Negative Duffy defense strategy: resistance mechanisms against vivax malaria
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Abstract
The Duffy blood type system consists of three alleles: FY*A, FY*B, and FYnull, leading to four phenotypes: Fy (a+b+), Fy (a–b+), Fy (a+b–), and Fy (a–b–). The Fy (a–b–) phenotype, which lacks both FY*A and FY*B alleles and other Duffy antigens, is predominantly found in native African populations and is associated with resistance to vivax malaria infection. Despite this, rare cases of vivax malaria have been reported in individuals with the Fy (a–b–) phenotype in Papua New Guinea. An evolutionary perspective reveals that the Duffy glycoprotein (DARC) binds chemokines from both Cysteine — any amino acid — Cysteine (C-X-C) and Cysteine — Cysteine (CC) classes and interacts with the malaria parasites Plasmodium vivax and Plasmodium knowlesi. Diagnosis of vivax malaria can be confirmed using microscopic examination and Rapid Diagnostic Tests (RDTs). Treatment options including chloroquine and primaquine effectively reduce parasitemia, mitigate direct risk to the host, prevent infection, and interrupt the transmission cycle.
Keywords: Duffy glycoproteinDuffy blood groupvivax malariaPlasmodium knowlesiPlasmodium vivax
References
- Talapko J, Škrlec I, Alebić T, et al. Malaria: The Past and the Present. Microorganisms. 2019; 7(6).
- WHO. World Malaria Report 2023. Geneva: World Health Organization; 2023. https://iris.who.int/bitstream/handle/10665/374472/9789240086173-eng.pdf?sequence=1.
- ISBT. Red Cell Immunogenetics and Blood Group Terminology. https://www.isbtweb.org/isbt-working-parties/rcibgt.html.
- Aldarweesh FA. The Duffy Blood Group System. Human Blood Group Systems and Haemoglobinopathies. 2021.
- Dean L. Blood Groups and Red Cell Antigens [Internet]. In: Bethesda (MD). National Center for Biotechnology Information 2005.
- Howes RE, Patil AP, Piel FB, et al. The global distribution of the Duffy blood group. Nat Commun. 2011; 2: 266.
- Höher G, Fiegenbaum M, Almeida S. Duffy Blood Group System. Human Blood Groups. 2018; 16(1): 93–100.
- Hulden L, Hulden L. Activation of the hypnozoite: a part of Plasmodium vivax life cycle and survival. Malar J. 2011; 10: 90.
- Mueller I, Galinski MR, Baird JK, et al. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis. 2009; 9(9): 555–566.
- Sorontou Y, Kes M. Ilmu Malaria Klinik [Clinical Malaria Science]. Penerbit Buku Kedokteran EGC, Jakarta 2014.
- Sucipto CD. Manual Lengkap Malaria [Complete Manual Of Malaria]. Yogyakarta: Gosyen Publishing 2015: 197.
- Baird JK, Valecha N, Duparc S, et al. Diagnosis and Treatment of Plasmodium vivax Malaria. Am J Trop Med Hyg. 2016; 95(6 Suppl): 35–51.
- Menkin-Smith L, Winders WT. Plasmodium vivax Malaria. StatPearls Publishing LLC 2023.
- de Carvalho GB, de Carvalho GB. Duffy Blood Group System and the malaria adaptation process in humans. Rev Bras Hematol Hemoter. 2011; 33(1): 55–64.
- Reid M, Lomas-Francis C. P blood group system. The Blood Group Antigen FactsBook. 2004: 105–108.
- Daniels G. Human Blood Groups. 2nd ed. USA: Blackwell Science Ltd 2002.
- Písačka M, Marinov I, Králová M, et al. FY*A silencing by the GATA-motif variant FY*A(-69C) in a Caucasian family. Transfusion. 2015; 55(11): 2616–2619.
- Daniels G, Bromilow I. Essential Guide to Blood Groups. 2nd ed. A John Wiley & Sons 2010.
- Zimmerman PA, Ferreira MU, Howes RE, et al. Red blood cell polymorphism and susceptibility to Plasmodium vivax. Adv Parasitol. 2013; 81: 27–76.
- Gunalan K, Lo E, Hostetler JB, et al. Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans. Proc Natl Acad Sci U S A. 2016; 113(22): 6271–6276.
- Weppelmann TA, Carter TE, Chen Z, et al. High frequency of the erythroid silent Duffy antigen genotype and lack of Plasmodium vivax infections in Haiti. Malar J. 2013; 12: 30.
- McManus KF, Taravella AM, Henn BM, et al. Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans. PLoS Genet. 2017; 13(3): e1006560.