{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:57:24Z","timestamp":1760057844291,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Econom\u00eda y Finanzas (MEF)","award":["111.1.3.04.14","173-2021"],"award-info":[{"award-number":["111.1.3.04.14","173-2021"]}]},{"name":"Instituto Conmemorativo Gorgas de Estudios de la Salud in Panama City, Panam\u00e1","award":["111.1.3.04.14","173-2021"],"award-info":[{"award-number":["111.1.3.04.14","173-2021"]}]},{"name":"Sistema Nacional de Investigaci\u00f3n","award":["111.1.3.04.14","173-2021"],"award-info":[{"award-number":["111.1.3.04.14","173-2021"]}]},{"name":"Indiana University","award":["111.1.3.04.14","173-2021"],"award-info":[{"award-number":["111.1.3.04.14","173-2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>This study evaluated the genetic diversity and potential drug resistance markers in Plasmodium vivax isolates from Panama, a country in Mesoamerica, aiming to eliminate local malaria transmission. We analyzed 70 P. vivax samples collected between 2004 and 2020 from endemic regions in Eastern and Western Panama, as well as imported cases. Four drug resistance genes (pvcrt-o, pvmdr1, pvdhfr, and pvdhps) were sequenced and analyzed. Our findings reveal low genetic diversity in P. vivax populations from Western Panama, indicating clonal expansion, while Eastern Panama exhibits higher diversity, influenced by higher transmission rates and imported cases. No mutations were detected in pvcrt-o, and the prevalence of pvmdr1 mutations (Y976F and F1076L) linked to chloroquine was observed at low frequencies, primarily in imported samples. In pvdhfr, antifolate-resistant mutations S117N and S58R were detected in 14.3% of samples, predominantly from Eastern Panama near the Colombian border. Phylogenetic and haplotype network analyses highlighted distinct genetic clustering, supporting the influence of imported cases on local parasite diversity. These results provide a baseline for the molecular surveillance of P. vivax in Panama and emphasize the need for the continued monitoring of genetic diversity and drug resistance to guide regional malaria elimination efforts, particularly in areas with high cross-border migration.<\/jats:p>","DOI":"10.3390\/pathogens14030231","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T05:13:58Z","timestamp":1740633238000},"page":"231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Diversity of Potential Drug Resistance Markers in Plasmodium vivax Isolates from Panama, Mesoamerica"],"prefix":"10.3390","volume":"14","author":[{"given":"Vanessa","family":"V\u00e1squez","sequence":"first","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Parasitolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Mar\u00eda","family":"Santamar\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Parasitolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianik","family":"Moreno","sequence":"additional","affiliation":[{"name":"Laboratorio Central de Referencia en Salud Publica, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fergie","family":"Ru\u00edz","sequence":"additional","affiliation":[{"name":"Laboratorio Central de Referencia en Salud Publica, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-6511","authenticated-orcid":false,"given":"Chystrie A.","family":"Rigg","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Parasitolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-2764","authenticated-orcid":false,"given":"Luis F.","family":"Chaves","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, IN 47408, USA"},{"name":"Department of Geography, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6669-4290","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Calzada","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Parasitolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panam\u00e1 0816-02593, Panama"},{"name":"Facultad de Medicina Veterinaria, Universidad de Panam\u00e1, Panam\u00e1 0816-3366, Panama"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2018). Update on the e-2020 Initiative of 21 Malaria-Eliminating Countries: Report and Country Briefs, WHO. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/273633\/WHO-CDS-GMP-2018.13-eng.pdf?sequence=1&isAllowed=y."},{"key":"ref_2","unstructured":"Iniciativa Regional de Eliminaci\u00f3n de la Malaria en Mesoam\u00e9rica (IREM) (2024, March 11). Bolet\u00edn Informativo de Implementaci\u00f3n de Acciones: Abril\u2013Junio. Available online: https:\/\/www.proyectomesoamerica.org\/index.php\/noticias\/20-noticiaspm\/articulos-noticias\/1056-irem-boletin-informativo-de-implementacion-de-acciones-abril-junio-2023."},{"key":"ref_3","unstructured":"World Health Organization (WHO) (2023). World Malaria Report 2023, WHO. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2023."},{"key":"ref_4","unstructured":"World Health Organization (WHO) (2021). World Malaria Day: WHO Launches Effort to Stamp Out Malaria in 25 More Countries by 2025, WHO. Available online: https:\/\/www.who.int\/news\/item\/21-04-2021-world-malaria-day-who-launches-effort-to-stamp-out-malaria-in-25-more-countries-by-2025."},{"key":"ref_5","unstructured":"Pan American Health Organization (PAHO) (2021). Plan of Action for Malaria Elimination 2021\u20132025, PAHO. Available online: https:\/\/iris.paho.org\/bitstream\/handle\/10665.2\/56616\/PAHOCDEVT220005_eng.pdf?sequence=1&isAllowed=y."},{"key":"ref_6","unstructured":"Ministerio de Salud de Panam\u00e1 (MINSA) (2024, March 12). Plan Estrat\u00e9gico de Eliminaci\u00f3n de la Malaria (PEEM) en Panam\u00e1 2018\u20132022. Panam\u00e1, Rep\u00fablica de Panam\u00e1, Available online: https:\/\/www.minsa.gob.pa\/sites\/default\/files\/direcciones\/guia_integrada_malaria_2021.pdf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12936-020-03329-y","article-title":"Long-term transmission patterns and public health policies leading to malaria elimination in Panam\u00e1","volume":"19","author":"Hurtado","year":"2020","journal-title":"Malar. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/jmedent\/45.5.841","article-title":"Species composition and distribution of adult Anopheles (Diptera: Culicidae) in Panama","volume":"45","author":"Loaiza","year":"2008","journal-title":"J. Med. Entomol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1186\/s12936-024-05208-2","article-title":"Pilot introduction of long-lasting insecticidal nets and hammock nets in the indigenous Comarca of Guna Yala, Panama","volume":"23","author":"Perez","year":"2024","journal-title":"Malar. J."},{"key":"ref_10","unstructured":"World Health Organization (WHO) (2020). Report on Antimalarial Drug Efficacy, Resistance and Response: 10 Years of Surveillance (2010\u20132019), WHO. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240012813."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ijpddr.2020.12.001","article-title":"Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions","volume":"15","author":"Ferreira","year":"2021","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_12","unstructured":"Ministerio de Salud de Panam\u00e1 (MINSA) (2024, March 12). Manual de Normas y Procedimientos Para Malaria. Panam\u00e1, Rep\u00fablica de Panam\u00e1, Available online: https:\/\/www.minsa.gob.pa\/sites\/default\/files\/publicaciones\/manualnormayprocmalaria.pdf."},{"key":"ref_13","first-page":"100505","article-title":"Migrants in transit across Central America and the potential spread of chloroquine resistant malaria-a call for action","volume":"22","author":"Suarez","year":"2023","journal-title":"Lancet Reg. Health-Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijpddr.2021.04.002","article-title":"The molecular basis of antimalarial drug resistance in Plasmodium vivax","volume":"16","author":"Buyon","year":"2021","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/s12936-020-03519-8","article-title":"Molecular surveillance of the Plasmodium vivax multidrug resistance 1 gene in Peru between 2006 and 2015","volume":"19","author":"Villena","year":"2020","journal-title":"Malar. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s40249-022-00964-2","article-title":"Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China-Myanmar border during 2008\u20132017","volume":"11","author":"Wang","year":"2022","journal-title":"Infect. Dis. Poverty"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0166-6851(93)90050-8","article-title":"Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections","volume":"58","author":"Snounou","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.actatropica.2010.08.011","article-title":"Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries","volume":"117","author":"Lu","year":"2011","journal-title":"Acta Trop."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Suwanarusk, R., Russell, B., Chavchich, M., Chalfein, F., Kenangalem, E., Kosaisavee, V., Prasetyorini, B., Piera, K.A., Barends, M., and Brockman, A. (2007). Chloroquine resistant Plasmodium vivax: In vitro characterisation and association with molecular polymorphisms. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0001089"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3347\/kjp.2012.50.4.379","article-title":"Prevalence of drug resistance-associated gene mutations in Plasmodium vivax in Central China","volume":"50","author":"Lu","year":"2012","journal-title":"Korean J. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis Version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Munro, H.N. (1969). Evolution of Protein Molecules. Mammalian Protein Metabolism, Academic Press.","DOI":"10.1016\/B978-1-4832-3211-9.50010-3"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1111\/2041-210X.12410","article-title":"Popart: Full-feature software for haplotype network construction","volume":"6","author":"Leigh","year":"2015","journal-title":"Methods Ecol. Evol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1093\/molbev\/msx248","article-title":"DnaSP 6: DNA Sequence Polymorphism Analysis of Large Data Sets","volume":"34","author":"Rozas","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cumbrera, A., Calzada, J.E., Chaves, L.F., and Hurtado, L.A. (2024). Spatiotemporal Analysis of Malaria Transmission in the Autonomous Indigenous Regions of Panama, Central America, 2015\u20132022. Trop. Med. Infect. Dis., 9.","DOI":"10.3390\/tropicalmed9040090"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Santamar\u00eda, A.M., V\u00e1squez, V., Rigg, C., Moreno, D., Romero, L., Justo, C., Chaves, L.F., Salda\u00f1a, A., and Calzada, J.E. (2020). Plasmodium falciparum Genetic Diversity in Panam\u00e1 Based on glurp, msp-1 and msp-2 Genes: Implications for Malaria Elimination in Mesoamerica. Life, 10.","DOI":"10.3390\/life10120319"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Santamar\u00eda, A.M., V\u00e1squez, V., Rigg, C., Samudio, F., Moreno, D., Romero, L., Salda\u00f1a, A., Chaves, L.F., and Calzada, J.E. (2021). Plasmodium vivax Genetic Diversity in Panama: Challenges for Malaria Elimination in Mesoamerica. Pathogens, 10.","DOI":"10.3390\/pathogens10080989"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Valdivia, H.O., Villena, F.E., Lizewski, S.E., Garcia, J., Alger, J., and Bishop, D.K. (2020). Genomic surveillance of Plasmodium falciparum and Plasmodium vivax cases at the University Hospital in Tegucigalpa, Honduras. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-78103-w"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.trstmh.2008.03.012","article-title":"Revising antimalarial drug policy in Central America: Experience in Panama","volume":"102","author":"Calzada","year":"2008","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1186\/s12936-016-1543-8","article-title":"Geographic distribution of amino acid mutations in DHFR and DHPS in Plasmodium vivax isolates from Lao PDR, India and Colombia","volume":"15","author":"Saralamba","year":"2016","journal-title":"Malar. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"364","DOI":"10.21149\/10129","article-title":"Molecular variation of Plasmodium vivax dehydrofolate reductase in Mexico and Nicaragua contrasts with that occurring in South America","volume":"62","author":"Montoya","year":"2020","journal-title":"Salud Publica Mex."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12936-022-04084-y","article-title":"Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar","volume":"21","author":"Huang","year":"2022","journal-title":"Malar. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1186\/s12936-015-0903-0","article-title":"Distribution of Plasmodium vivax pvdhfr and pvdhps alleles and their association with sulfadoxine-pyrimethamine treatment outcomes in Indonesia","volume":"14","author":"Asih","year":"2015","journal-title":"Malar. J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Buyon, L.E., Santamaria, A.M., Early, A.M., Quijada, M., Barahona, I., Lasso, J., Avila, M., Volkman, S.K., Marti, M., and Neafsey, D.E. (2020). Population genomics of Plasmodium vivax in Panama to assess the risk of case importation on malaria elimination. PLoS Negl. Trop. Dis., 14.","DOI":"10.1101\/2020.08.26.267823"},{"key":"ref_35","first-page":"100230","article-title":"Genetic diversity of Plasmodium vivax and Plasmodium falciparum field isolates from Honduras in the malaria elimination phase","volume":"21","author":"Zamora","year":"2024","journal-title":"Curr. Res. Parasitol. Vector-Borne Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chaves, L.F., Huber, J.H., Rojas Salas, O., Ram\u00edrez Rojas, M., Romero, L.M., Guti\u00e9rrez Alvarado, J.M., Perkins, T.A., Prado, M., and Marin Rodr\u00edguez, R. (2020). Malaria Elimination in Costa Rica: Changes in Treatment and Mass Drug Administration. Microorganisms, 8.","DOI":"10.3390\/microorganisms8070984"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.pt.2019.04.007","article-title":"Parasite Removal for Malaria Elimination in Costa Rica","volume":"35","author":"Chaves","year":"2019","journal-title":"Trends Parasitol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/3\/231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:43:24Z","timestamp":1760028204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/3\/231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["pathogens14030231"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14030231","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2025,2,27]]}}}