadaya E, Mmbuji P, et al. High efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Muheza and Kigoma Districts, Tanzania. Malar J. 2018;17:261.
pubmed: 29996849
pmcid: 6042436
doi: 10.1186/s12936-018-2409-z
Venkatesan M, Amaratunga C, Campino S, Auburn S, Koch O, Lim P, et al. Using CF11 cellulose columns to inexpensively and effectively remove human DNA from Plasmodium falciparum-infected whole blood samples. Malar J. 2012;11:41.
pubmed: 22321373
pmcid: 3295709
doi: 10.1186/1475-2875-11-41
MalariaGEN. Pf7: an open dataset of Plasmodium falciparum genome. Wellcome Open Res. 2023;8:22.
pmcid: 9971654
doi: 10.12688/wellcomeopenres.18681.1
Jung Y, Han D. BWA-MEME: BWA-MEM emulated with a machine learning approach. BioRxiv. 2021.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.
pubmed: 17701901
pmcid: 1950838
doi: 10.1086/519795
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303.
pubmed: 20644199
pmcid: 2928508
doi: 10.1101/gr.107524.110
Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J, Maslen G, et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature. 2012;487:375–9.
pubmed: 22722859
pmcid: 3738909
doi: 10.1038/nature11174
Lee S, Harrison A, Tessier N, Tavul L, Miotto O. Assessing clonality in malaria parasites from massively parallel sequencing data. F1000Research. 2015;4:1043.
Chakraborty R, Danker-Hopfe H. Analysis of population structure: a comparative study of different estimators of wright’s fixation indices. In: Rao CR, Chakraborty R, editors. Handbook of statistics, vol. 8. Elsevier; 1991. p. 203–54.
Rozas J, Ferrer-Mata A, Sánchez-DelBarrio JC, Guirao-Rico S, Librado P, Ramos-Onsins SE, et al. Dnasp 6: DNA sequence polymorphism analysis of large data sets. Mol Biol Evol. 2017;34:3299–302.
pubmed: 29029172
doi: 10.1093/molbev/msx248
Bandelt HJ, Forster P, Röhl A. Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol. 1999;16:37–48.
pubmed: 10331250
doi: 10.1093/oxfordjournals.molbev.a026036
Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The variant call format and VCFtools. Bioinformatics. 2011;27:2156–8.
pubmed: 21653522
pmcid: 3137218
doi: 10.1093/bioinformatics/btr330
Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989;123:585–95.
pubmed: 2513255
pmcid: 1203831
doi: 10.1093/genetics/123.3.585
Fu YX, Li WH. Statistical tests of neutrality of mutations. Genetics. 1993;133:693–709.
pubmed: 8454210
pmcid: 1205353
doi: 10.1093/genetics/133.3.693
Tamura K, Stecher G, Kumar S. MEGA11: molecular evolutionary genetics analysis version 11. Mol Biol Evol. 2021;38:3022–7.
pubmed: 33892491
pmcid: 8233496
doi: 10.1093/molbev/msab120
Thawer SG, Chacky F, Runge M, Reaves E, Mandike R, Lazaro S, et al. Sub-national stratification of malaria risk in mainland Tanzania: a simplified assembly of survey and routine data. Malar J. 2020;19:177.
pubmed: 32384923
pmcid: 7206674
doi: 10.1186/s12936-020-03250-4
Ministry of Health, Community Development, Gender, Elderly and Children. National Malaria Strategic Plan 2021–2025, Transitioning to malaria elimination in phases. National Malaria Control Programme, Tanzania, 2021.
World Health Organization. WHO recommends R21/Matrix-M vaccine for malaria prevention in updated advice on immunization. Geneva: World Health Organization; 2023.
Aragam NR, Thayer KM, Nge N, Hoffman I, Martinson F, Kamwendo D, et al. Diversity of T cell epitopes in Plasmodium falciparum circumsporozoite protein likely due to protein-protein interactions. PLoS ONE. 2013;8: e62427.
pubmed: 23667476
pmcid: 3646838
doi: 10.1371/journal.pone.0062427
Pringle JC, Wesolowski A, Berube S, Kobayashi T, Gebhardt ME, Mulenga M, et al. High Plasmodium falciparum genetic diversity and temporal stability despite control efforts in high transmission settings along the international border between Zambia and the Democratic Republic of the Congo. Malar J. 2019;18:400.
pubmed: 31801548
pmcid: 6894251
doi: 10.1186/s12936-019-3023-4
Amegashie EA, Amenga-Etego L, Adobor C, Ogoti P, Mbogo K, Amambua-Ngwa A, et al. Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in Ghana. Malar J. 2020;19:437.
pubmed: 33246470
pmcid: 7694917
doi: 10.1186/s12936-020-03510-3
He Z-Q, Zhang Q-Q, Wang D, Hu Y-B, Zhou R-M, Qian D, et al. Genetic polymorphism of circumsporozoite protein of Plasmodium falciparum among Chinese migrant workers returning from Africa to Henan Province. Malar J. 2022;21:248.
pubmed: 36030242
pmcid: 9419638
doi: 10.1186/s12936-022-04275-7
Duffy CW, Ba H, Assefa S, Ahouidi AD, Deh YB, Tandia A, et al. Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution. Mol Ecol. 2017;26:2880–94.
pubmed: 28214367
pmcid: 5485074
doi: 10.1111/mec.14066
Amambua-Ngwa A, Tetteh KKA, Manske M, Gomez-Escobar N, Stewart LB, Deerhake ME, et al. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites. PLoS Genet. 2012;8: e1002992.
pubmed: 23133397
pmcid: 3486833
doi: 10.1371/journal.pgen.1002992
Pringle JC, Carpi G, Almagro-Garcia J, Zhu SJ, Kobayashi T, Mulenga M, et al. RTS, S/AS01 malaria vaccine mismatch observed among Plasmodium falciparum isolates from southern and central Africa and globally. Sci Rep. 2018;8:6622.
pubmed: 29700348
pmcid: 5920075
doi: 10.1038/s41598-018-24585-8
Bailey JA, Mvalo T, Aragam N, Weiser M, Congdon S, Kamwendo D, et al. Use of massively parallel pyrosequencing to evaluate the diversity of and selection on Plasmodium falciparum csp T-cell epitopes in Lilongwe. Malawi J Infect Dis. 2012;206:580–7.
pubmed: 22551816
doi: 10.1093/infdis/jis329
Polley SD, Conway DJ. Strong diversifying selection on domains of the Plasmodium falciparum apical membrane antigen 1 gene. Genetics. 2001;158:1505–12.
pubmed: 11514442
pmcid: 1461755
doi: 10.1093/genetics/158.4.1505
Nirmolia T, Ahmed MA, Sathishkumar V, Sarma NP, Bhattacharyya DR, Mohapatra PK, et al. Genetic diversity of Plasmodium falciparum AMA-1 antigen from the Northeast Indian state of Tripura and comparison with global sequences: implications for vaccine development. Malar J. 2022;21:62.
pubmed: 35193607
pmcid: 8861999
doi: 10.1186/s12936-022-04081-1
Ajibola O, Diop MF, Ghansah A, Amenga-Etego L, Golassa L, Apinjoh T, et al. In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations. Sci Rep. 2021;11:16215.
pubmed: 34376744
pmcid: 8355234
doi: 10.1038/s41598-021-95442-4
Chenet SM, Branch OH, Escalante AA, Lucas CM, Bacon DJ. Genetic diversity of vaccine candidate antigens in Plasmodium falciparum isolates from the Amazon basin of Peru. Malar J. 2008;7:93.
pubmed: 18505558
pmcid: 2432069
doi: 10.1186/1475-2875-7-93
Reeder JC, Wapling J, Mueller I, Siba PM, Barry AE. Population genetic analysis of the Plasmodium falciparum 6-cys protein Pf38 in Papua New Guinea reveals domain-specific balancing selection. Malar J. 2011;10:126.
pubmed: 21569602
pmcid: 3112457
doi: 10.1186/1475-2875-10-126
DHS. Malaria Indicator Survey 2017; 2018. https://dhsprogram.com/pubs/pdf/MIS31/MIS31.pdf . Accessed 15 Jan 2024.