Volume 90, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Although the geographic origin of malaria cases imported into the United States can often be inferred from travel histories, these histories may be lacking or incomplete. We hypothesized that mitochondrial haplotypes could provide region-specific molecular barcodes for tracing the origin of imported infections. An analysis of 348 mitochondrial genomes from worldwide parasites and new sequences from 69 imported malaria cases diagnosed across the United States allowed for a geographic assignment of most infections originating from the Americas, southeast Asia, east Asia, and Melanesia. However, mitochondrial lineages from Africa, south Asia, central Asia, and the Middle East, which altogether contribute the vast majority of imported malaria cases in the United States, were closely related to each other and could not be reliably assigned to their geographic origins. More mitochondrial genomes are required to characterize molecular barcodes of from these regions.


Article metrics loading...

Loading full text...

Full text loading...



  1. Franco-Paredes C, Santos-Preciado JI, , 2006. Problem pathogens: prevention of malaria in travellers. Lancet Infect Dis 6: 139149.[Crossref]
  2. Leder K, Torresi J, Brownstein JS, Wilson ME, Keystone JS, Barnett E, Schwartz E, Schlagenhauf P, Wilder-Smith A, Castelli F, von Sonnenburg F, Freedman DO, Cheng AC, , 2013. Travel-associated illness trends and clusters, 2000–2010. Emerg Infect Dis 19: 10491073.[Crossref]
  3. Nilles EJ, Arguin PM, , 2012. Imported malaria: an update. Am J Emerg Med 30: 972980.[Crossref]
  4. Mali S, Kachur SP, Arguin PM, , 2012. Malaria surveillance—United States, 2010. MMWR Surveill Summ 61: 117.
  5. Rosenberg R, , 2007. Plasmodium vivax in Africa: hidden in plain sight? Trends Parasitol 23: 193196.[Crossref]
  6. Schwartz E, Parise M, Kozarsky P, Cetron M, , 2003. Delayed onset of malaria—implications for chemoprophylaxis in travelers. N Engl J Med 349: 15101516.[Crossref]
  7. Bottieau E, Clerinx J, Van Den Enden E, Van Esbroeck M, Colebunders R, Van Gompel A, Van Den Ende J, , 2006. Imported non-Plasmodium falciparum malaria: a five-year prospective study in a European referral center. Am J Trop Med Hyg 75: 133138.
  8. Armengaud A, Legros F, D'Ortenzio E, Quatresous I, Barre H, Houze S, Valayer P, Fanton Y, Schaffner F, , 2008. A case of autochthonous Plasmodium vivax malaria, Corsica, August 2006. Travel Med Infect Dis 6: 36.[Crossref]
  9. Sainz-Elipe S, Latorre JM, Escosa R, Masià M, Fuentes MV, Mas-Coma S, Bargues MD, , 2010. Malaria resurgence risk in southern Europe: climate assessment in a historically endemic area of rice fields at the Mediterranean shore of Spain. Malar J 9: 221.[Crossref]
  10. Odolini S, Gautret P, Parola P, , 2012. Epidemiology of imported malaria in the Mediterranean region. Mediterr J Hematol Infect Dis 4: e2012031.[Crossref]
  11. Romi R, Boccolini D, Menegon M, Rezza G, , 2012. Probable autochthonous introduced malaria cases in Italy in 2009–2011 and the risk of local vector-borne transmission. Euro Surveill 17: 20325.
  12. Shkurti K, Vyshka G, Velo E, Boçari A, Kokici M, Kraja D, , 2013. Imported malaria in Albania and the risk factors that could allow its reappearance. Malar J 12: 197.[Crossref]
  13. Tatem AJ, Smith DL, , 2010. International population movements and regional Plasmodium falciparum malaria elimination strategies. Proc Natl Acad Sci USA 107: 1222212227.[Crossref]
  14. Le Menach A, Tatem AJ, Cohen JM, Hay SI, Randell H, Patil AP, Smith DL, , 2011. Travel risk, malaria importation and malaria transmission in Zanzibar. Sci Rep 1: 93.[Crossref]
  15. Al-Farsi HM, Al-Hashami ZS, Bin Dajem SM, Al-Sheikh AA, Al-Qahtani A, Beja-Pereira A, Idris MA, Babiker HA, , 2012. Source of drug resistant Plasmodium falciparum in a potential malaria elimination site in Saudi Arabia. Infect Genet Evol 12: 12531259.[Crossref]
  16. Galappaththy GN, Fernando SD, Abeyasinghe RR, , 2013. Imported malaria: a possible threat to the elimination of malaria from Sri Lanka? Trop Med Int Health 18: 761768.[Crossref]
  17. Choi KM, Choi YK, Kang YA, Seo SY, Lee HW, Cho SH, Lee WJ, Rhie HG, Lee HS, Kim JY, , 2011. Study of the genetic discrimination between imported and autochthonous cases of malaria in South Korea. J Travel Med 18: 6366.[Crossref]
  18. Severini C, Menegon M, Gradoni L, Majori G, , 2002. Use of the Plasmodium vivax merozoite surface protein 1 gene sequence analysis in the investigation of an introduced malaria case in Italy. Acta Trop 84: 151157.[Crossref]
  19. Conway DJ, Fanello C, Lloyd JM, Al-Joubori BM, Baloch AH, Somanath SD, Roper C, Oduola AM, Mulder B, Povoa MM, Singh B, Thomas AW, , 2000. Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Mol Biochem Parasitol 111: 163171.[Crossref]
  20. Joy DA, Feng X, Mu J, Furuya T, Chotivanich K, Krettli AU, Ho M, Wang A, White NJ, Suh E, Beerli P, Su XZ, , 2003. Early origin and recent expansion of Plasmodium falciparum . Science 300: 318321.[Crossref]
  21. Johnston SP, Pieniazek NJ, Xayavong MV, Slemenda SB, Wilkins PP, da Silva AJ, , 2006. PCR as a confirmatory technique for laboratory diagnosis of malaria. J Clin Microbiol 44: 10871089.[Crossref]
  22. Miao M, Yang Z, Patch H, Huang Y, Escalante AA, Cui L, , 2012. Plasmodium vivax populations revisited: mitochondrial genomes of temperate strains in Asia suggest ancient population expansion. BMC Evol Biol 12: 22.[Crossref]
  23. Mu J, Joy DA, Duan J, Huang Y, Carlton J, Walker J, Barnwell J, Beerli P, Charleston MA, Pybus OG, Su XZ, , 2005. Host switch leads to emergence of Plasmodium vivax malaria in humans. Mol Biol Evol 22: 16861693.[Crossref]
  24. Jongwutiwes S, Putaporntip C, Iwasaki T, Ferreira MU, Kanbara H, Hughes AL, , 2005. Mitochondrial genome sequences support ancient population expansion in Plasmodium vivax . Mol Biol Evol 22: 17331739.[Crossref]
  25. Iwagami M, Hwang SY, Fukumoto M, Hayakawa T, Tanabe K, Kim SH, Kho WG, Kano S, , 2010. Geographical origin of Plasmodium vivax in the Republic of Korea: haplotype network analysis based on the parasite's mitochondrial genome. Malar J 9: 184.[Crossref]
  26. Culleton R, Coban C, Zeyrek FY, Cravo P, Kaneko A, Randrianarivelojosia M, Andrianaranjaka V, Kano S, Farnert A, Arez AP, Sharp PM, Carter R, Tanabe K, , 2011. The origins of African Plasmodium vivax; insights from mitochondrial genome sequencing. PLoS ONE 6: e29137.[Crossref]
  27. da Silva-Nunes M, Moreno M, Conn JE, Gamboa D, Abeles S, Vinetz JM, Ferreira MU, , 2012. Amazonian malaria: asymptomatic human reservoirs, diagnostic challenges, environmentally driven changes in mosquito vector populations, and the mandate for sustainable control strategies. Acta Trop 121: 281291.[Crossref]
  28. Ronquist F, Teslenko M, van der Mark P, Ayres DL, Darling A, Höhna S, Larget B, Liu L, Suchard MA, Huelsenbeck JP, , 2012. MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space. Syst Biol 61: 539542.[Crossref]
  29. Huson DH, Richter DC, Rausch C, Dezulian T, Franz M, Rupp R, , 2007. Dendroscope: an interactive viewer for large phylogenetic trees. BMC Bioinformatics 8: 460.[Crossref]
  30. Bandelt H-J, Forster P, Röhl A, , 1999. Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol 16: 3748.[Crossref]
  31. Karunaweera ND, Ferreira MU, Munasinghe A, Barnwell JW, Collins WE, King CL, Kawamoto F, Hartl DL, Wirth DF, , 2008. Extensive microsatellite diversity in the human malaria parasite Plasmodium vivax . Gene 410: 105112.[Crossref]
  32. Gunawardena S, Karunaweera ND, Ferreira MU, Phone-Kyaw M, Pollack RJ, Alifrangis M, Rajakaruna RS, Konradsen F, Amerasinghe PH, Schousboe ML, Galappaththy GN, Abeyasinghe RR, Hartl DL, Wirth DF, , 2010. Geographic structure of Plasmodium vivax: microsatellite analysis of parasite populations from Sri Lanka, Myanmar, and Ethiopia. Am J Trop Med Hyg 82: 235242.[Crossref]
  33. Gupta B, Srivastava N, Das A, , 2012. Inferring the evolutionary history of Indian Plasmodium vivax from population genetic analyses of multilocus nuclear DNA fragments. Mol Ecol 21: 15971616.[Crossref]
  34. Ferreira MU, Karunaweera ND, da Silva-Nunes M, da Silva NS, Wirth DF, Hartl DL, , 2007. Population structure and transmission dynamics of Plasmodium vivax in rural Amazonia. J Infect Dis 195: 12181226.[Crossref]
  35. Orjuela-Sánchez P, Karunaweera ND, da Silva-Nunes M, da Silva NS, Scopel KKG, Gonçalves RM, Amaratunga C, JM, Socheat D, Fairhust RM, Gunawardena S, Thavakodirasah T, Galapaththy GL, Abeysinghe R, Kawamoto F, Wirth DF, Ferreira MU, , 2010. Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies. BMC Genet 11: 65.[Crossref]
  36. Van den Eede P, Van der Auwera G, Delgado C, Huyse T, Soto-Calle VE, Gamboa D, Grande T, Rodriguez H, Llanos A, Anné J, Erhart A, D'Alessandro U, , 2010. Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon. Malar J 9: 151.[Crossref]
  37. Taylor JE, Pacheco MA, Bacon DJ, Beg MA, Machado RL, Fairhurst RM, Herrera S, Kim JY, Menard D, Póvoa MM, Villegas L, Mulyanto Snounou G, Cui L, Zeyrek FY, Escalante AA, , 2013. The evolutionary history of Plasmodium vivax as inferred from mitochondrial genomes: parasite genetic diversity in the Americas. Mol Biol Evol 30: 20502064.[Crossref]

Data & Media loading...

Supplementary Data

Supplementary PDF

  • Received : 11 Oct 2013
  • Accepted : 06 Feb 2014

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error