Parasite genotypes and host immune mediators in primary and recurrent episodes of vivax Malaria in Colombia
DOI:
https://doi.org/10.17843/rpmesp.2025.424.14865Keywords:
Malaria, Plasmodium vivax, Recurrence, Pregnancy, Genotypes, CytokinesAbstract
Objectives. To identify Plasmodium vivax genotypes in the pregnant and non-pregnant population and explore their association with immune mediators. Materials and methods. Two cohorts of patients with uncomplicated vivax malaria were followed for 120 days in Puerto Libertador and Tierralta, Cordoba, Co-lombia: 41 pregnant women and 46 non- pregnant individuals, all treated with standard treatment. Parasite genotypes (microsatellites Pv3.27, Pv3.502, and Pv1.501) and the expression of host immune mediators (IL-13, IL-10, TNF- alpha, IFN-gamma, IL-8, TGF-beta, Fox-P3, PD-L1) were compared between primary and recurrent infections. Results. The frequency of recurrences was higher in pregnant women (41.6%) than in non-pregnant individuals (8.7%). Parasite genetic diversity was higher in pregnant women, al-though without exclusive alleles. Recurrences were genetically homologous (same alleles) in only 23% and 33% of cases in pregnant and non-pregnant individuals, respectively. Regarding immune mediators, only Fox-P3 expression varied significantly in pregnant women, with higher expression in the primary episode than in the recurrent one. Conclusions. Pregnant women are exposed to a high frequency of vivax malaria recurrences, with high parasite genetic variation, which may affect the development of effective protective immunity and favor adverse obstetric outcomes, both maternal and neonatal. These findings raise the need to strengthen and optimize prevention and treatment actions for vivax malaria during pregnancy.
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References
López-Guzmán C, Carmona-Fonseca J. Submicroscopic placental malaria: histopathology and expression of physiological process
mediators. Rev Peru Med Exp Salud Publica 2020;37:220–8. doi: 10.17843/rpmesp.2020.372.4759.
Bôtto-Menezes C, Silva Dos Santos MC, Lopes Simplício J, Menezes de Medeiros J, Barroso Gomes KC, de Carvalho Costa IC, et al. Plasmodium vivax Malaria in Pregnant Women in the Brazilian Amazon and the Risk Factors Associated with Prematurity and Low Birth Weight: A Descriptive Study. PLoS One 2015;10:e0144399. doi: 10.1371/journal.pone.0144399.
Agudelo OM, Aristizabal BH, Yanow SK, Arango E, Carmona-Fonseca J, Maestre A. Submicroscopic infection of placenta by Plasmodium
produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia. Malar J. 2014;13:122. doi: 10.1186/1475-2875-13-122.
Bardají A, Martínez-Espinosa FE, Arévalo-Herrera M, Padilla N, Kochar S, Ome-Kaius M, et al. Burden and impact of Plasmodium vivax in pregnancy: A multi-centre prospective observational study. PLoS Negl Trop Dis. 2017;11:e0005606. doi: 10.1371/journal.pntd.0005606.
Global Malaria Programme (GMP). World malaria report 2024. Addressing inequity in the global malaria response. World Health Organization; 2024.
Cardona-Arias JA, Higuita-Gutiérrez LF, Carmona-Fonseca J. Clinical and Parasitological Profiles of Gestational, Placental and Congenital Malaria in Northwestern Colombia. Trop Med Infect Dis 2023;8:292. doi: 10.3390/tropicalmed8060292.
Carmona-Fonseca J, Arango E, Maestre A. Placental malaria in Colombia: histopathologic findings in Plasmodium vivax and P. falciparum infections. Am J Trop Med Hyg. 2013;88:1093–101. doi: 10.4269/ajtmh.12-0363.
Carmona-Fonseca J, Agudelo-García O, Arango-Flórez E. Eficacia terapéutica y eventos adversos de tratamientos para malaria vivax y malaria falciparum en gestantes en las regiones de Urabá y Alto San Jorge, Colombia, 2008-2011. Rev Colomb Obstet Ginecol. 2013;64:27–37.
Dombrowski JG, Barateiro A, Peixoto EPM, Barros ABC da S, Souza RM de, Clark TG, 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:e0009390. doi: 10.1371/journal.pntd.0009390.
White NJ, Imwong M. Relapse. Adv Parasitol. 2012;80:113–50. doi: 10.1016/B978-0-12-397900-1.00002-5.
Carmona-Fonseca J. Recurrencias de malaria por Plasmodium vivax según el uso de primaquina: análisis de estudios descriptivos longitudinales. Rev Bras Epidemiol. 2012;15:488–503. doi: 10.1590/S1415-790X2012000300005.
Baird JK, Maguire JD, Price RN. Diagnosis and Treatment of Plasmodium vivax Malaria. In: Hay SI, Price R, Baird JK, editors. Adv Parasitol., vol. 80, Academic Press; 2012, p. 203–70. doi: 10.1016/B978-0-12-397900-1.00004-9.
Carmona-Fonseca J, Maestre A. Prevention of Plasmodium vivax malaria recurrence: efficacy of the standard total dose of primaquine administered over 3 days. Acta Trop. 2009;112:188–92. doi: 10.1016/j.actatropica.2009.07.024.
Battle KE, Karhunen MS, Bhatt S, Gething PW, Howes RE, Golding N, et al. Geographical variation in Plasmodium vivax relapse. Malar J. 2014;13:144. doi: 10.1186/1475-2875-13-144.
Markus MB. Malaria Eradication and the Hidden Parasite Reservoir. Trends Parasitol. 2017;33:492–5. doi: 10.1016/j.pt.2017.03.002.
Markus MB. Biological concepts in recurrent Plasmodium vivax malaria. Parasitology. 2018;145:1765–71. doi: 10.1017/S003118201800032X.
Siegel SV, Amato R, Trimarsanto H, Sutanto E, Kleinecke M, Murie K, et al. Lineage-informative microhaplotypes for spatio-temporal surveillance of. medRxiv. 2023. doi: 10.1101/2023.03.13.23287179.
Spiegelenberg JP, Bastiaens GJH, Hassing R-J. Treatment of relapsing Plasmodium vivax malaria during pregnancy. J Travel Med. 2021;28:taab087. doi: 10.1093/jtm/taab087.
Global Malaria Programme (GMP), Guidelines Review Committee. WHO guidelines for malaria. World Health Organization; 2025.
White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J. 2011;10:297. doi: 10.1186/1475-2875-10-297.
Maneerattanasak S, Gosi P, Krudsood S, Chimma P, Tongshoob J, Mahakunkijcharoen Y, et al. Molecular and immunological analyses of confirmed Plasmodium vivax relapse episodes. Malar J. 2017;16:228. doi: 10.1186/s12936-017-1877-x.
Chaves YO, da Costa AG, Pereira MLM, de Lacerda MVG, Coelho-Dos-Reis JG, Martins-Filho OA, et al. Immune response pattern in recurrent Plasmodium vivax malaria. Malar J. 2016;15:445. doi: 10.1186/s12936-016-1501-5.
Hojo-Souza NS, Pereira DB, Passos LS, Gazzinelli-Guimarães PH, Cardoso MS, Tada MS, et al. Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection. BMC Infect Dis. 2015;15:35. doi: 10.1186/s12879-015-0762-x.
Neafsey DE, Galinsky K, Jiang RH, Young L, Sykes SM, Saif S, et al. The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum. Nat Genet. 2012;44:1046–50. doi: 10.1038/ng.2373.
Fola AA, Harrison GLA, Hazairin MH, Barnadas C, Hetzel MW, Iga J, et al. Higher Complexity of Infection and Genetic Diversity of Plasmodium vivax Than Plasmodium falciparum across all Malaria Transmission Zones of Papua New Guinea. Am J Trop Med Hyg. 2017;96:630–41. doi: 10.4269/ajtmh.16-0716.
Imwong M, Boel ME, Pagornrat W, Pimanpanarak M, McGready R, Day NP, et al. The first Plasmodium vivax relapses of life are usually genetically homologous. J Infect Dis. 2012;205:680–3. doi: 10.1093/infdis/jir806.
Gonzalez-Ceron L, Mu J, Santillán F, Joy D, Sandoval MA, Camas G, et al. Molecular and epidemiological characterization of Plasmodium vivax recurrent infections in southern Mexico. Parasit Vectors. 2013;6:109. doi: 10.1186/1756-3305-6-109.
Zuluaga-Idárraga L, Blair S, Akinyi Okoth S, Udhayakumar V, Marcet PL, Escalante AA, et al. Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia. Antimicrob Agents Chemother. 2016;60:4610–9. doi: 10.1128/AAC.00186-16.
Restrepo E, Imwong M, Rojas W, Carmona-Fonseca J, Maestre A. High genetic polymorphism of relapsing P. vivax isolates in northwest Colombia. Acta Trop. 2011;119:23–9. doi: 10.1016/j.actatropica.2011.03.012.
Mor G, Cardenas I. The Immune System in Pregnancy: A Unique Complexity. Am J Reprod Immunol N Y N. 1989 2010;63:425–33. doi: 10.1111/j.1600-0897.2010.00836.x.
Carmona-Fonseca J. La Región “Urabá Antioqueño-Cuencas altas de los ríos Sinú y San Jorge-Bajo Cauca Antioqueño”: “guarida” del paludismo colombiano. Rev Univ Ind Santander Salud Online. 2017;49:577–89.
Olivera MJ, Padilla Rodriguez JC, Narváez PEC, Quevedo WL. Epidemiology of Plasmodium vivax malaria infection in Colombia. The
Microbe. 2024;5:100209. doi: 10.1016/j.microb.2024.100209.
Castro-Cavadía CJ, Carmona-Fonseca J. Assessment of the efficacy and safety of chloroquine monotherapy for the treatment of acute
uncomplicated gestational malaria caused by P. vivax, Córdoba, Colombia, 2015-2017. Rev Colomb Obstet Ginecol. 2020;71:21–33. doi: 10.18597/rcog.3370.
Organización Mundial de la Salud. Bases del diagnóstico microscópico del paludismo: Parte1. Guía del alumno. 2nd ed. Suiza: World Health Organization; 2015.
Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK. Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol. 2009;47:975–80. doi: 10.1128/JCM.01858-08.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE. Pyrimeth falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995;52:565–8.
Koepfli C, Mueller I, Marfurt J, Goroti M, Sie A, Oa O, et al. Evaluation of Plasmodium vivax genotyping markers for molecular monitoring in clinical trials. J Infect Dis. 2009;199:1074–80. doi: 10.1086/597303.
Koepfli C, Timinao L, Antao T, Barry AE, Siba P, Mueller I, et al. A Large Plasmodium vivax Reservoir and Little Population Structure in the South Pacific. PLoS One. 2013;8(6):e66041. doi: 10.1371/journal.pone.0066041.
Imwong M, Nair S, Pukrittayakamee S, Sudimack D, Williams JT, Mayxay M, et al. Contrasting genetic structure in Plasmodium vivax populations from Asia and South America. Int J Parasitol. 2007;37:1013–22. doi: 10.1016/j.ijpara.2007.02.010.
Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A, et al. Relapses of Plasmodium vivax infection usually
result from activation of heterologous hypnozoites. J Infect Dis. 2007;195:927–33. doi: 10.1086/512241.
Álvarez‐Larrotta C, Agudelo OM, Duque Y, Gavina K, Yanow SK, Maestre A, et al. Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid. Clin Exp Immunol. 2019;195:96–108. doi: 10.1111/cei.13213.
Cristiano FA, Pérez MA, Nicholls RS, Guerra AP. Polymorphism in the Plasmodium vivax msp 3: gene in field samples from Tierralta,
Colombia. Mem Inst Oswaldo Cruz. 2008;103:493–6. doi: 10.1590/s0074-02762008000500015.
Winter DJ, Pacheco MA, Vallejo AF, Schwartz RS, Arevalo-Herrera M, Herrera S, et al. Whole Genome Sequencing of Field Isolates Reveals Extensive Genetic Diversity in Plasmodium vivax from Colombia. PLoS Negl Trop Dis. 2015;9:e0004252. doi: 10.1371/journal.pntd.0004252.
Arango EM, Samuel R, Agudelo OM, Carmona-Fonseca J, Maestre A, Yanow SK. Genotype comparison of Plasmodium vivax and Plasmodium falciparum clones from pregnant and non-pregnant populations in Northwest Colombia. Malar J. 2012;11:392. doi: 10.1186/1475-2875-11-392.
Pacheco MA, Schneider KA, Céspedes N, Herrera S, Arévalo-Herrera M, Escalante AA. Limited differentiation among Plasmodium vivax populations from the northwest and to the south Pacific Coast of Colombia: A malaria corridor?. PLoS Negl Trop Dis. 2019;13:e0007310. doi: 10.1371/journal.pntd.0007310.
Menegon M, Bardají A, Martínez-Espinosa F, Bôtto-Menezes C, Ome--Kaius M, Mueller I, et al. Microsatellite Genotyping of Plasmodium vivax Isolates from Pregnant Women in Four Malaria Endemic Countries. PLoS One 2016;11:e0152447. doi: 10.1371/journal.pone.0152447.
Alvarez G, Piñeros JG, Tobón A, Ríos A, Maestre A, Blair S, et al. Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium vivax malaria in Colombia. Am J Trop Med Hyg 2006;75:605–9.
de Araujo FC, de Rezende AM, Fontes CJ, Carvalho LH, Alves de Brito CF. Multiple-clone activation of hypnozoites is the leading cause of relapse in Plasmodium vivax
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