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Pathogenicity and virulence of malaria: Sticky problems and tricky solutions

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Article: 2150456 | Received 05 Jun 2022, Accepted 19 Oct 2022, Published online: 04 Jan 2023

References

  • World Health Organization. Word Malaria Report 2021. 2021. Available from: https://www.who.int/publications/i/item/9789240040496
  • Kojom Foko LP, Arya A, Sharma A, et al. Epidemiology and clinical outcomes of severe Plasmodium vivax malaria in India. J Infect. 2021;82(6):231–34.
  • Grigg MJ, William T, Barber BE, et al. Age-Related Clinical Spectrum of Plasmodium knowlesi Malaria and Predictors of Severity. Clin Infect Dis. 2018;67(3):350–359. DOI:10.1093/cid/ciy065
  • World Health Organization. WHO Guidelines for Malaria. 2021. Available from: https://www.who.int/publications/i/item/guidelines-for-malaria
  • Paton RS, Kamau A, Akech S, et al. Malaria infection and severe disease risks in Africa. Science. 2021;373(6557):926–931. https://doi.org/10.1126/science.abj0089
  • Kamau A, Paton RS, Akech S, et al. Malaria hospitalisation in East Africa: age, phenotype and transmission intensity. BMC Med. 2022;20(1):28. DOI:10.1186/s12916-021-02224-w
  • Kapesa A, Kweka EJ, Atieli H, et al. The current malaria morbidity and mortality in different transmission settings in Western Kenya. PLoS One. 2018;13(8):e0202031. https://doi.org/10.1371/journal.pone.0202031
  • Rogerson SJ, Desai M, Mayor A, et al. Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem. Lancet Infect Dis. 2018;18(4):e107–118. DOI:10.1016/S1473-3099(18)30066-5
  • Tatem AJ, Gething PW, Smith DL, et al. Urbanization and the global malaria recession. Malar J. 2013;12(1):133.
  • Doumbe-Belisse P, Kopya E, Ngadjeu CS, et al. Urban malaria in sub-Saharan Africa: dynamic of the vectorial system and the entomological inoculation rate. Malar J. 2021;20(1):364. DOI:10.1186/s12936-021-03891-z
  • De Silva PM, Marshall JM. Factors contributing to urban malaria transmission in sub-saharan Africa: a systematic review. J Trop Med. 2012;2012:819563.
  • Multini LC, AL da S DS, Marrelli MT, et al. The influence of anthropogenic habitat fragmentation on the genetic structure and diversity of the malaria vector Anopheles cruzii (Diptera: culicidae). Sci Rep. 2020;10(1):18018.
  • Balkew M, Mumba P, Yohannes G, et al. An update on the distribution, bionomics, and insecticide susceptibility of Anopheles stephensi in Ethiopia, 2018–2020. Malar J. 2021;20(1):263. DOI:10.1186/s12936-021-03801-3
  • Antonio-Nkondjio C, Fossog BT, Ndo C, et al. Anopheles gambiae distribution and insecticide resistance in the cities of Douala and Yaoundé (Cameroon): influence of urban agriculture and pollution. Malar J. 2011;10(1):154. DOI:10.1186/1475-2875-10-154
  • Thomas S, Ravishankaran S, Justin NAJA, et al. Resting and feeding preferences of Anopheles stephensi in an urban setting, perennial for malaria. Malar J. 2017;16(1):111. DOI:10.1186/s12936-017-1764-5
  • Sinka ME, Pironon S, Massey NC, et al. A new malaria vector in Africa: predicting the expansion range of Anopheles stephensi and identifying the urban populations at risk. Proc Natl Acad Sci U S A. 2020;117(40):24900–24908. DOI:10.1073/pnas.2003976117
  • Worges M, Whitehurst N, Saye R, et al. Performance Outcomes from Africa-Based Malaria Diagnostic Competency Assessment Courses. Am J Trop Med Hyg. 2019;100(4):851–860. DOI:10.4269/ajtmh.18-0361
  • Kamaliddin C, Sutherland CJ, Houze S, et al. The Role of Ultrasensitive Molecular Methods for Detecting Malaria—The Broader Perspective. Clin Infect Dis. 2021;73(6):e1387–1390. DOI:10.1093/cid/ciab221
  • Britton S, Cheng Q, McCarthy JS. Novel molecular diagnostic tools for malaria elimination: a review of options from the point of view of high-throughput and applicability in resource limited settings. Malar J. 2016;15(1):88.
  • Zelman BW, Baral R, Zarlinda I, et al. Costs and cost-effectiveness of malaria reactive case detection using loop-mediated isothermal amplification compared to microscopy in the low transmission setting of Aceh Province, Indonesia. Malar J. 2018;17(1):220. DOI:10.1186/s12936-018-2361-y
  • Cunningham J, Jones S, Gatton ML, et al. A review of the WHO malaria rapid diagnostic test product testing programme (2008–2018): performance, procurement and policy. Malar J. 2019;18(1):387. DOI:10.1186/s12936-019-3028-z
  • Jejaw Zeleke A, Hailu A, Bayih AG, et al. Plasmodium falciparum histidine-rich protein 2 and 3 genes deletion in global settings (2010–2021): a systematic review and meta-analysis. Malar J. 2022;21(1):26. DOI:10.1186/s12936-022-04051-7
  • Gatton ML, Chaudhry A, Glenn J, et al. Impact of Plasmodium falciparum gene deletions on malaria rapid diagnostic test performance. Malar J. 2020;19(1):392. DOI:10.1186/s12936-020-03460-w
  • Amoah LE, Abankwa J, Oppong A. Plasmodium falciparum histidine rich protein-2 diversity and the implications for PfHRP 2: based malaria rapid diagnostic tests in Ghana. Malar J. 2016;15(1):101.
  • Mihreteab S, Anderson K, Pasay C, et al. Epidemiology of mutant Plasmodium falciparum parasites lacking histidine-rich protein 2/3 genes in Eritrea 2 years after switching from HRP2-based RDTs. Sci Rep. 2021;11(1):21082. DOI:10.1038/s41598-021-00714-8
  • Watson OJ, Slater HC, Verity R, et al. Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa. Elife. 2017;6:e25008. DOI:10.7554/eLife.25008
  • Laveran A. A new parasite found in the blood of malarial patients. Parasitic origin of malarial attacks. Bull Mem Soc Med Hosp Paris. 1880;17:158–164.
  • Mota MM, Hafalla JCR, Rodriguez A. Migration through host cells activates Plasmodium sporozoites for infection. Nat Med. 2002;8(11):1318–1322.
  • Yahata K, Hart MN, Davies H, et al. Gliding motility of Plasmodium merozoites. Proc Natl Acad Sci. 2021;118(48):e2114442118. DOI:10.1073/pnas.2114442118
  • Cowman AF, Berry D, Baum J. The cellular and molecular basis for malaria parasite invasion of the human red blood cell. J Cell Biol. 2012;198(6):961–971.
  • Warncke JD, Beck H-P. Host Cytoskeleton Remodeling throughout the Blood Stages of Plasmodium falciparum. Microbiol Mol Biol Rev. 2019;83(4):e00013–19.
  • Pologe LG, Pavlovec A, Shio H, et al. Primary structure and subcellular localization of the knob-associated histidine-rich protein of Plasmodium falciparum. Proc Natl Acad Sci U S A. 1987;84(20):7139–7143.
  • Jensen AR, Adams Y, Hviid L. Cerebral Plasmodium falciparum malaria: the role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it. Immunol Rev. 2020;293(1):230–252.
  • Francis SE, Sullivan DJ, Goldberg DE. HEMOGLOBIN METABOLISM in the MALARIA PARASITE Plasmodium FALCIPARUM. Annu Rev Microbiol. 1997;51(1):97–123.
  • Beri D, Balan B, Tatu U. Commit, hide and escape: the story of Plasmodium gametocytes. Parasitology. 2018;145(13):1772–1782.
  • Brancucci NMB, Gerdt JP, Wang C, et al. Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum. Cell. 2017;171(7):1532–1544.e15. DOI:10.1016/j.cell.2017.10.020
  • Sinden RE. The cell biology of malaria infection of mosquito: advances and opportunities. Cell Microbiol. 2015;17(4):451–466.
  • Leopold SJ, Watson JA, Jeeyapant A, et al. Investigating causal pathways in severe falciparum malaria: a pooled retrospective analysis of clinical studies. PLoS Med. 2019;16(8):e1002858. DOI:10.1371/journal.pmed.1002858
  • Uyoga S, Wanjiku P, Rop JC, et al. Plasma Plasmodium falciparum Histidine-rich Protein 2 Concentrations in Children with Malaria Infections of Differing Severity in Kilifi, Kenya. Clin Infect Dis. 2021;73(7):e2415–2423. DOI:10.1093/cid/ciaa1141
  • Fox LL, Taylor TE, Pensulo P, et al. Histidine-rich protein 2 plasma levels predict progression to cerebral malaria in Malawian children with Plasmodium falciparum infection. J Infect Dis. 2013;208(3):500–503. DOI:10.1093/infdis/jit176
  • Park GS, Opoka RO, Shabani E, et al. Plasmodium falciparum Histidine-Rich Protein-2 Plasma Concentrations are Higher in Retinopathy-Negative Cerebral Malaria Than in Severe Malarial Anemia. Open Forum Infect Dis. 2017;4(3):ofx151. DOI:10.1093/ofid/ofx151
  • Manning L, Laman M, Stanisic D, et al. Plasma Plasmodium falciparum histidine-rich protein-2 concentrations do not reflect severity of malaria in Papua new Guinean children. Clin Infect Dis. 2011;52(4):440–446. DOI:10.1093/cid/ciq105
  • Silva-Filho JL, Dos-Santos JC, Judice C, et al. Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients. Elife. 2021;10:e71351. DOI:10.7554/eLife.71351
  • Dollat M, Talla C, Sokhna C, et al. Measuring malaria morbidity in an area of seasonal transmission: pyrogenic parasitemia thresholds based on a 20-year follow-up study. PLoS One. 2019;14(6):e0217903. https://doi.org/10.1371/journal.pone.0217903
  • Hartley M-A, Hofmann N, Keitel K, et al. Clinical relevance of low-density Plasmodium falciparum parasitemia in untreated febrile children: a cohort study. PLoS Med. 2020;17(9):e1003318. DOI:10.1371/journal.pmed.1003318
  • Nguyen TN, von Seidlein L, Nguyen TV, et al. The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study. Lancet Infect Dis. 2018;18(5):565–572. DOI:10.1016/S1473-3099(18)30046-X
  • Katrak S, Nayebare P, Rek J, et al. Clinical consequences of submicroscopic malaria parasitaemia in Uganda. Malar J. 2018;17(1):67. DOI:10.1186/s12936-018-2221-9
  • Chen I, Clarke SE, Gosling R, et al. “Asymptomatic” Malaria: a Chronic and Debilitating Infection That Should Be Treated. PLoS Med. 2016;13(1):e1001942. DOI:10.1371/journal.pmed.1001942
  • Slater HC, Ross A, Felger I, et al. The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density. Nat Commun. 2019;10(1):1433. DOI:10.1038/s41467-019-09441-1
  • Rovira-Vallbona E, Moncunill G, Bassat Q, et al. Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case–control study. Malar J. 2012;11(1):181. DOI:10.1186/1475-2875-11-181
  • Kariuki SN, Williams TN. Human genetics and malaria resistance. Hum Genet. 2020;139(6–7):801–811.
  • Goheen MM, Campino S, Cerami C. The role of the red blood cell in host defence against falciparum malaria: an expanding repertoire of evolutionary alterations. Br J Haematol. 2017;179(4):543–556.
  • Band G, Leffler EM, Jallow M, et al. Malaria protection due to sickle haemoglobin depends on parasite genotype. Nature. 2022;602(7895):106–111. https://doi.org/10.1038/s41586-021-04288-3
  • Ndila CM, Uyoga S, Macharia AW, et al. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study. Lancet Haematol. 2018;5(8):e333–345. DOI:10.1016/S2352-3026(18)30107-8
  • Timmann C, Thye T, Vens M, et al. Genome-wide association study indicates two novel resistance loci for severe malaria. Nature. 2012;489(7416):443–446. https://doi.org/10.1038/nature11334
  • Leffler EM, Band G, Busby GBJ, et al. Resistance to malaria through structural variation of red blood cell invasion receptors. Science. 2017;356(6343):eaam6393. DOI:10.1126/science.aam6393
  • Kariuki SN, Marin-Menendez A, Introini V, et al. Red blood cell tension protects against severe malaria in the Dantu blood group. Nature. 2020;585(7826):579–583. https://doi.org/10.1038/s41586-020-2726-6
  • Petersen JEV, Saelens JW, Freedman E, et al. Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes. PLoS Pathog. 2021;17(6):e1009659. DOI:10.1371/journal.ppat.1009659
  • Fairhurst RM, Baruch DI, Brittain NJ, et al. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature. 2005;435(7045):1117–1121. https://doi.org/10.1038/nature03631
  • Nguetse CN, Purington N, Ebel ER, et al. A common polymorphism in the mechanosensitive ion channel PIEZO1 is associated with protection from severe malaria in humans. Proc Natl Acad Sci U S A. 2020;117(16):9074–9081. DOI:10.1073/pnas.1919843117
  • Cholera R, Brittain NJ, Gillrie MR, et al. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc Natl Acad Sci U S A. 2008;105(3):991–996. DOI:10.1073/pnas.0711401105
  • McQuaid F, Rowe JA. Rosetting revisited: a critical look at the evidence for host erythrocyte receptors in Plasmodium falciparum rosetting. Parasitology. 2020;147(1):1–11.
  • Milner DA, Whitten RO, Kamiza S, et al. The systemic pathology of cerebral malaria in African children. Front Cell Infect Microbiol. 2014;4:1–13. DOI:10.3389/fcimb.2014.00104
  • Bachmann A, Esser C, Petter M, et al. Absence of erythrocyte sequestration and lack of multicopy gene family expression in Plasmodium falciparum from a splenectomized malaria patient. PLoS One. 2009;4(10):e7459. https://doi.org/10.1371/journal.pone.0007459
  • Mahamar A, Attaher O, Swihart B, et al. Host factors that modify Plasmodium falciparum adhesion to endothelial receptors. Sci Rep. 2017;7(1):13872. DOI:10.1038/s41598-017-14351-7
  • Langreth SG, Peterson E. Pathogenicity, stability, and immunogenicity of a knobless clone of Plasmodium falciparum in Colombian owl monkeys. Infect Immun. 1985;47(3):760–766.
  • Stanisic DI, Gerrard J, Fink J, et al. Infectivity of Plasmodium falciparum in Malaria-Naive Individuals is Related to Knob Expression and Cytoadherence of the Parasite. Infect Immun. 2016;84(9):2689–2696. DOI:10.1128/IAI.00414-16
  • Webster R, Sekuloski S, Odedra A, et al. Safety, infectivity and immunogenicity of a genetically attenuated blood-stage malaria vaccine. BMC Med. 2021;19(1):293. DOI:10.1186/s12916-021-02150-x
  • Arakawa C, Gunnarsson C, Howard C, et al. Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries. Sci Adv. 2020;6(3):eaay7243. DOI:10.1126/sciadv.aay7243
  • Joice R, Nilsson SK, Montgomery J, et al. Plasmodium falciparum transmission stages accumulate in the human bone marrow. Sci Transl Med. 2014;6(244):244re5. DOI:10.1126/scitranslmed.3008882
  • De Niz M, Meibalan E, Mejia P, et al. Plasmodium gametocytes display homing and vascular transmigration in the host bone marrow. Sci Adv. 2018;4(5):eaat3775. DOI:10.1126/sciadv.aat3775
  • Rogers NJ, Hall BS, Obiero J, et al. A model for sequestration of the transmission stages of Plasmodium falciparum: adhesion of gametocyte-infected erythrocytes to human bone marrow cells. Infect Immun. 2000;68(6):3455–3462. DOI:10.1128/IAI.68.6.3455-3462.2000
  • Silvestrini F, Tibúrcio M, Bertuccini L, et al. Differential Adhesive Properties of Sequestered Asexual and Sexual Stages of Plasmodium falciparum on Human Endothelial Cells are Tissue Independent. PLoS One. 2012;7(2):e31567.
  • Messina V, Valtieri M, Rubio M, et al. Gametocytes of the Malaria Parasite Plasmodium falciparum Interact with and Stimulate Bone Marrow Mesenchymal Cells to Secrete Angiogenetic Factors. Front Cell Infect Microbiol. 2018;8:50. DOI:10.3389/fcimb.2018.00050
  • Camarda G, Jirawatcharadech P, Priestley RS, et al. Antimalarial activity of primaquine operates via a two-step biochemical relay. Nat Commun. 2019;10(1):3226. DOI:10.1038/s41467-019-11239-0
  • Carvalho BO, Lopes SCP, Nogueira PA, et al. On the Cytoadhesion of Plasmodium vivax –Infected Erythrocytes. J Infect Dis. 2010;202(4):638–647. DOI:10.1086/654815
  • Lacerda MVG, Fragoso SCP, Alecrim MGC, et al. Postmortem characterization of patients with clinical diagnosis of Plasmodium vivax malaria: to what extent does this parasite kill? Clin Infect Dis. 2012;55(8):e67–74. DOI:10.1093/cid/cis615
  • Obaldia IN, Meibalan E, JM S, et al. Bone Marrow is a Major Parasite Reservoir in Plasmodium vivax Infection. Infection MBio. 2018;9(3): e00625-18. doi:10.1128/mBio.00625-18.
  • Baro B, Deroost K, Raiol T, et al. Plasmodium vivax gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile. PLoS Negl Trop Dis. 2017;11(4):e0005365. DOI:10.1371/journal.pntd.0005365
  • Kho S, Qotrunnada L, Leonardo L, et al. Hidden Biomass of Intact Malaria Parasites in the Human Spleen. N Engl J Med. 2021;384(21):2067–2069. DOI:10.1056/NEJMc2023884
  • Pongponratn E, Riganti M, Harinasuta T, et al. Electron microscopic study of phagocytosis in human spleen in falciparum malaria. Southeast Asian J Trop Med Public Health. 1989 20(1):31–39.
  • Ho M, Bannister LH, Looareesuwan S, et al. Cytoadherence and ultrastructure of Plasmodium falciparum-infected erythrocytes from a splenectomized patient. Infect Immun. 1992;60(6):2225–2228.
  • Safeukui I, Correas J-M, Brousse V, et al. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen. Blood. 2008;112(6):2520–2528. https://doi.org/10.1182/blood-2008-03-146779
  • Elizalde-Torrent A, Trejo-Soto C, Méndez-Mora L, et al. Pitting of malaria parasites in microfluidic devices mimicking spleen interendothelial slits. Sci Rep. 2021;11(1):22099. DOI:10.1038/s41598-021-01568-w
  • David PH, Hommel M, Miller LH, et al. Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes. Proc Natl Acad Sci U S A. 1983;80(16):5075–5079. DOI:10.1073/pnas.80.16.5075
  • Fernandez-Becerra C, Bernabeu M, Castellanos A, et al. Plasmodium vivax spleen-dependent genes encode antigens associated with cytoadhesion and clinical protection. Proc Natl Acad Sci U S A. 2020;117(23):13056–13065. DOI:10.1073/pnas.1920596117
  • Doumbo OK, Thera MA, Koné AK, et al. High levels of Plasmodium falciparum rosetting in all clinical forms of severe malaria in African children. Am J Trop Med Hyg. 2009;81(6):987–993. DOI:10.4269/ajtmh.2009.09-0406
  • Rowe A, Obeiro J, Newbold CI, et al. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun. 1995;63(6):2323–2326.
  • Carlson J, Helmby H, Hill AV, et al. Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet. 1990;336(8729):1457–1460. DOI:10.1016/0140-6736(90)93174-n
  • Goel S, Palmkvist M, Moll K, et al. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria. Nat Med. 2015;21(4):314–317. DOI:10.1038/nm.3812
  • Jötten AM, Moll K, Wahlgren M, et al. Blood group and size dependent stability of P. falciparum infected red blood cell aggregates in capillaries. Biomicrofluidics. 2020;14(2):24104. https://doi.org/10.1063/1.5125038
  • Hedberg P, Sirel M, Moll K, et al. Red blood cell blood group a antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes. Malar J. 2021;20(1):441. DOI:10.1186/s12936-021-03975-w
  • Stevenson L, Huda P, Jeppesen A, et al. Investigating the function of Fc-specific binding of IgM to Plasmodium falciparum erythrocyte membrane protein 1 mediating erythrocyte rosetting. Cell Microbiol. 2015;17(6):819–831. DOI:10.1111/cmi.12403
  • Stevenson L, Laursen E, Cowan GJ, et al. α2-Macroglobulin Can Crosslink Multiple Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) Molecules and May Facilitate Adhesion of Parasitized Erythrocytes. PLoS Pathog. 2015;11(7):e1005022. DOI:10.1371/journal.ppat.1005022
  • Al-Yaman F, Genton B, Mokela D, et al. Human cerebral malaria: lack of significant association between erythrocyte rosetting and disease severity. Trans R Soc Trop Med Hyg. 1995;89(1):55–58. DOI:10.1016/0035-9203(95)90658-4
  • Degarege A, Gebrezgi MT, Ibanez G, et al. Effect of the ABO blood group on susceptibility to severe malaria: a systematic review and meta-analysis. Blood Rev. 2019;33:53–62. DOI:10.1016/j.blre.2018.07.002
  • Wang CW, Hviid L. Rifins, rosetting, and red blood cells. Trends Parasitol. 2015;31(7):285–286.
  • Moll K, Palmkvist M, Ch’Ng J, et al. Evasion of Immunity to Plasmodium falciparum: rosettes of Blood Group a Impair Recognition of PfEMP1. PLoS One. 2015;10(12):e0145120. https://doi.org/10.1371/journal.pone.0145120
  • Albrecht L, Lopes SCP, da Silva ABIE, et al. Rosettes integrity protects Plasmodium vivax of being phagocytized. Sci Rep. 2020;10(1):16706. DOI:10.1038/s41598-020-73713-w
  • Lee W-C, Russell B, Lee B, et al. Plasmodium falciparum rosetting protects schizonts against artemisinin. EBioMedicine. 2021;73:103680. DOI:10.1016/j.ebiom.2021.103680
  • Lowe BS, Mosobo M, Bull PC. All four species of human malaria parasites form rosettes. Trans R Soc Trop Med Hyg. 1998;92(5):526.
  • Zhang R, Lee W-C, Lau Y-L, et al. Rheopathologic Consequence of Plasmodium vivax Rosette Formation. PLoS Negl Trop Dis. 2016;10(8):e0004912. DOI:10.1371/journal.pntd.0004912
  • Marín-Menéndez A, Bardají A, Martínez-Espinosa FE, et al. Rosetting in Plasmodium vivax: a cytoadhesion phenotype associated with anaemia. PLoS Negl Trop Dis. 2013;7(4):e2155. DOI:10.1371/journal.pntd.0002155
  • Pain A, Ferguson DJ, Kai O, et al. Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes is a common adhesive phenotype and is associated with severe malaria. Proc Natl Acad Sci U S A. 2001;98(4):1805–1810. DOI:10.1073/pnas.98.4.1805
  • Biswas AK, Hafiz A, Banerjee B, et al. Plasmodium falciparum Uses gC1qr/HABP1/p32 as a Receptor to Bind to Vascular Endothelium and for Platelet-Mediated Clumping. PLoS Pathog. 2007;3(9):e130. DOI:10.1371/journal.ppat.0030130
  • Mayor A, Hafiz A, Bassat Q, et al. Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor. PLoS One. 2011;6(4):e19422. https://doi.org/10.1371/journal.pone.0019422
  • Arman M, Raza A, Tempest LJ, et al. Platelet-Mediated Clumping of Plasmodium falciparum–infected Erythrocytes is Associated with High Parasitemia but Not Severe Clinical Manifestations of Malaria in African Children. Am J Trop Med Hyg. 2007;77(5):943–946. DOI:10.4269/ajtmh.2007.77.943
  • Arman M, Rowe JA. Experimental conditions affect the outcome of Plasmodium falciparum platelet-mediated clumping assays. Malar J. 2008;7(1):243.
  • Chan JA, Fowkes FJI, Beeson JG. Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates. Cell Mol Life Sci. 2014;71(19):3633–3657.
  • Nielsen MA, Staalsoe T, Kurtzhals JAL, et al. Plasmodium falciparum Variant Surface Antigen Expression Varies Between Isolates Causing Severe and Nonsevere Malaria and is Modified by Acquired Immunity. J Immunol. 2002;168(7):3444–3450. DOI:10.4049/jimmunol.168.7.3444
  • Warimwe GM, Keane TM, Fegan G, et al. Plasmodium falciparum var gene expression is modified by host immunity. Proc Natl Acad Sci. 2009;106(51):21801–21806. DOI:10.1073/pnas.0907590106
  • Bull PC, Lowe BS, Kortok M, et al. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat Med. 1998;4(3):358–360. DOI:10.1038/nm0398-358
  • Smith JD, Craig AG, Kriek N, et al. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc Natl Acad Sci U S A. 2000;97(4):1766–1771. DOI:10.1073/pnas.040545897
  • Salanti A, Staalsoe T, Lavstsen T, et al. Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol Microbiol. 2003;49(1):179–191. DOI:10.1046/j.1365-2958.2003.03570.x
  • Roberts DJ, Craig AG, Berendt AR, et al. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992;357(6380):689–692. DOI:10.1038/357689a0
  • Bernabeu M, Lopez FJ, Ferrer M, et al. Functional analysis of Plasmodium vivax VIR proteins reveals different subcellular localizations and cytoadherence to the ICAM-1 endothelial receptor. Cell Microbiol. 2012;14(3):386–400. DOI:10.1111/j.1462-5822.2011.01726.x
  • Requena P, Rui E, Padilla N, et al. Plasmodium vivax VIR Proteins are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women. PLoS Negl Trop Dis. 2016;10(10):e0005009. DOI:10.1371/journal.pntd.0005009
  • Rask TS, Hansen DA, Theander TG, et al. Plasmodium falciparum Erythrocyte Membrane Protein 1 Diversity in Seven Genomes – Divide and Conquer. PLoS Comput Biol. 2010;6(9):e1000933. DOI:10.1371/journal.pcbi.1000933
  • Jensen ATR, Theander TG, Nielsen MA, et al. Plasmodium falciparum Associated with Severe Childhood Malaria Preferentially Expresses PfEMP1 Encoded by Group a var Genes. J Exp Med. 2004;199(9):1179–1190. DOI:10.1084/jem.20040274
  • Rottmann M, Muller D, Jensen ATR, et al. Differential Expression of var Gene Groups is Associated with Morbidity Caused by Plasmodium falciparum Infection in Tanzanian Children. Infect Immun. 2006;74(7):3904–3911. DOI:10.1128/iai.02073-05
  • Bertin GI, Alao MJ, Ndam NT, et al. Expression of the Domain Cassette 8 Plasmodium falciparum Erythrocyte Membrane Protein 1 is Associated with Cerebral Malaria in Benin. PLoS One. 2013;8(7):e68368. DOI:10.1371/journal.pone.0068368
  • Kyriacou HM, Doumbo OK, Challis RJ, et al. Differential var gene transcription in Plasmodium falciparum isolates from patients with cerebral malaria compared to hyperparasitaemia. Mol Biochem Parasitol. 2006;150(2):211–218. DOI:10.1016/j.molbiopara.2006.08.005
  • Jespersen JS, Wang CW, Mkumbaye SI, et al. Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains. EMBO Mol Med. 2016;8(8):839–850. DOI:10.15252/emmm.201606188
  • Lennartz F, Adams Y, Bengtsson A, et al. Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that is Associated with Cerebral Malaria. Cell Host Microbe. 2017;21(3):403–414. DOI:10.1016/j.chom.2017.02.009
  • Kaestli M, Cockburn IA, Cortés A, et al. Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study. J Infect Dis. 2006;193(11):1567–1574. DOI:10.1086/503776
  • AV O, Morrison R, Amos E, et al. A Plasma Survey Using 38 PfEMP1 Domains Reveals Frequent Recognition of the Plasmodium falciparum Antigen VAR2CSA among Young Tanzanian Children. PLoS One. 2012;7(1):e31011. DOI:10.1371/journal.pone.0031011
  • Smith JD, Subramanian G, Gamain B, et al. Classification of adhesive domains in the Plasmodium falciparum Erythrocyte Membrane Protein 1 family. Mol Biochem Parasitol. 2000;110(2):293–310. DOI:10.1016/S0166-6851(00)00279-6
  • Janes JH, Wang CP, Levin-Edens E, et al. Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. PLoS Pathog. 2011;7(5):e1002032. DOI:10.1371/journal.ppat.1002032
  • Robinson BA, Welch TL, Smith JD. Widespread functional specialization of Plasmodium falciparum erythrocyte membrane protein 1 family members to bind CD36 analysed across a parasite genome. Mol Microbiol. 2003;47(5):1265–1278.
  • Mkumbaye SI, Wang CW, Lyimo E, et al. The severity of Plasmodium falciparum infection is associated with transcript levels of var genes encoding endothelial protein C receptor-binding P. falciparum erythrocyte membrane protein 1. Infect Immun. 2017;85(4):1–14. DOI:10.1128/IAI.00841-16
  • Rogerson SJ, Plitt S, Taylor TE, et al. Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria. Am J Trop Med Hyg. 1999;61(3):467–472. DOI:10.4269/ajtmh.1999.61.467
  • Tuikue Ndam N, Moussiliou A, Lavstsen T, et al. Parasites Causing Cerebral Falciparum Malaria Bind Multiple Endothelial Receptors and Express EPCR and ICAM-1-Binding PfEMP1. J Infect Dis. 2017;215(12):1918–1925. DOI:10.1093/infdis/jix230
  • Wichers JS, Tonkin-Hill G, Thye T, et al. Common virulence gene expression in adult first-time infected malaria patients and severe cases. Elife. 2021;10:e69040. DOI:10.7554/eLife.69040
  • Turner GDH, Morrison H, Jones M, et al. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994;145(5):1057–1069.
  • Avril M, Bernabeu M, Benjamin M, et al. Interaction between endothelial protein C receptor and intercellular adhesion molecule 1 to mediate binding of Plasmodium falciparum-infected erythrocytes to endothelial cells. MBio. 2016;7(4):1–10. https://doi.org/10.1128/mBio.00615-16
  • Wassmer SC, Lépolard C, Traoré B, et al. Platelets Reorient Plasmodium falciparum –Infected Erythrocyte Cytoadhesion to Activated Endothelial Cells. J Infect Dis. 2004;189(2):180–189. DOI:10.1086/380761
  • Turner L, Lavstsen T, Berger SS, et al. Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature. 2013;498(7455):502–505. https://doi.org/10.1038/nature12216
  • Avril M, Tripathi AK, Brazier AJ, et al. A restricted subset of var genes mediates adherence of Plasmodium falciparum-infected erythrocytes to brain endothelial cells. Proc Natl Acad Sci. 2012;109(26):e1782–90. DOI:10.1073/pnas.1120534109
  • Joste V, Guillochon E, Fraering J, et al. PfEMP1 A-Type ICAM-1-Binding Domains are Not Associated with Cerebral Malaria in Beninese Children. MBio. 2020;11(6):e02103–20. https://doi.org/10.1128/mBio.02103-20
  • Kessler A, Dankwa S, Bernabeu M, et al. Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria. Cell Host Microbe. 2017;22(5):601–614.e5. DOI:10.1016/j.chom.2017.09.009
  • Storm J, Jespersen JS, Seydel KB, et al. Cerebral malaria is associated with differential cytoadherence to brain endothelial cells. EMBO Mol Med. 2019;11(2):1–15. DOI:10.15252/emmm.201809164
  • Shabani E, Hanisch B, Opoka RO, et al. Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria. BMC Med. 2017;15(1):183. DOI:10.1186/s12916-017-0945-y
  • Lavstsen T, Gilbert MTP, Willerslev E, et al. Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children. Proc Natl Acad Sci. 2012;109(26):e1791–1800. DOI:10.1073/pnas.1120455109
  • Bengtsson A, Joergensen L, Rask TS, et al. A Novel Domain Cassette Identifies Plasmodium falciparum PfEMP1 Proteins Binding ICAM-1 and is a Target of Cross-Reactive, Adhesion-Inhibitory Antibodies. J Immunol. 2013;190(1):240–249. DOI:10.4049/jimmunol.1202578
  • Olsen RW, Ecklu-Mensah G, Bengtsson A, et al. Natural and Vaccine-Induced Acquisition of Cross-Reactive IgG-Inhibiting ICAM-1-Specific Binding of a Plasmodium falciparum PfEMP1 Subtype Associated Specifically with Cerebral Malaria. Infect Immun. 2018;86(4):1–17. DOI:10.1128/IAI.00622-17
  • Tonkin-Hill GQ, Trianty L, Noviyanti R, et al. The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen–encoding var genes. PLoS Biol. 2018;16(3):e2004328. DOI:10.1371/journal.pbio.2004328
  • Duffy MF, Caragounis A, Noviyanti R, et al. Transcribed var Genes Associated with Placental Malaria in Malawian Women. Infect Immun. 2006;74(8):4875–4883. DOI:10.1128/IAI.01978-05
  • Tuikue Ndam NG, Salanti A, Bertin G, et al. High Level of var2csa Transcription by Plasmodium falciparum Isolated from the Placenta. J Infect Dis. 2005;192(2):331–335. DOI:10.1086/430933
  • Clausen TM, Christoffersen S, Dahlbäck M, et al. Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate a in placental malaria. J Biol Chem. 2012;287(28):23332–23345. DOI:10.1074/jbc.M112.348839
  • Doolan DL, Dobaño C, Baird JK. Acquired immunity to malaria. Clin Microbiol Rev. 2009;22(1):13–36.
  • Griffin JT, Déirdre Hollingsworth T, Reyburn H, et al. Gradual acquisition of immunity to severe malaria with increasing exposure. Proc R Soc B Biol Sci. 2015;282(1801):20142657. DOI:10.1098/rspb.2014.2657
  • Gupta S, Snow RW, Donnelly CA, et al. Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med. 1999;5(3):340–343. DOI:10.1038/6560
  • Fowkes FJI, Boeuf P, Bees JG. Immunity to malaria in an era of declining malaria transmission. Parasitology. 2016;143(2):139–153.
  • Cohen S, McGregor IA, Carrington S. Gamma-globulin and acquired immunity to human malaria. Nature. 1961;192(4804):733–737.
  • Kanoi BN, Nagaoka H, Morita M, et al. Comprehensive analysis of antibody responses to Plasmodium falciparum erythrocyte membrane protein 1 domains. Vaccine. 2018;36(45):6826–6833. https://doi.org/10.1016/j.vaccine.2018.08.058
  • Smith TG, Serghides L, Patel SN, et al. CD36-mediated nonopsonic phagocytosis of erythrocytes infected with stage I and IIA gametocytes of Plasmodium falciparum. Infect Immun. 2003;71(1):393–400. DOI:10.1128/IAI.71.1.393-400.2003
  • Saeed M, Roeffen W, Alexander N, et al. Plasmodium falciparum Antigens on the Surface of the Gametocyte-Infected Erythrocyte. PLoS One. 2008;3(5):e2280. DOI:10.1371/journal.pone.0002280
  • Chan JA, Drew DR, Reiling L, et al. Low levels of human antibodies to gametocyte-infected erythrocytes contrasts the PfEMP1-dominant response to asexual stages in P. falciparum malaria. Front Immunol. 2019;10:1–8. DOI:10.3389/fimmu.2018.03126
  • Drakeley CJ, Bousema JT, Akim NIJ, et al. Transmission-reducing immunity is inversely related to age in Plasmodium falciparum gametocyte carriers. Parasite Immunol. 2006;28(5):185–190. DOI:10.1111/j.1365-3024.2005.00818.x
  • Stone WJR, Campo JJ, Ouédraogo AL, et al. Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity. Nat Commun. 2018;9(1):558. DOI:10.1038/s41467-017-02646-2
  • Mendis KN, Munesinghe YD, de Silva YN, et al. Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans. Infect Immun. 1987;55(2):369–372. DOI:10.1128/iai.55.2.369-372.1987
  • Acquah FK, Adjah J, Williamson KC, et al. Transmission-Blocking Vaccines: old Friends and New Prospects. Infect Immun. 2019;87(6). e00775-18. DOI:10.1128/IAI.00775-18.
  • RM DJ, Meerstein-Kessel L, Da DF, et al. Monoclonal antibodies block transmission of genetically diverse Plasmodium falciparum strains to mosquitoes. NPJ Vaccines. 2021;6(1):101. DOI:10.1038/s41541-021-00366-9
  • Cockburn IA, Seder RA. Malaria prevention: from immunological concepts to effective vaccines and protective antibodies. Nat Immunol. 2018;19(11):1199–1211.
  • Ishizuka AS, Lyke KE, DeZure A, et al. Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nat Med. 2016;22(6):614–623. DOI:10.1038/nm.4110
  • Cockburn IA, Amino R, Kelemen RK, et al. In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages. Proc Natl Acad Sci U S A. 2013;110(22):9090–9095. DOI:10.1073/pnas.1303858110
  • Feng G, Wines BD, Kurtovic L, et al. Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites. Nat Commun. 2021;12(1):1742. DOI:10.1038/s41467-021-21998-4
  • Bousema T, Barry A, Behet MC, et al. Functional antibodies against Plasmodium falciparum sporozoites are associated with a longer time to qPCR-detected infection among schoolchildren in Burkina Faso. Wellcome Open Res. 2019;3:1–40. DOI:10.12688/wellcomeopenres.14932.2
  • Mishra S, Nussenzweig RS, Nussenzweig V. Antibodies to Plasmodium circumsporozoite protein (CSP) inhibit sporozoite’s cell traversal activity. J Immunol Methods. 2012;377(1–2):47–52.
  • Longley JR, Reyes-Sandoval A, Eduardo M-D, et al. Acquisition and Longevity of Antibodies to Plasmodium vivax Preerythrocytic Antigens in Western Thailand. Clin Vaccine Immunol. 2016;23(2):117–124. DOI:10.1128/CVI.00501-15
  • Daou M, Kouriba B, Ouédraogo N, et al. Protection of Malian children from clinical malaria is associated with recognition of multiple antigens. Malar J. 2015;14(1):56. DOI:10.1186/s12936-015-0567-9
  • Crompton PD, Kayala MA, Traore B, et al. A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci U S A. 2010;107(15):6958–6963. DOI:10.1073/pnas.1001323107
  • Offeddu V, Olotu A, Osier F, et al. High Sporozoite Antibody Titers in Conjunction with Microscopically Detectable Blood Infection Display Signatures of Protection from Clinical Malaria. Front Immunol. 2017;8:488. DOI:10.3389/fimmu.2017.00488
  • Adepoju P. RTS,S malaria vaccine pilots in three African countries. Lancet. 2019;393(10182):1685.
  • Kurtovic L, Atre T, Feng G, et al. Multifunctional Antibodies are Induced by the RTS,S Malaria Vaccine and Associated with Protection in a Phase 1/2a Trial. J Infect Dis. 2021;224(7):1128–1138. DOI:10.1093/infdis/jiaa144
  • RTS, S Clinical Trials Partnership GBS. 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(9988):31–45. doi: 10.1016/S0140-6736(15)60721-8.
  • Moon JE, Greenleaf ME, Regules JA, et al. A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01(E) in a controlled human malaria infection challenge. Vaccine. 2021;39(43):6398–6406. DOI:10.1016/j.vaccine.2021.09.024
  • Datoo MS, Natama MH, Somé A, 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(10287):1809–1818. DOI:10.1016/S0140-6736(21)00943-0
  • Chandramohan D, Zongo I, Sagara I, et al. Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention. N Engl J Med. 2021;385(11):1005–1017. DOI:10.1056/nejmoa2026330
  • Jongo SA, Urbano V, Church LWP, et al. Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults. Am J Trop Med Hyg. 2021;104(1):283–293. DOI:10.4269/ajtmh.20-0435
  • Walk J, Reuling IJ, Behet MC, et al. Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial. BMC Med. 2017;15(1):168. DOI:10.1186/s12916-017-0923-4
  • Sulyok Z, Fendel R, Eder B, et al. Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial. Nat Commun. 2021;12(1):2518. DOI:10.1038/s41467-021-22740-w
  • Murphy SC, Deye GA, Sim BKL, et al. PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: a randomized, placebo-controlled trial with controlled human malaria infection. PLoS Pathog. 2021;17(5):e1009594. DOI:10.1371/journal.ppat.1009594
  • Oneko M, Steinhardt LC, Yego R, et al. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial. Nat Med. 2021;27(9):1636–1645. DOI:10.1038/s41591-021-01470-y
  • Bucşan AN, Williamson KC. Setting the stage: the initial immune response to blood-stage parasites. Virulence. 2020;11(1):88–103.
  • Rathnayake D, Aitken EH, Rogerson SJ. Beyond Binding: the Outcomes of Antibody-Dependent Complement Activation in Human Malaria. Front Immunol. 2021;12:683404.
  • Paul G, Deshmukh A, Kumar Chourasia B, et al. Protein–protein interaction studies reveal the Plasmodium falciparum merozoite surface protein-1 region involved in a complex formation that binds to human erythrocytes. Biochem J. 2018;475(6):1197–1209. DOI:10.1042/BCJ20180017
  • Chen L, Xu Y, Wong W, et al. Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA. Elife. 2017;6:e21347. DOI:10.7554/eLife.21347
  • Feng G, Boyle MJ, Cross N, et al. Human Immunization with a Polymorphic Malaria Vaccine Candidate Induced Antibodies to Conserved Epitopes That Promote Functional Antibodies to Multiple Parasite Strains. J Infect Dis. 2018;218(1):35–43. DOI:10.1093/infdis/jiy170
  • Garcia-Senosiain A, Kana IH, Singh S, et al. Neutrophils dominate in opsonic phagocytosis of P. falciparum blood-stage merozoites and protect against febrile malaria. Commun Biol. 2021;4:984. DOI:10.1038/s42003-021-02511-5
  • Boyle MJ, Reiling L, Feng G, et al. Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria. Immunity. 2015;42(3):580–590. https://doi.org/10.1016/j.immuni.2015.02.012
  • Cowman AF, Crabb BS. Invasion of red blood cells by malaria parasites. Cell. 2006;124(4):755–766.
  • Aniweh Y, Nyarko PB, Charles-Chess E, et al. Plasmodium falciparum Merozoite Associated Armadillo Protein (PfMAAP) is Apically Localized in Free Merozoites and Antibodies are Associated with Reduced Risk of Malaria. Front Immunol. 2020;11:505. DOI:10.3389/fimmu.2020.00505
  • Michelow IC, Park S, Tsai S-W, et al. A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies. J Exp Med. 2021;218(9):e20200170. DOI:10.1084/jem.20200170
  • Hamre KES, Ondigo BN, Hodges JS, et al. Antibody Correlates of Protection from Clinical Plasmodium falciparum Malaria in an Area of Low and Unstable Malaria Transmission. Am J Trop Med Hyg. 2020;103(6):2174–2182. DOI:10.4269/ajtmh.18-0805
  • Sakamoto H, Takeo S, Takashima E, et al. Identification of target proteins of clinical immunity to Plasmodium falciparum in a region of low malaria transmission. Parasitol Int. 2018;67(2):203–208. DOI:10.1016/j.parint.2017.12.002
  • Weaver R, Reiling L, Feng G, et al. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. Sci Rep. 2016;6(1):1–10. DOI:10.1038/srep33094
  • Richards JS, Stanisic DI, Fowkes FJI, et al. Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia. Clin Infect Dis. 2010;51(8):e50–60. DOI:10.1086/656413
  • Kana IH, Garcia-Senosiain A, Singh SK, et al. Cytophilic Antibodies Against Key Plasmodium falciparum Blood Stage Antigens Contribute to Protection Against Clinical Malaria in a High Transmission Region of Eastern India. J Infect Dis. 2018;218(6):956–965. DOI:10.1093/infdis/jiy258
  • Kana IH, Singh SK, Garcia-Senosiain A, et al. Breadth of Functional Antibodies is Associated with Plasmodium falciparum Merozoite Phagocytosis and Protection Against Febrile Malaria. J Infect Dis. 2019;220(2):275–284. DOI:10.1093/infdis/jiz088
  • Duncan CJA, Sheehy SH, Ewer KJ, et al. Impact on malaria parasite multiplication rates in infected volunteers of the protein-in-adjuvant vaccine AMA1-C1/Alhydrogel+CPG 7909. PLoS One. 2011;6(7):e22271. DOI:10.1371/journal.pone.0022271
  • Minassian AM, Silk SE, Barrett JR, et al. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med. 2021;2(6):701–719.e19. https://doi.org/10.1016/j.medj.2021.03.014
  • Dassah S, Adu B, Sirima SB, et al. Extended follow-up of children in a phase 2b trial of the GMZ2 malaria vaccine. Vaccine. 2021;39(31):4314–4319. https://doi.org/10.1016/j.vaccine.2021.06.024
  • Nash SD, Prevots DR, Kabyemela E, et al. A Malaria-Resistant Phenotype with Immunological Correlates in a Tanzanian Birth Cohort Exposed to Intense Malaria Transmission. Am J Trop Med Hyg. 2017;96(5):1190–1196. DOI:10.4269/ajtmh.16-0554
  • Chan JA, Stanisic DI, Duffy MF, et al. Patterns of protective associations differ for antibodies to P. falciparum-infected erythrocytes and merozoites in immunity against malaria in children. Eur J Immunol. 2017;47(12):2124–2136. DOI:10.1002/eji.201747032
  • McCallum FJ, Persson KEM, Fowkes FJI, et al. Differing rates of antibody acquisition to merozoite antigens in malaria: implications for immunity and surveillance. J Leukoc Biol. 2017;101(4):913–925. DOI:10.1189/jlb.5MA0716-294R
  • Adamou R, Dechavanne C, Sadissou I, et al. Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort. Malar J. 2019;18(1):194. DOI:10.1186/s12936-019-2831-x
  • Yman V, Tuju J, White MT, et al. Distinct kinetics of antibodies to 111 Plasmodium falciparum proteins identifies markers of recent malaria exposure. Nat Commun. 2022;13(1):331. DOI:10.1038/s41467-021-27863-8
  • Helb DA, Tetteh KKA, Felgner PL, et al. Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities. Proc Natl Acad Sci. 2015;112(32):e4438–47. DOI:10.1073/pnas.1501705112
  • CV P, Alves JRS, Lima BAS, et al. Blood-stage Plasmodium vivax antibody dynamics in a low transmission setting: a nine year follow-up study in the Amazon region. PLoS One. 2018;13(11):e0207244. DOI:10.1371/journal.pone.0207244
  • Longley RJ, White MT, Takashima E, et al. Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nat Med. 2020;26(5):741–749. DOI:10.1038/s41591-020-0841-4
  • Tayipto Y, Liu Z, Mueller I, et al. Serology for Plasmodium vivax surveillance: a novel approach to accelerate towards elimination. Parasitol Int. 2022;87:102492.
  • Fraser M, Jing W, Bröer S, et al. Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells. PLoS Pathog. 2021;17(2):e1009259. DOI:10.1371/journal.ppat.1009259
  • Giribaldi G, Ulliers D, Mannu F, et al. Growth of Plasmodium falciparum induces stage-dependent haemichrome formation, oxidative aggregation of band 3, membrane deposition of complement and antibodies, and phagocytosis of parasitized erythrocytes. Br J Haematol. 2001;113(2):492–499. DOI:10.1046/j.1365-2141.2001.02707.x
  • Zelter T, Strahilevitz J, Simantov K, et al. Neutrophils impose strong immune pressure against PfEMP1 variants implicated in cerebral malaria. EMBO Rep. 2022:e53641. DOI:10.15252/embr.202153641
  • Gowda NM, Wu X, Kumar S, et al. CD36 Contributes to Malaria Parasite-Induced Pro-Inflammatory Cytokine Production and NK and T Cell Activation by Dendritic Cells. PLoS One. 2013;8(10):e77604. DOI:10.1371/journal.pone.0077604
  • Mavoungou E, Luty AJF, Kremsner PG Natural killer (NK) cell-mediated cytolysis of Plasmodium falciparum-infected human red blood cells in vitro. Eur Cytokine Netw. 2003 14(3):134–142.
  • Baratin M, Roetynck S, Pouvelle B, et al. Dissection of the role of PfEMP1 and ICAM-1 in the sensing of Plasmodium-falciparum-infected erythrocytes by natural killer cells. PLoS One. 2007;2(2):e228. DOI:10.1371/journal.pone.0000228
  • D’Ombrain MC, Voss TS, Maier AG, et al. Plasmodium falciparum Erythrocyte Membrane Protein-1 Specifically Suppresses Early Production of Host Interferon-γ. Cell Host Microbe. 2007;2(2):130–138. DOI:10.1016/j.chom.2007.06.012
  • Saito F, Hirayasu K, Satoh T, et al. Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors. Nature. 2017;552(7683):101–105. https://doi.org/10.1038/nature24994
  • Chan J-A, Howell KB, Reiling L, et al. Targets of antibodies against Plasmodium falciparum–infected erythrocytes in malaria immunity. J Clin Invest. 2012;122(9):3227–3238. DOI:10.1172/JCI62182
  • Kanoi BN, Nagaoka H, White MT, et al. Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population. Front Immunol. 2020;11:893. DOI:10.3389/fimmu.2020.00893
  • Travassos MA, Niangaly A, Bailey JA, et al. Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets. Sci Rep. 2018;8(1):6281. DOI:10.1038/s41598-018-24462-4
  • Nilsson Bark SK, Ahmad R, Dantzler K, et al. Quantitative Proteomic Profiling Reveals Novel Plasmodium falciparum Surface Antigens and Possible Vaccine Candidates. Mol Cell Proteomics. 2018;17(1):43–60. DOI:10.1074/mcp.RA117.000076
  • Aitken EH, Damelang T, Ortega-Pajares A, et al. Developing a multivariate prediction model of antibody features associated with protection of malaria-infected pregnant women from placental malaria. Elife. 2021;10:1–30. DOI:10.7554/eLife.65776
  • Arora G, Hart GT, Manzella-Lapeira J, et al. NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. Elife. 2018;7:1–20. DOI:10.7554/eLife.36806
  • Chan J-A, Boyle MJ, Moore KA, et al. Antibody Targets on the Surface of Plasmodium falciparum– Infected Erythrocytes That are Associated with Immunity to Severe Malaria in Young Children. J Infect Dis. 2019;219(5):819–828. DOI:10.1093/infdis/jiy580
  • Aitken EH, Mahanty S, Rogerson SJ. Antibody effector functions in malaria and other parasitic diseases: a few needles and many haystacks. Immunol Cell Biol. 2020;98(4):264–275.
  • Akhouri RR, Goel S, Furusho H, et al. Architecture of Human IgM in Complex with P. falciparum Erythrocyte Membrane Protein 1. Cell Rep. 2016;14(4):723–736. DOI:10.1016/j.celrep.2015.12.067
  • Goodyer ID, Pouvelle B, Schneider TG, et al. Characterization of macromolecular transport pathways in malaria-infected erythrocytes. Mol Biochem Parasitol. 1997;87(1):13–28. https://doi.org/10.1016/S0166-6851(97)00039-X
  • Kurtis JD, Raj DK, Michelow IC, et al. Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants from Severe Malaria. Clin Infect Dis. 2019;68(10):1718–1724. DOI:10.1093/cid/ciy728
  • Raj DK, Nixon CP, Nixon CE, et al. Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection. Science. 2014;344(6186):871–877. https://doi.org/10.1126/science.1254417
  • Perrin AJ, Bisson C, Faull PA, et al. Malaria Parasite Schizont Egress Antigen-1 Plays an Essential Role in Nuclear Segregation during Schizogony. MBio. 2021;12(2): e03377-20. https://doi.org/10.1128/mBio.03377-20.
  • Larsen MD, Del Pilar Quintana M, Ditlev SB, et al. Evasion of classical complement pathway activation on Plasmodium falciparum-infected erythrocytes opsonized by PfEMP1-Specific IgG. Front Immunol. 2019;10:1–10. DOI:10.3389/fimmu.2018.03088
  • Azasi Y, Low LM, Just AN, et al. Complement C1s cleaves PfEMP1 at interdomain conserved sites inhibiting Plasmodium falciparum cytoadherence. Proc Natl Acad Sci U S A. 2021;118(22):1–10. DOI:10.1073/pnas.2104166118
  • Gonçalves BP, Huang CY, Morrison R, et al. Parasite burden and severity of malaria in Tanzanian children. N Engl J Med. 2014;370(19):1799–1808. DOI:10.1056/NEJMoa1303944
  • Obeng-Adjei N, Larremore DB, Turner L, et al. Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection. JCI Insight. 2020;5(12):e137262. https://doi.org/10.1172/jci.insight.137262
  • Cham GKK, Turner L, Lusingu J, et al. Sequential, Ordered Acquisition of Antibodies to Plasmodium falciparum Erythrocyte Membrane Protein 1 Domains. J Immunol. 2009;183(5):3356–3363. DOI:10.4049/jimmunol.0901331
  • Bachmann A, Bruske E, Krumkamp R, et al. Controlled human malaria infection with Plasmodium falciparum demonstrates impact of naturally acquired immunity on virulence gene expression. PLoS Pathog. 2019;15(7):e1007906. DOI:10.1371/journal.ppat.1007906
  • Ricke CH, Staalsoe T, Koram K, et al. Plasma Antibodies from Malaria-Exposed Pregnant Women Recognize Variant Surface Antigens on Plasmodium falciparum -Infected Erythrocytes in a Parity-Dependent Manner and Block Parasite Adhesion to Chondroitin Sulfate a. J Immunol. 2000;165(6):3309–3316. DOI:10.4049/jimmunol.165.6.3309
  • Cutts JC, Agius PA, Lin Z, et al. Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review. BMC Med. 2020;18(1):1–21. DOI:10.1186/s12916-019-1467-6
  • Larsen MD, Lopez-Perez M, Dickson EK, et al. Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination. Nat Commun. 2021;12(1):5838. DOI:10.1038/s41467-021-26118-w
  • Mayor A, Kumar U, Bardají A, et al. Improved pregnancy outcomes in women exposed to malaria with high antibody levels against Plasmodium falciparum. J Infect Dis. 2013;207(11):1664–1674. DOI:10.1093/infdis/jit083
  • Staalsoe T, Shulman CE, Bulmer JN, et al. Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria. Lancet. 2004;363(9405):283–289. DOI:10.1016/S0140-6736(03)15386-X
  • Duffy PE, Fried M. Antibodies that inhibit Plasmodium falciparum adhesion to chondroitin sulfate a are associated with increased birth weight and the gestational age of newborns. Infect Immun. 2003;71(11):6620–6623.
  • Teo A, Hasang W, Randall LM, et al. Decreasing malaria prevalence and its potential consequences for immunity in pregnant women. J Infect Dis. 2014;210(9):1444–1455. DOI:10.1093/infdis/jiu264
  • Fried M, Kurtis JD, Swihart B, et al. Antibody levels to recombinant VAR2CSA domains vary with Plasmodium falciparum parasitaemia, gestational age, and gravidity, but do not predict pregnancy outcomes. Malar J. 2018;17(1):106. DOI:10.1186/s12936-018-2258-9
  • Sirima SB, Richert L, Chêne A, et al. PRIMVAC vaccine adjuvanted with Alhydrogel or GLA-SE to prevent placental malaria: a first-in-human, randomised, double-blind, placebo-controlled study. Lancet Infect Dis. 2020;20(5):585–597. DOI:10.1016/S1473-3099(19)30739-X
  • Mordmüller B, Sulyok M, Egger-Adam D, et al. First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, a Vaccine Candidate to Prevent Pregnancy-associated Malaria. Clin Infect Dis. 2019;69(9):1509–1516. DOI:10.1093/cid/ciy1140
  • Doritchamou JYA, Renn JP, Jenkins B, et al. A single full-length VAR2CSA ectodomain variant purifies broadly neutralizing antibodies against placental malaria isolates. Elife. 2022;11:e76264. DOI:10.7554/eLife.76264
  • Tessema SK, Nakajima R, Jasinskas A, et al. Protective Immunity against Severe Malaria in Children is Associated with a Limited Repertoire of Antibodies to Conserved PfEMP1 Variants. Cell Host & Microbe. 2019;26(5):579–590.e5. https://doi.org/10.1016/j.chom.2019.10.012
  • Rambhatla JS, Davis TME, Warrel J, et al. Acquisition of Antibodies Against Endothelial Protein C Receptor–Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria. J Infect Dis. 2019;219(5):808–818. DOI:10.1093/infdis/jiy564
  • Rambhatla JS, Tonkin-Hill GQ, Takashima E, et al. Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains. Infect Immun. 2022;90(2):e0043521. DOI:10.1128/iai.00435-21
  • Tessema SK, Utama D, Chesnokov O, et al. Antibodies to Intercellular Adhesion Molecule 1-Binding Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLβ are Biomarkers of Protective Immunity to Malaria in a Cohort of Young Children from Papua New Guinea. Infect Immun. 2018;86(8):1–14. DOI:10.1128/iai.00485-17
  • Araj BN, Swihart B, Morrison R, et al. Antibody Levels to Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLγ11 and DBLδ-1 Predict Reduction in Parasite Density. mSystems. 2021;6(3):1–10. DOI:10.1128/mSystems.00347-21
  • Angeletti D, Albrecht L, Wahlgren M, et al. Analysis of antibody induction upon immunization with distinct NTS-DBL1α-domains of PfEMP1 from rosetting Plasmodium falciparum parasites. Malar J. 2013;12(1):32.
  • Albrecht L, Angeletti D, Moll K, et al. B-cell epitopes in NTS-DBL1α of PfEMP1 recognized by human antibodies in rosetting Plasmodium falciparum. PLoS One. 2014;9(12):e113248. https://doi.org/10.1371/journal.pone.0113248
  • Kessler A, Campo JJ, Harawa V, et al. Convalescent Plasmodium falciparum-specific seroreactivity does not correlate with paediatric malaria severity or Plasmodium antigen exposure. Malar J. 2018;17(1):178. DOI:10.1186/s12936-018-2323-4
  • Badaut C, Visitdesotrakul P, Chabry A, et al. Author Correction: IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria. Sci Rep. 2021;11(1):1–12. DOI:10.1038/s41598-021-82444-5
  • Lusingu JPA, Jensen ATR, Vestergaard LS, et al. Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. Infect Immun. 2006;74(5):2867–2875. DOI:10.1128/IAI.74.5.2867-2875.2006
  • Ghumra A, Khunrae P, Ataide R, et al. Immunisation with recombinant PfEMP1 domains elicits functional rosette-inhibiting and phagocytosis-inducing antibodies to Plasmodium falciparum. PLoS One. 2011;6(1):e16414. https://doi.org/10.1371/journal.pone.0016414
  • Quintana MDP, Angeletti D, Moll K, et al. Phagocytosis-inducing antibodies to Plasmodium falciparum upon immunization with a recombinant PfEMP1 NTS-DBL1α domain. Malar J. 2016;15(1):1–9. DOI:10.1186/s12936-016-1459-3
  • He X, Xia L, Tumas KC, et al. Type I Interferons and Malaria: a Double-Edge Sword Against a Complex Parasitic Disease. Front Cell Infect Microbiol. 2020;10:594621. DOI:10.3389/fcimb.2020.594621
  • Du Y, Hertoghs N, Duffy FJ, et al. Systems analysis of immune responses to attenuated P. falciparum malaria sporozoite vaccination reveals excessive inflammatory signatures correlating with impaired immunity. PLoS Pathog. 2022;18:e1010282.
  • Dunst J, Kamena F, Matuschewski K. Cytokines and Chemokines in Cerebral Malaria Pathogenesis. Front Cell Infect Microbiol. 2017;7:324.
  • Walk J, Keramati F, de Bree LCJ, et al. Controlled Human Malaria Infection Induces Long-Term Functional Changes in Monocytes. Front Mol Biosci. 2020;7:604553. DOI:10.3389/fmolb.2020.604553
  • Mandala WL, Msefula CL, Gondwe EN, et al. Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria. Clin Vaccine Immunol. 2017;24(4): e00533-16. doi:10.1128/CVI.00533-16.
  • Royo J, Rahabi M, Kamaliddin C, et al. Changes in monocyte subsets are associated with clinical outcomes in severe malarial anaemia and cerebral malaria. Sci Rep. 2019;9(1):17545. DOI:10.1038/s41598-019-52579-7
  • Achieng AO, Guyah B, Cheng Q, et al. Molecular basis of reduced LAIR1 expression in childhood severe malarial anaemia: implications for leukocyte inhibitory signalling. EBioMedicine. 2019;45:278–289. DOI:10.1016/j.ebiom.2019.06.040
  • Leão L, Puty B, Dolabela MF, et al. Association of cerebral malaria and TNF-α levels: a systematic review. BMC Infect Dis. 2020;20:442. DOI:10.1186/s12879-020-05107-2
  • Raacke M, Kerr A, Dörpinghaus M, et al. Altered Cytokine Response of Human Brain Endothelial Cells after Stimulation with Malaria Patient Plasma. Cells. 2021;10(7):1656. https://doi.org/10.3390/cells10071656
  • Avril M, Benjamin M, Dols M-M, et al. Interplay of Plasmodium falciparum and thrombin in brain endothelial barrier disruption. Sci Rep. 2019;9(1):13142.
  • Harawa V, Njie M, Kessler A, et al. Brain swelling is independent of peripheral plasma cytokine levels in Malawian children with cerebral malaria. Malar J. 2018;17(1):435. DOI:10.1186/s12936-018-2590-0
  • Quanquin NM, Barres LG, Aliyari SR, et al. Gravidity-dependent associations between interferon response and birth weight in placental malaria. Malar J. 2020;19(1):280. DOI:10.1186/s12936-020-03351-0
  • Hountohotegbe T, Gbedande K, Agbota G, et al. Circulating Cytokines Associated with Poor Pregnancy Outcomes in Beninese Exposed to Infection with Plasmodium falciparum. Infect Immun. 2020;88(8). DOI:10.1128/IAI.00042-20.
  • Fried M, Kurtis JD, Swihart B, et al. Systemic Inflammatory Response to Malaria During Pregnancy is Associated with Pregnancy Loss and Preterm Delivery. Clin Infect Dis. 2017;65(10):1729–1735. DOI:10.1093/cid/cix623
  • Okamgba OC, Ifeanyichukwu MO, Ilesanmi AO, et al. Variations in the leukocyte and cytokine profiles between placental and maternal circulation in pregnancy-associated malaria. Res Rep Trop Med. 2018;9:1–8.
  • Taylor TE, Fu WJ, Carr RA, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med. 2004;10(2):143–145. DOI:10.1038/nm986
  • Reyburn H, Mbatia R, Drakeley C, et al. Association of Transmission Intensity and Age with Clinical Manifestations and Case Fatality of Severe Plasmodium falciparum Malaria. JAMA. 2005;293(12):1461–1470. DOI:10.1001/jama.293.12.1461
  • NAV B, Taylor TE, Harding SP, et al. Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg. 2006;75(5):790–797. DOI:10.4269/ajtmh.2006.75.790
  • Villaverde C, Namazzi R, Shabani E, et al. Retinopathy-Positive Cerebral Malaria is Associated with Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria. J Pediatric Infect Dis Soc. 2020;9(5):580–586. DOI:10.1093/jpids/piz082
  • Villaverde C, Namazzi R, Shabani E, et al. Clinical Comparison of Retinopathy-Positive and Retinopathy-Negative Cerebral Malaria. Am J Trop Med Hyg. 2017;96:1176–1184. DOI:10.4269/ajtmh.16-0315
  • Sahu PK, Duffy FJ, Dankwa S, et al. Determinants of brain swelling in pediatric and adult cerebral malaria. JCI Insight. 2021;6(18):e145823. https://doi.org/10.1172/jci.insight.145823
  • Seydel KB, Kampondeni SD, Molyneux ME, et al. Brain Swelling and Death in Children with Cerebral Malaria. N Engl J Med. 2015;372(12):1126–1137. DOI:10.1056/nejmoa1400116
  • Dondorp AM, Fanello CI, Hendriksen IC, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647–1657. DOI:10.1016/S0140-6736(10)61924-1
  • Idro R, Kakooza-Mwesige A, Asea B, et al. Cerebral malaria is associated with long-term mental health disorders: a cross sectional survey of a long-term cohort. Malar J. 2016;15(1):184. DOI:10.1186/s12936-016-1233-6
  • Boivin MJ, Mohanty A, Sikorskii A, et al. Early and middle childhood developmental, cognitive, and psychiatric outcomes of Malawian children affected by retinopathy positive cerebral malaria. Child Neuropsychol a J Norm Abnorm Dev Child Adolesc. 2019;25(1):81–102. DOI:10.1080/09297049.2018.1451497
  • Brim R, Mboma S, Semrud-Clikeman M, et al. Cognitive Outcomes and Psychiatric Symptoms of Retinopathy-Positive Cerebral Malaria: cohort Description and Baseline Results. Am J Trop Med Hyg. 2017;97(1):225–231. DOI:10.4269/ajtmh.17-0020
  • Datta D, Bangirana P, Opoka RO, et al. Association of Plasma Tau with Mortality and Long-term Neurocognitive Impairment in Survivors of Pediatric Cerebral Malaria and Severe Malarial Anemia. JAMA Network Open. 2021;4(12):e2138515. DOI:10.1001/jamanetworkopen.2021.38515
  • Cabantous S, Poudiougou B, Bergon A, et al. Understanding Human Cerebral Malaria through a Blood Transcriptomic Signature: evidences for Erythrocyte Alteration, Immune/Inflammatory Dysregulation, and Brain Dysfunction. Mediators Inflamm. 2020;2020:3280689. DOI:10.1155/2020/3280689
  • MacCormick IJC, Barrera V, Beare NAV, et al. How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria? J Infect Dis. 2022;225(6):1070–1080. DOI:10.1093/infdis/jiaa541
  • Ponsford MJ, Medana IM, Prapansilp P, et al. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J Infect Dis. 2012;205(4):663–671. DOI:10.1093/infdis/jir812
  • Mohan Rao LV, Esmon CT, Pendurthi UR. Endothelial cell protein C receptor: a multiliganded and multifunctional receptor. Blood. 2014;124(10):1553–1562.
  • Adams Y, Olsen RW, Bengtsson A, et al. Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood–brain barrier in cerebral malaria. J Exp Med. 2021;218(3):e20201266. DOI:10.1084/JEM.20201266
  • Eugenin EA, Martiney JA, Berman JW. The malaria toxin hemozoin induces apoptosis in human neurons and astrocytes: potential role in the pathogenesis of cerebral malaria. Brain Res. 2019;1720:146317.
  • Pal P, Daniels BP, Oskman A, et al. Plasmodium falciparum Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis. MBio. 2016;7(3). https://doi.org/10.1128/mBio.00617-16.
  • Moxon CA, Alhamdi Y, Storm J, et al. Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria. Blood Adv. 2020;4(13):2851–2864. DOI:10.1182/bloodadvances.2019001258
  • Silva LS, Pinheiro AS, Teixeira DE, et al. Kinins Released by Erythrocytic Stages of Plasmodium falciparum Enhance Adhesion of Infected Erythrocytes to Endothelial Cells and Increase Blood Brain Barrier Permeability via Activation of Bradykinin Receptors. Front Med. 2019;6:75. DOI:10.3389/fmed.2019.00075
  • MB VH, Palmer A, Onyiorah E, et al. The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis. 1996;174(5):1091–1097. DOI:10.1093/infdis/174.5.1091
  • Bangirana P, Conroy AL, Opoka RO, et al. Inhaled nitric oxide and cognition in pediatric severe malaria: a randomized double-blind placebo controlled trial. PLoS One. 2018;13(1):e0191550. https://doi.org/10.1371/journal.pone.0191550
  • Ghazanfari N, Mueller SN, Heath WR. Cerebral Malaria in Mouse and Man. Front Immunol. 2018;9:2016.
  • Riggle BA, Manglani M, Maric D, et al. CD8+ T cells target cerebrovasculature in children with cerebral malaria. J Clin Invest. 2020;130(3):1128–1138. DOI:10.1172/JCI133474
  • Barrera V, Haley MJ, Strangward P, et al. Comparison of CD8(+) T Cell Accumulation in the Brain During Human and Murine Cerebral Malaria. Front Immunol. 2019;10:1747. DOI:10.3389/fimmu.2019.01747
  • Moxon CA, Wassmer SC, Milner DAJ, et al. Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children. Blood. 2013;122(5):842–851. https://doi.org/10.1182/blood-2013-03-490219
  • Kho S, Barber BE, Johar E, et al. Platelets kill circulating parasites of all major Plasmodium species in human malaria. Blood. 2018;132(12):1332–1344. https://doi.org/10.1182/blood-2018-05-849307
  • Bridges DJ, Bunn J, van Mourik JA, et al. Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings. Blood. 2010;115(7):1472–1474. https://doi.org/10.1182/blood-2009-07-235150
  • Wassmer SC, de Souza JB, Frère C, et al. TGF-β1 Released from Activated Platelets Can Induce TNF-Stimulated Human Brain Endothelium Apoptosis: a New Mechanism for Microvascular Lesion during Cerebral Malaria. J Immunol. 2006;176(2):1180 LP–1184. DOI:10.4049/jimmunol.176.2.1180
  • Nkosi-Gondwe T, Calis J, Boele van Hensbroek M, et al. A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi. PLoS One. 2021;16(2):e0246267. https://doi.org/10.1371/journal.pone.0246267
  • Green HK, Sousa-Figueiredo JC, Basáñez MG, et al. Anaemia in Ugandan preschool-aged children: the relative contribution of intestinal parasites and malaria. Parasitology. 2011;138(12):1534–1545. DOI:10.1017/S0031182011001016
  • The WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group, Mansoor R, Commons RJ, et al. Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data. BMC Med. 2022;20(1):85.
  • Jakeman GN, Saul A, Hogarth WL, et al. Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytes. Parasitology. 1999;119(Pt 2):127–133.
  • Dondorp AM, Angus BJ, Chotivanich K, et al. Red blood cell deformability as a predictor of anemia in severe falciparum malaria. Am J Trop Med Hyg. 1999;60(5):733–737. DOI:10.4269/ajtmh.1999.60.733
  • Dasari P, Fries A, Heber SD, et al. Malarial anemia: digestive vacuole of Plasmodium falciparum mediates complement deposition on bystander cells to provoke hemophagocytosis. Med Microbiol Immunol. 2014;203(6):383–393. DOI:10.1007/s00430-014-0347-0
  • Oyong DA, Kenangalem E, Poespoprodjo JR, et al. Loss of complement regulatory proteins on uninfected erythrocytes in vivax and falciparum malaria anemia. JCI Insight. 2018;3(22):e124854. https://doi.org/10.1172/jci.insight.124854
  • Pathak V, Colah R, Ghosh K. Plasmodium falciparum malaria skews globin gene expression balance in in-vitro haematopoietic stem cell culture system: its implications in malaria associated anemia. Exp Parasitol. 2018;185:29–38.
  • Thawani N, Tam M, Bellemare M-J, et al. Plasmodium products contribute to severe malarial anemia by inhibiting erythropoietin-induced proliferation of erythroid precursors. J Infect Dis. 2014;209(1):140–149. DOI:10.1093/infdis/jit417
  • Skorokhod OA, Caione L, Marrocco T, et al. Inhibition of erythropoiesis in malaria anemia: role of hemozoin and hemozoin-generated 4-hydroxynonenal. Blood. 2010;116(20):4328–4337. https://doi.org/10.1182/blood-2010-03-272781
  • Opoka RO, Conroy AL, Waiswa A, et al. Severe Anemia is Associated with Systemic Inflammation in Young Children Presenting to a Tertiary Hospital in Uganda. Am J Trop Med Hyg. 2020;103(6):2574–2580. DOI:10.4269/ajtmh.20-0199
  • Punnath K, Dayanand KK, Chandrashekhar VN, et al. Association between inflammatory cytokine levels and anemia during Plasmodium falciparum and Plasmodium vivax infections in Mangaluru: a Southwestern Coastal Region of India. Trop Parasitol. 2019;9(2):98–107. DOI:10.4103/tp.TP_66_18
  • AMR da S V, Fernandes AAM, Zanini GM, et al. Clinical and immunological profiles of anaemia in children and adolescents with Plasmodium vivax malaria in the Pará state, Brazilian Amazon. Acta Trop. 2018;181:122–131. DOI:10.1016/j.actatropica.2018.01.022
  • Lamikanra AA, Merryweather-Clarke AT, Tipping AJ, et al. Distinct mechanisms of inadequate erythropoiesis induced by tumor necrosis factor alpha or malarial pigment. PLoS One. 2015;10(3):e0119836.
  • Jauréguiberry S, Ndour PA, Roussel C, et al. Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins. Blood. 2014;124(2):167–175. https://doi.org/10.1182/blood-2014-02-555953
  • Fanello C, Onyamboko M, Lee SJ, et al. Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria; a randomized comparison of artesunate and quinine. BMC Infect Dis. 2017;17(1):575. DOI:10.1186/s12879-017-2678-0
  • Scheu K, Adegnika AA, Addo MM, et al. Determinants of post-malarial anemia in African children treated with parenteral artesunate. Sci Rep. 2019;9(1):18134. DOI:10.1038/s41598-019-54639-4
  • Rehman K, Lötsch F, Kremsner PG, et al. Haemolysis associated with the treatment of malaria with artemisinin derivatives: a systematic review of current evidence. Int J Infect Dis IJID off Publ Int Soc Infect Dis. 2014;29:268–273.
  • Sagara I, Piarroux R, Djimde A, et al. Delayed anemia assessment in patients treated with oral artemisinin derivatives for uncomplicated malaria: a pooled analysis of clinical trials data from Mali. Malar J. 2014;13(1):358. DOI:10.1186/1475-2875-13-358
  • Rolling T, Wichmann D, Schmiedel S, et al. Artesunate versus quinine in the treatment of severe imported malaria: comparative analysis of adverse events focussing on delayed haemolysis. Malar J. 2013;12(1):241. DOI:10.1186/1475-2875-12-241
  • Hawkes MT, Opoka RO, Conroy AL, et al. Anemia and transfusion requirements among Ugandan children with severe malaria treated with intravenous artesunate. Pediatr Hematol Oncol. 2020;37(2):140–152. DOI:10.1080/08880018.2019.1701161
  • Guenther G, Saidi AM, Izem R, et al. Post-Malaria Anemia is Rare in Malawian Children with Cerebral Malaria. Am J Trop Med Hyg. 2021;104(6):2146–2151. DOI:10.4269/ajtmh.20-1668
  • World Health Organization. WHO Severe malaria 2014. Trop Med Int Heal. 2014;19:7–131. DOI:10.1111/tmi.12313_2
  • Anghan H, Sethi P, Soneja M, et al. Clinical and Laboratory Features Associated with Acute Kidney Injury in Severe Malaria. Indian J Crit Care Med. 2018;22(10):718–722. DOI:10.4103/ijccm.IJCCM_468_17
  • Conroy AL, Opoka RO, Bangirana P, et al. Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria. BMC Med. 2019;17(1):98. DOI:10.1186/s12916-019-1332-7
  • Kaur C, Pramanik A, Kumari K, et al. Renal detection of Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi in malaria associated acute kidney injury: a retrospective case–control study. BMC Res Notes. 2020;13(1):37. DOI:10.1186/s13104-020-4900-1
  • Alexandru S, Ortiz Arduan A, López Picasso M, et al. Fracaso renal agudo anúrico persistente en paciente infectado con Plasmodium malariae: la importancia de la biopsia renal. Nefrología. 2020;40(5):571–573. DOI:10.1016/j.nefro.2019.10.002
  • Hawkes MT, Leligdowicz A, Batte A, et al. Pathophysiology of Acute Kidney Injury in Malaria and Non-Malarial Febrile Illness: a Prospective Cohort Study. Pathogens. 2022;11(4):436. https://doi.org/10.3390/pathogens11040436
  • Nguansangiam S, Day NPJ, Hien TT, et al. A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria. Trop Med Int Health. 2007;12(9):1037–1050. DOI:10.1111/j.1365-3156.2007.01881.x
  • Katsoulis O, Georgiadou A, Cunnington AJ. Immunopathology of Acute Kidney Injury in Severe Malaria. Front Immunol. 2021;12:651739.
  • Plewes K, Kingston HWF, Ghose A, et al. Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. BMC Infect Dis. 2017;17(1):313. DOI:10.1186/s12879-017-2373-1
  • Rivera-Correa J, Conroy AL, Opoka RO, et al. Autoantibody levels are associated with acute kidney injury, anemia and post-discharge morbidity and mortality in Ugandan children with severe malaria. Sci Rep. 2019;9(1):14940. DOI:10.1038/s41598-019-51426-z
  • Silva LS, Peruchetti DB, Silva-Aguiar RP, et al. The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. PLoS One. 2018;13(9):e0203836. https://doi.org/10.1371/journal.pone.0203836
  • Bardají A, Martínez-Espinosa FE, Arévalo-Herrera M, et al. Burden and impact of Plasmodium vivax in pregnancy: a multi-centre prospective observational study. PLoS Negl Trop Dis. 2017;11(6):e0005606. DOI:10.1371/journal.pntd.0005606
  • Dombrowski JG, Barateiro A, Peixoto EPM, et al. Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon. PLoS Negl Trop Dis. 2021;15(4):e0009390. DOI:10.1371/journal.pntd.0009390
  • McGready R, Lee SJ, Wiladphaingern J, et al. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis. 2012;12(5):388–396. DOI:10.1016/S1473-3099(11)70339-5
  • Moore KA, Simpson JA, Scoullar MJL, et al. Quantification of the association between malaria in pregnancy and stillbirth: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(11):e1101–1112. DOI:10.1016/S2214-109X(17)30340-6
  • Bulmer JN, Rasdheed FN, Francis N, et al. Placental malaria. I. Pathological classification. Histopathology. 1993;22(3):211–218. DOI:10.1111/j.1365-2559.1993.tb00110.x
  • Lufele E, Umbers A, Ordi J, et al. Risk factors and pregnancy outcomes associated with placental malaria in a prospective cohort of Papua New Guinean women. Malar J. 2017;16(1):427. DOI:10.1186/s12936-017-2077-4
  • Souza RM, Ataíde R, Dombrowski JG, et al. Placental Histopathological Changes Associated with Plasmodium vivax Infection during Pregnancy. PLoS Negl Trop Dis. 2013;7(2):e2071. DOI:10.1371/journal.pntd.0002071
  • Mayor A, Bardají A, Felger I, et al. Placental infection with Plasmodium vivax: a histopathological and molecular study. J Infect Dis. 2012;206(12):1904–1910. DOI:10.1093/infdis/jis614
  • Ismail MR, Ordi J, Menendez C, et al. Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Hum Pathol. 2000;31(1):85–93. DOI:10.1016/s0046-8177(00)80203-8
  • Crocker IP, Tanner OM, Myers JE, et al. Syncytiotrophoblast Degradation and the Pathophysiology of the Malaria-infected Placenta. Placenta. 2004;25:273–282. DOI:10.1016/j.placenta.2003.09.010
  • Moeller SL, Nyengaard JR, Larsen LG, et al. Malaria in Early Pregnancy and the Development of the Placental Vasculature. J Infect Dis. 2019;220(9):1425–1434. DOI:10.1093/infdis/jiy735
  • Chaikitgosiyakul S, Rijken MJ, Muehlenbachs A, et al. A morphometric and histological study of placental malaria shows significant changes to villous architecture in both Plasmodium falciparum and Plasmodium vivax infection. Malar J. 2014;13(1):4. DOI:10.1186/1475-2875-13-4
  • Rogerson SJ, Pollina E, Getachew A, et al. Placental monocyte infiltrates in response to Plasmodium falciparum malaria infection and their association with adverse pregnancy outcomes. Am J Trop Med Hyg. 2003;68(1):115–119. DOI:10.4269/ajtmh.2003.68.1.0680115
  • Batran SE, Salih MM, Elhassan EM, et al. CD20, CD3, placental malaria infections and low birth weight in an area of unstable malaria transmission in Central Sudan. Diagn Pathol. 2013;8(1):189. DOI:10.1186/1746-1596-8-189
  • Boström S, Schmiegelow C, Abu Abed U, et al. Neutrophil alterations in pregnancy-associated malaria and induction of neutrophil chemotaxis by Plasmodium falciparum. Parasite Immunol. 2017;39(6):e12433. DOI:10.1111/pim.12433
  • Umbers AJ, Boeuf P, Clapham C, et al. Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation. J Infect Dis. 2011;203(4):561–569. DOI:10.1093/infdis/jiq080
  • Menendez C, Ordi J, Ismail MR, et al. The Impact of Placental Malaria on Gestational Age and Birth Weight. J Infect Dis. 2000;181(5):1740–1745. DOI:10.1086/315449
  • Ordi J, Ismail MR, Ventura PJ, et al. Massive Chronic Intervillositis of the Placenta Associated with Malaria Infection. Am J Surg Pathol. 1998;22(8):1006–1011. DOI:10.1097/00000478-199808000-00011
  • Conroy AL, Silver KL, Zhong K, et al. Complement Activation and the Resulting Placental Vascular Insufficiency Drives Fetal Growth Restriction Associated with Placental Malaria. Cell Host Microbe. 2013;13(2):215–226. DOI:10.1016/j.chom.2013.01.010
  • Elphinstone RE, Weckman AM, McDonald CR, et al. Early malaria infection, dysregulation of angiogenesis, metabolism and inflammation across pregnancy, and risk of preterm birth in Malawi: a cohort study. PLoS Med. 2019;16(10):e1002914. DOI:10.1371/journal.pmed.1002914
  • Kabyemela ER, Fried M, Kurtis JD, et al. Fetal responses during placental malaria modify the risk of low birth weight. Infect Immun. 2008;76(4):1527–1534. DOI:10.1128/IAI.00964-07
  • Dobaño C, Bardají A, Arévalo-Herrera M, et al. Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomes. PLoS Negl Trop Dis. 2020;14(5):e0008155. DOI:10.1371/journal.pntd.0008155
  • Singh KP, Shakeel S, Naskar N, et al. Role of IL-1β, IL-6 and TNF-α cytokines and TNF-α promoter variability in Plasmodium vivax infection during pregnancy in endemic population of Jharkhand, India. Mol Immunol. 2018;97:82–93. DOI:10.1016/j.molimm.2018.03.019
  • McDonald CR, Cahill LS, Gamble JL, et al. Malaria in pregnancy alters l-arginine bioavailability and placental vascular development. Sci Transl Med. 2018;10(431):eaan6007. DOI:10.1126/scitranslmed.aan6007
  • Mathenge PG, Low SK, Vuong NL, et al. Efficacy and resistance of different artemisinin-based combination therapies: a systematic review and network meta-analysis. Parasitol Int. 2020;74:101919. DOI:10.1016/j.parint.2019.04.016
  • WWARN K13 Genotype-Phenotype Study. Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments—a WWARN individual patient data meta-analysis. BMC Med. 2019;17(1):1. doi: 10.1186/s12916-018-1207-3.
  • Hamilton WL, Amato R, van der Pluijm RW, et al. Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study. Lancet Infect Dis. 2019;19(9):943–951. DOI:10.1016/S1473-3099(19)30392-5
  • RW VDP, Imwong M, Chau NH, et al. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study. Lancet Infect Dis. 2019;19(9):952–961. DOI:10.1016/S1473-3099(19)30391-3
  • Na-Bangchang K, Muhamad P, Ruaengweerayut R, et al. Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity. Malar J. 2013;12(1):263. DOI:10.1186/1475-2875-12-263
  • Leang R, Taylor WRJ, Bouth DM, et al. Evidence of Plasmodium falciparum Malaria Multidrug Resistance to Artemisinin and Piperaquine in Western Cambodia: dihydroartemisinin-Piperaquine Open-Label Multicenter Clinical Assessment. Antimicrob Agents Chemother. 2015;59(8):4719–4726. DOI:10.1128/AAC.00835-15
  • Smith SJ, Kamara ARY, Sahr F, et al. Efficacy of artemisinin-based combination therapies and prevalence of molecular markers associated with artemisinin, piperaquine and sulfadoxine-pyrimethamine resistance in Sierra Leone. Acta Trop. 2018;185:363–370. DOI:10.1016/j.actatropica.2018.06.016
  • Gansané A, Moriarty LF, Ménard D, et al. Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017–2018. Malar J. 2021;20(1):48. DOI:10.1186/s12936-021-03585-6
  • Kakolwa MA, Mahende MK, Ishengoma DS, et al. Efficacy and safety of artemisinin-based combination therapy, and molecular markers for artemisinin and piperaquine resistance in Mainland Tanzania. Malar J. 2018;17(1):369. DOI:10.1186/s12936-018-2524-x
  • Mayengue PI, Niama RF, Kouhounina Batsimba D, et al. No polymorphisms in K13-propeller gene associated with artemisinin resistance in Plasmodium falciparum isolated from Brazzaville, Republic of Congo. BMC Infect Dis. 2018;18(1):538. DOI:10.1186/s12879-018-3453-6
  • Arya A, Kojom Foko LP, Chaudhry S, et al. Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: a systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa. Int J Parasitol Drugs Drug Resist. 2021;15:43–56. DOI:10.1016/j.ijpddr.2020.11.006
  • Uwimana A, Legrand E, Stokes BH, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020;26(10):1602–1608. DOI:10.1038/s41591-020-1005-2
  • Ikeda M, Kaneko M, Tachibana S-I, et al. Artemisinin - Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014–2016. Emerg Infect Dis. 2018;24(4):718–726. DOI:10.3201/eid2404.170141
  • Scott N, Ataide R, Wilson DP, et al. Implications of population-level immunity for the emergence of artemisinin-resistant malaria: a mathematical model. Malar J. 2018;17(1):279. DOI:10.1186/s12936-018-2418-y
  • Arora T, Sharma S. Global scenario of counterfeit antimalarials: a potential threat. J Vector Borne Dis. 2019;56(4):288–294.
  • Hassett MR, Roepe PD. In vitro growth competition experiments that suggest consequences of the substandard artemisinin epidemic that may be accelerating drug resistance in P. falciparum malaria. PLoS One. 2021;16(3):e0248057.
  • Levin M, Cunnington AJ, Wilson C, et al. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial. Lancet Respir Med. 2019;7(7):581–593. DOI:10.1016/S2213-2600(19)30114-6
  • Meremikwu M, Marson AG. Routine anticonvulsants for treating cerebral malaria. Cochrane Database Syst Rev. 2002;2002:CD002152.
  • Birbeck GL, Herman ST, EV C, et al. A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria. BMC Pediatr. 2019;19(1):399. DOI:10.1186/s12887-019-1766-2
  • Mohanty S, Mishra SK, Patnaik R, et al. Brain swelling and mannitol therapy in adult cerebral malaria: a randomized trial. Clin Infect Dis. 2011;53(4):349–355. DOI:10.1093/cid/cir405
  • Commons RJ, Simpson JA, Thriemer K, et al. The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis. Lancet Infect Dis. 2018;18(9):1025–1034. DOI:10.1016/S1473-3099(18)30348-7
  • Stepniewska K, Humphreys GS, Gonçalves BP, et al. Efficacy of Single-Dose Primaquine with Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: an Individual Patient Meta-Analysis. J Infect Dis. 2022;225(7):1215–1226. DOI:10.1093/infdis/jiaa498
  • Howes RE, Piel FB, Patil AP, et al. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med. 2012;9(11):e1001339. DOI:10.1371/journal.pmed.1001339
  • Lacerda MVG, Llanos-Cuentas A, Krudsood S, et al. Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria. N Engl J Med. 2019;380(3):215–228. DOI:10.1056/NEJMoa1710775
  • Rueangweerayut R, Bancone G, Harrell EJ, et al. Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers. Am J Trop Med Hyg. 2017;97(3):702–711. DOI:10.4269/ajtmh.16-0779
  • Chu CS, Bancone G, Nosten F, et al. Primaquine-induced haemolysis in females heterozygous for G6PD deficiency. Malar J. 2018;17(1):101. DOI:10.1186/s12936-018-2248-y
  • Recht J, Ashley EA, White NJ. Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: divergent policies and practices in malaria endemic countries. PLoS Negl Trop Dis. 2018;12(4):e0006230.
  • Gaudinski MR, Berkowitz NM, Idris AH, et al. A Monoclonal Antibody for Malaria Prevention. N Engl J Med. 2021;385(9):803–814. DOI:10.1056/NEJMoa2034031
  • Bernabeu M, Gunnarsson C, Vishnyakova M, et al. Binding Heterogeneity of Plasmodium falciparum to Engineered 3D Brain Microvessels is Mediated by EPCR and ICAM-1. MBio. 2019;10(3): e00420-19. https://doi.org/10.1128/mBio.00420-19.
  • Sharma A, Jenkins B, Akue A, et al. Plasmodium falciparum in Aotus nancymaae: a New Model for Placental Malaria. J Infect Dis. 2022;226(3):jiac096. DOI:10.1093/infdis/jiac096
  • Schäfer C, Dambrauskas N, Reynolds LM, et al. Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses. Cell Host Microbe. 2021;29(5):752–756.e4. DOI:10.1016/j.chom.2021.03.011
  • McCarthy JS, Griffin PM, Sekuloski S, et al. Experimentally induced blood-stage Plasmodium vivax infection in healthy volunteers. J Infect Dis. 2013;208(10):1688–1694. DOI:10.1093/infdis/jit394
  • Luiza-Batista C, Thiberge S, Serra-Hassoun M, et al. Humanized mice for investigating sustained Plasmodium vivax blood-stage infections and transmission. Nat Commun. 2022;13(1):4123. DOI:10.1038/s41467-022-31864-6
  • Tsuboi T, Del Portillo HA, Mueller I. Editorial on the special issue on Plasmodium vivax: current situation and challenges towards elimination. Parasitol Int. 2022;89:102594.
  • Lee W-C, Cheong FW, Amir A, et al. Plasmodium knowlesi: the game changer for malaria eradication. Malar J. 2022;21(1):140. DOI:10.1186/s12936-022-04131-8