World Health Organization , 2021. World Malaria Report 2021. Geneva, Switzerland: WHO. Available at: https://apps.who.int/iris/rest/bitstreams/1398397/retrieve. Accessed May 1, 2022.
Howes RE, Battle KE, Mendis KN, Smith DL, Cibulskis RE, Baird JK, Hay SI, 2016. Global epidemiology of Plasmodium vivax. Am J Trop Med Hyg 95: 15–34.
Battle KE, Baird JK, 2021. The global burden of Plasmodium vivax malaria is obscure and insidious. PLoS Med 18: e1003799.
Miller LH, Mason SJ, Clyde DF, McGinnis MH, 1976. The resistance factor to Plasmodium vivax in Blacks: the Duffy blood group genotype, FyFy. N Engl J Med 295: 302–304.
Barnwell JW, Nichols ME, Rubinstein R, 1989. In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax. J Exp Med 169: 1795–1802.
Langhi DM Jr, Bordin JO, 2006. Duffy blood group and malaria. Hematology 11: 389–398.
Menard D et al., 2010. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA 107: 5967–5971.
Howes RE et al., 2015. Plasmodium vivax transmission in Africa. PLoS Negl Trop Dis 9: e0004222.
Lo E et al., 2019. Frequent expansion of Plasmodium vivax Duffy binding protein in Ethiopia and its epidemiological significance. PLoS Negl Trop Dis 13: e0007222.
Ketema T, Bacha K, Getahun K, Portillo HAD, Bassat Q, 2021. Plasmodium vivax epidemiology in Ethiopia 2000–2020: a systematic review and meta-analysis. PLoS Negl Trop Dis 15: e0009781.
Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM, 2007. Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77 (Suppl ):79–87.
Baum E et al., 2015. Submicroscopic and asymptomatic Plasmodium falciparum and Plasmodium vivax infections are common in western Thailand—molecular and serological evidence. Malar J 14: 95.
Baird JK, 2021. Basic research of Plasmodium vivax biology enabling its management as a clinical and public health problem. Front Cell Infect Microbiol 11: 696598.
Corran P, Coleman P, Riley E, Drakeley C, 2007. Serology: a robust indicator of malaria transmission intensity? Trends Parasitol 23: 575–582.
Cook J, Reid H, Iavro J, Kuwahata M, Taleo G, Clements A, McCarthy J, Vallely A, Drakeley C, 2010. Using serological measures to monitor changes in malaria transmission in Vanuatu. Malar J 9: 169.
Yman V, White MT, Rono J, Arcà B, Osier FH, Troye-Blomberg M, Boström S, Ronca R, Rooth I & Färnert A et al., 2016. Antibody acquisition models: a new tool for serological surveillance of malaria transmission intensity. Sci Rep 6: 19472.
van den Hoogen LL et al., 2015. Serology describes a profile of declining malaria transmission in Farafenni, The Gambia. Malar J 14: 416.
Assefa A et al., 2019. Multiplex serology demonstrate cumulative prevalence and spatial distribution of malaria in Ethiopia. Malar J 18: 246.
Ntumngia FB, Schloegel J, Barnes SJ, McHenry AM, Singh S, King CL, Adams JH, 2012. Conserved and variant epitopes of Plasmodium vivax Duffy binding protein as targets of inhibitory monoclonal antibodies. Infect Immun 80: 1203–1208.
Payne RO et al., 2017. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight 2: e93683.
Hawaria D, Getachew H, Zhou G, Demissew A, Habitamu K, Raya B, Lee MC, Yewhalaw D, Yan G, 2019. Ten years malaria trend at Arjo-Didessa sugar development site and its vicinity, southwest Ethiopia: a retrospective study. Malar J 18: 145.
Taffese HS, Hemming-Schroeder E, Koepfli C, Tesfaye G, Lee MC, Kazura J, Yan G, Zhou G, 2018. Malaria epidemiology and interventions in Ethiopia from 2001 to 2016. Infect Dis Poverty 7: 6.
Bereczy SMA, Gil JP, Farnert A, 2005. Short report: rapid DNA extraction from archive blood spots on filter paper for genotyping Plasmodium falciparum. Am J Trop Med Hyg 72: 249–251.
Veron V, Simon S, Carme B, 2009. Multiplex real-time PCR detection of P. falciparum, P. vivax and P. malariae in human blood samples. Exp Parasitol 121: 346–351.
Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK, 2009. Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol 47: 975–980.
Wurtz NL et al., 2011. Vivax malaria in Maritania includes infection of a Duffy-negative individual. Malar J 10: 336.
Dent AE et al., 2016. Contrasting patterns of serologic and functional antibody dynamics to Plasmodium falciparum antigens in a Kenyan birth cohort. Clin Vaccine Immunol 23: 104–116.
Weber GE et al., 2017. Sero-catalytic and antibody acquisition models to estimate differing malaria transmission intensities in western Kenya. Sci Rep 7: 16821.
Howes RE et al., 2011. The global distribution of the Duffy blood group. Nat Commun 2: 266.
Woldearegai TG, Kremsner PG, Kun JF, Mordmuller B, 2013. Plasmodium vivax malaria in Duffy-negative individuals from Ethiopia. Trans R Soc Trop Med Hyg 107: 328–331.
Wertheimer SP, Barnwell JW, 1989. Plasmodium vivax interaction with the human Duffy blood group glycoprotein: identification of a parasite receptor-like protein. Exp Parasitol 69: 340–350.
Zimmerman PA, 2017. Plasmodium vivax infection in Duffy-negative people in Africa. Am J Trop Med Hyg 97: 636–638.
Mendes C, Dias F, Figueiredo J, Mora VG, Cano J, de Sousa B, do Rosario VE, Benito A, Berzosa P, Arez AP, 2011. Duffy negative antigen is no longer a barrier to Plasmodium vivax—molecular evidences from the African West Coast (Angola and Equatorial Guinea). PLoS Negl Trop Dis 5: e1192.
Ngassa Mbenda HG, Das A, 2014. Molecular evidence of Plasmodium vivax mono and mixed malaria parasite infections in Duffy-negative native Cameroonians. PLoS One 9: e103262.
Kepple D et al., 2021. Plasmodium vivax from Duffy-negative and Duffy-positive individuals share similar gene pools in East Africa. J Infect Dis 224: 1422–1431.
Oguariri RM, Borrmann S, Klinkert MQ, Kremsner PG, Kun JF, 2001. High prevalence of human antibodies to recombinant Duffy binding–like alpha domains of the Plasmodium falciparum–infected erythrocyte membrane protein 1 in semi-immune adults compared to that in nonimmune children. Infect Immun 69: 7603–7609.
Howell DP, Levin EA, Springer AL, Kraemer SM, Phippard DJ, Schief WR, Smith JD, 2008. Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors. Mol Microbiol 67: 78–87.
Mavoungou E, Held J, Mewono L, Kremsner PG, 2007. A Duffy binding–like domain is involved in the NKp30-mediated recognition of Plasmodium falciparum-parasitized erythrocytes by natural killer cells. J Infect Dis 195: 1521–1531.
Wang R et al., 2005. Immune responses to Plasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens. Eur J Immunol 35: 1859–1868.
Wang Q et al., 2016. Naturally acquired antibody responses to Plasmodium vivax and Plasmodium falciparum merozoite surface protein 1 (MSP1) C-terminal 19 kDa domains in an area of unstable malaria transmission in Southeast Asia. PLoS One 11: e0151900.
Kano FS et al., 2018. Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria. Sci Rep 8: 1–14.
Muh F et al., 2020. Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi. PLoS Negl Trop Dis 14: e0008323.
Priest JW, Plucinski MM, Huber CS, Rogier E, Mao B, Gregory CJ, Candrinho B, Colborn J, Barnwell JW, 2018. Specificity of the IgG antibody response to Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale MSP119 subunit proteins in multiplexed serologic assays. Malar J 17: 417.
Herrera SV et al., 2005. Antibody response to Plasmodium vivax antigens in Fy-negative individuals from the Colombian Pacific coast. Am J Trop Med Hyg 73: 44–49.
Maestre A et al., 2010. Acquired antibody responses against Plasmodium vivax infection vary with host genotype for Duffy antigen receptor for chemokines (DARC). PLoS One 5: e11437.
Cui L, Brashear A, Menezes L, Adams J & Rodriguez-Morales AJ Current Topics and Emerging Issues in Malaria Elimination. London, United Kingdom: IntechOpen, 1–27.
De SL, May S, Shah K, Slawinski M, Changrob S, Xu S, Barnes SJ, Chootong P, Ntumngia FB, Adams JH, 2021. Variable immunogenicity of a vivax malaria blood-stage vaccine candidate. Vaccine 39: 2668–2675.
Kearney EA, Agius PA, Chaumeau V, Cutts JC, Simpson JA, Fowkes FJI, 2021. Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: a systematic review with multilevel modelling. eLife 10: e73080.
Wilairatana P, Masangkay FR, Kotepui KU, De Jesus Milanez G, Kotepui M, 2022. Prevalence and risk of Plasmodium vivax infection among Duffy-negative individuals: a systematic review and meta-analysis. Sci Rep 12: 3998.
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Despite historical dogma that Duffy blood group negativity of human erythrocytes confers resistance to Plasmodium vivax blood stage infection, cases of P. vivax malaria and asymptomatic blood stage infection (subclinical malaria) have recently been well documented in Duffy-negative individuals throughout Africa. However, the impact of Duffy negativity on the development of naturally acquired immunity to P. vivax remains poorly understood. We examined antibody reactivity to P. vivax and P. falciparum antigens at two field sites in Ethiopia and assessed Duffy gene expression by polymerase chain reaction amplification and sequencing of the GATA-1 transcription factor–binding site of the Duffy antigen receptor for chemokines (DARC) gene promotor region that is associated with silencing of erythroid cell transcription and absent protein expression. Antibodies to three of the four P. vivax blood stage antigens examined, RBP2b, EBP2, and DBPIISal-1, were significantly lower (P < 0.001) in Duffy-negative individuals relative to Duffy-positive individuals. In stark contrast, no clear pattern was found across Duffy-negative and Duffy-positive genotypes for P. falciparum antibodies. We conclude that lack of erythroid Duffy expression is associated with reduced serologic responses, indicative of less naturally acquired immunity and less cumulative exposure to blood stage P. vivax parasites relative to Duffy positive individuals living in the same communities.
Financial support: This study was funded by the
Disclaimer: This work was presented in part at the American Society for Tropical Medicine and Hygiene Annual Meeting 2021.
Authors’ addresses: Lauren Bradley, Department of Ecology and Evolutionary Biology, University of California, Irvine, CA, E-mail: lbradle1@uci.edu. Delenasaw Yewhalaw, Department of Medical Laboratory Sciences and Pathology, College of Health Sciences, and Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia, E-mail: delenasawye@yahoo.com. Elizabeth Hemming-Schroeder, Center for Vector-Borne Infectious Diseases, Colorado State University, Fort Collins, CO, E-mail: Elizabeth.Hemming-Schroeder@colostate.edu. Paula Embury, Christopher King, James Kazura, and Arlene Dent, Center for Global Health and Disease, Case Western Reserve University, Cleveland, OH, E-mails: pbe@case.edu, cxk21@case.edu, jxk14@case.edu, and aed9@case.edu. Ming-Chieh Lee, Program in Public Health, College of Health Sciences, University of California, Irvine, CA, E-mail: mingchil@uci.edu. Endalew Zemene, Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia, E-mail: endalew2005@yahoo.com. Teshome Degefa, School of Medical Laboratory Sciences, Faculty of Health Sciences, Jimma University, Jimma, Ethiopia, E-mail: teshedege@gmail.com. Guiyun Yan, Department of Ecology and Evolutionary Biology, School of Biological Sciences and Program in Public Health, College of Health Sciences, University of California, Irvine, CA, E-mail: guiyuny@hs.uci.edu.
World Health Organization , 2021. World Malaria Report 2021. Geneva, Switzerland: WHO. Available at: https://apps.who.int/iris/rest/bitstreams/1398397/retrieve. Accessed May 1, 2022.
Howes RE, Battle KE, Mendis KN, Smith DL, Cibulskis RE, Baird JK, Hay SI, 2016. Global epidemiology of Plasmodium vivax. Am J Trop Med Hyg 95: 15–34.
Battle KE, Baird JK, 2021. The global burden of Plasmodium vivax malaria is obscure and insidious. PLoS Med 18: e1003799.
Miller LH, Mason SJ, Clyde DF, McGinnis MH, 1976. The resistance factor to Plasmodium vivax in Blacks: the Duffy blood group genotype, FyFy. N Engl J Med 295: 302–304.
Barnwell JW, Nichols ME, Rubinstein R, 1989. In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax. J Exp Med 169: 1795–1802.
Langhi DM Jr, Bordin JO, 2006. Duffy blood group and malaria. Hematology 11: 389–398.
Menard D et al., 2010. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA 107: 5967–5971.
Howes RE et al., 2015. Plasmodium vivax transmission in Africa. PLoS Negl Trop Dis 9: e0004222.
Lo E et al., 2019. Frequent expansion of Plasmodium vivax Duffy binding protein in Ethiopia and its epidemiological significance. PLoS Negl Trop Dis 13: e0007222.
Ketema T, Bacha K, Getahun K, Portillo HAD, Bassat Q, 2021. Plasmodium vivax epidemiology in Ethiopia 2000–2020: a systematic review and meta-analysis. PLoS Negl Trop Dis 15: e0009781.
Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM, 2007. Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77 (Suppl ):79–87.
Baum E et al., 2015. Submicroscopic and asymptomatic Plasmodium falciparum and Plasmodium vivax infections are common in western Thailand—molecular and serological evidence. Malar J 14: 95.
Baird JK, 2021. Basic research of Plasmodium vivax biology enabling its management as a clinical and public health problem. Front Cell Infect Microbiol 11: 696598.
Corran P, Coleman P, Riley E, Drakeley C, 2007. Serology: a robust indicator of malaria transmission intensity? Trends Parasitol 23: 575–582.
Cook J, Reid H, Iavro J, Kuwahata M, Taleo G, Clements A, McCarthy J, Vallely A, Drakeley C, 2010. Using serological measures to monitor changes in malaria transmission in Vanuatu. Malar J 9: 169.
Yman V, White MT, Rono J, Arcà B, Osier FH, Troye-Blomberg M, Boström S, Ronca R, Rooth I & Färnert A et al., 2016. Antibody acquisition models: a new tool for serological surveillance of malaria transmission intensity. Sci Rep 6: 19472.
van den Hoogen LL et al., 2015. Serology describes a profile of declining malaria transmission in Farafenni, The Gambia. Malar J 14: 416.
Assefa A et al., 2019. Multiplex serology demonstrate cumulative prevalence and spatial distribution of malaria in Ethiopia. Malar J 18: 246.
Ntumngia FB, Schloegel J, Barnes SJ, McHenry AM, Singh S, King CL, Adams JH, 2012. Conserved and variant epitopes of Plasmodium vivax Duffy binding protein as targets of inhibitory monoclonal antibodies. Infect Immun 80: 1203–1208.
Payne RO et al., 2017. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight 2: e93683.
Hawaria D, Getachew H, Zhou G, Demissew A, Habitamu K, Raya B, Lee MC, Yewhalaw D, Yan G, 2019. Ten years malaria trend at Arjo-Didessa sugar development site and its vicinity, southwest Ethiopia: a retrospective study. Malar J 18: 145.
Taffese HS, Hemming-Schroeder E, Koepfli C, Tesfaye G, Lee MC, Kazura J, Yan G, Zhou G, 2018. Malaria epidemiology and interventions in Ethiopia from 2001 to 2016. Infect Dis Poverty 7: 6.
Bereczy SMA, Gil JP, Farnert A, 2005. Short report: rapid DNA extraction from archive blood spots on filter paper for genotyping Plasmodium falciparum. Am J Trop Med Hyg 72: 249–251.
Veron V, Simon S, Carme B, 2009. Multiplex real-time PCR detection of P. falciparum, P. vivax and P. malariae in human blood samples. Exp Parasitol 121: 346–351.
Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK, 2009. Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol 47: 975–980.
Wurtz NL et al., 2011. Vivax malaria in Maritania includes infection of a Duffy-negative individual. Malar J 10: 336.
Dent AE et al., 2016. Contrasting patterns of serologic and functional antibody dynamics to Plasmodium falciparum antigens in a Kenyan birth cohort. Clin Vaccine Immunol 23: 104–116.
Weber GE et al., 2017. Sero-catalytic and antibody acquisition models to estimate differing malaria transmission intensities in western Kenya. Sci Rep 7: 16821.
Howes RE et al., 2011. The global distribution of the Duffy blood group. Nat Commun 2: 266.
Woldearegai TG, Kremsner PG, Kun JF, Mordmuller B, 2013. Plasmodium vivax malaria in Duffy-negative individuals from Ethiopia. Trans R Soc Trop Med Hyg 107: 328–331.
Wertheimer SP, Barnwell JW, 1989. Plasmodium vivax interaction with the human Duffy blood group glycoprotein: identification of a parasite receptor-like protein. Exp Parasitol 69: 340–350.
Zimmerman PA, 2017. Plasmodium vivax infection in Duffy-negative people in Africa. Am J Trop Med Hyg 97: 636–638.
Mendes C, Dias F, Figueiredo J, Mora VG, Cano J, de Sousa B, do Rosario VE, Benito A, Berzosa P, Arez AP, 2011. Duffy negative antigen is no longer a barrier to Plasmodium vivax—molecular evidences from the African West Coast (Angola and Equatorial Guinea). PLoS Negl Trop Dis 5: e1192.
Ngassa Mbenda HG, Das A, 2014. Molecular evidence of Plasmodium vivax mono and mixed malaria parasite infections in Duffy-negative native Cameroonians. PLoS One 9: e103262.
Kepple D et al., 2021. Plasmodium vivax from Duffy-negative and Duffy-positive individuals share similar gene pools in East Africa. J Infect Dis 224: 1422–1431.
Oguariri RM, Borrmann S, Klinkert MQ, Kremsner PG, Kun JF, 2001. High prevalence of human antibodies to recombinant Duffy binding–like alpha domains of the Plasmodium falciparum–infected erythrocyte membrane protein 1 in semi-immune adults compared to that in nonimmune children. Infect Immun 69: 7603–7609.
Howell DP, Levin EA, Springer AL, Kraemer SM, Phippard DJ, Schief WR, Smith JD, 2008. Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors. Mol Microbiol 67: 78–87.
Mavoungou E, Held J, Mewono L, Kremsner PG, 2007. A Duffy binding–like domain is involved in the NKp30-mediated recognition of Plasmodium falciparum-parasitized erythrocytes by natural killer cells. J Infect Dis 195: 1521–1531.
Wang R et al., 2005. Immune responses to Plasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens. Eur J Immunol 35: 1859–1868.
Wang Q et al., 2016. Naturally acquired antibody responses to Plasmodium vivax and Plasmodium falciparum merozoite surface protein 1 (MSP1) C-terminal 19 kDa domains in an area of unstable malaria transmission in Southeast Asia. PLoS One 11: e0151900.
Kano FS et al., 2018. Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria. Sci Rep 8: 1–14.
Muh F et al., 2020. Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi. PLoS Negl Trop Dis 14: e0008323.
Priest JW, Plucinski MM, Huber CS, Rogier E, Mao B, Gregory CJ, Candrinho B, Colborn J, Barnwell JW, 2018. Specificity of the IgG antibody response to Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale MSP119 subunit proteins in multiplexed serologic assays. Malar J 17: 417.
Herrera SV et al., 2005. Antibody response to Plasmodium vivax antigens in Fy-negative individuals from the Colombian Pacific coast. Am J Trop Med Hyg 73: 44–49.
Maestre A et al., 2010. Acquired antibody responses against Plasmodium vivax infection vary with host genotype for Duffy antigen receptor for chemokines (DARC). PLoS One 5: e11437.
Cui L, Brashear A, Menezes L, Adams J & Rodriguez-Morales AJ Current Topics and Emerging Issues in Malaria Elimination. London, United Kingdom: IntechOpen, 1–27.
De SL, May S, Shah K, Slawinski M, Changrob S, Xu S, Barnes SJ, Chootong P, Ntumngia FB, Adams JH, 2021. Variable immunogenicity of a vivax malaria blood-stage vaccine candidate. Vaccine 39: 2668–2675.
Kearney EA, Agius PA, Chaumeau V, Cutts JC, Simpson JA, Fowkes FJI, 2021. Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: a systematic review with multilevel modelling. eLife 10: e73080.
Wilairatana P, Masangkay FR, Kotepui KU, De Jesus Milanez G, Kotepui M, 2022. Prevalence and risk of Plasmodium vivax infection among Duffy-negative individuals: a systematic review and meta-analysis. Sci Rep 12: 3998.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1092 | 1092 | 152 |
Full Text Views | 64 | 64 | 29 |
PDF Downloads | 64 | 64 | 34 |