Volume 86, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asunción, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission.


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  1. Vainio J, Cutts F, , 1998. Yellow Fever. Geneva, Switzerland: World Health Organization. [Google Scholar]
  2. Pan American Health Organization, 2008. Outbreak of yellow fever in Paraguay. Epidemiol Bull 27: 2. [Google Scholar]
  3. Soper FL, , 1963. The elimination of urban yellow fever in the Americas through the eradication of Aedes aegypti . Am J Public Health Nations Health 53: 716.[Crossref] [Google Scholar]
  4. Robertson SE, Hull BP, Tomori O, Bele O, LeDuc JW, Esteves K, , 1996. Yellow fever: a decade of reemergence. JAMA 276: 11571162.[Crossref] [Google Scholar]
  5. Gubler DJ, , 1989. Aedes aegypti and Aedes aegypti-borne disease control in the 1990s: top down or bottom up. Charles Franklin Craig Lecture. Am J Trop Med Hyg 40: 571578. [Google Scholar]
  6. Heintze C, Velasco Garrido M, Kroeger A, , 2007. What do community-based dengue control programmes achieve? A systematic review of published evaluations. Trans R Soc Trop Med Hyg 101: 317325.[Crossref] [Google Scholar]
  7. Nathan N, Barry M, Van Herp M, Zeller H, , 2001. Shortage of vaccines during a yellow fever outbreak in Guinea. Lancet 358: 21292130.[Crossref] [Google Scholar]
  8. 2008. Yellow fever preparedness. Lancet 371: 786. [Google Scholar]
  9. Roukens AH, Visser LG, , 2008. Yellow fever vaccine: past, present and future. Expert Opin Biol Ther 8: 17871795.[Crossref] [Google Scholar]
  10. Lindsey NP, Schroeder BA, Miller ER, Braun MM, Hinckley AF, Marano N, Slade BA, Barnett ED, Brunette GW, Horan K, Staples JE, Kozarsky PE, Hayes EB, , 2008. Adverse event reports following yellow fever vaccination. Vaccine 26: 60776082.[Crossref] [Google Scholar]
  11. Whittembury A, Ramirez G, Hernandez H, Ropero AM, Waterman S, Ticona M, Brinton M, Uchuya J, Gershman M, Toledo W, Staples E, Campos C, Martinez M, Chang GJ, Cabezas C, Lanciotti R, Zaki S, Montgomery JM, Monath T, Hayes E, , 2009. Viscerotropic disease following yellow fever vaccination in Peru. Vaccine 27: 59745981.[Crossref] [Google Scholar]
  12. Staples JE, Gershman M, Fischer M, , 2010. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 59: 127. [Google Scholar]
  13. Codeco CT, Luz PM, Struchiner CJ, , 2004. Risk assessment of yellow fever urbanization in Rio de Janeiro, Brazil. Trans R Soc Trop Med Hyg 98: 702710.[Crossref] [Google Scholar]
  14. Johansson MA, Arana-Vizcarrondo N, Biggerstaff BJ, Staples JE, Gallagher N, Marano N, , 2011. On the treatment of airline travelers in mathematical models. PLoS One 6: e22151.[Crossref] [Google Scholar]
  15. New M, Lister D, Hulme M, Makin I, , 2002. A high-resolution data set of surface climate over global land areas. Clim Res 21: 125.[Crossref] [Google Scholar]
  16. Christophers SR, , 1960. Aedes aegypti (L.): The Yellow Fever Mosquito. Cambridge, United Kingdom: The University Press. [Google Scholar]
  17. World Health Organization Department of Immunization Vaccines and Biologicals, 2009. Vaccine Preventable Diseases: Monitoring System. Available at: http://www.who.int/immunization_monitoring/en/globalsummary/timeseries/tsincidenceyfe.htm. Accessed November 4, 2009. [Google Scholar]
  18. Johansson MA, Arana-Vizcarrondo N, Biggerstaff BJ, Staples JE, , 2010. Incubation periods of yellow fever virus. Am J Trop Med Hyg 83: 183188.[Crossref] [Google Scholar]
  19. Focks DA, Haile DG, Daniels E, Mount GA, , 1993. Dynamic life table model for Aedes aegypti (Diptera: Culicidae): analysis of the literature and model development. J Med Entomol 30: 10031017.[Crossref] [Google Scholar]
  20. Getz WM, Lloyd-Smith JO, Feng Z, Dieckmann U, Levin SA, , 2006. Basic methods for modeling the invasion and spread of contagious disease. , eds. Disease Evolution: Models, Concepts, and Data Analysis. Providence, RI: American Mathematical Society, 87109. [Google Scholar]
  21. Koopman JS, Prevots DR, Vaca Marin MA, Gomez Dantes H, Zarate Aquino ML, Longini IM, Jr Sepulveda Amor J, , 1991. Determinants and predictors of dengue infection in Mexico. Am J Epidemiol 133: 11681178.[Crossref] [Google Scholar]
  22. Marques CA, Forattini OP, Massad E, , 1994. The basic reproduction number for dengue fever in Sao Paulo State, Brazil—1990–1991 epidemic. Trans R Soc Trop Med Hyg 88: 5859.[Crossref] [Google Scholar]
  23. Ferguson NM, Donnelly CA, Anderson RM, , 1999. Transmission dynamics and epidemiology of dengue: insights from age-stratified sero-prevalence surveys. Philos Trans R Soc Lond B Biol Sci 354: 757768.[Crossref] [Google Scholar]
  24. Massad E, Burattini MN, Coutinho FA, Lopez LF, , 2003. Dengue and the risk of urban yellow fever reintroduction in Sao Paulo State, Brazil. Rev Saude Publica 37: 477484.[Crossref] [Google Scholar]
  25. Favier C, Degallier N, Rosa-Freitas MG, Boulanger JP, Costa Lima JR, Luitgards-Moura JF, Menkes CE, Mondet B, Oliveira C, Weimann ET, Tsouris P, , 2006. Early determination of the reproductive number for vector-borne diseases: the case of dengue in Brazil. Trop Med Int Health 11: 332340.[Crossref] [Google Scholar]
  26. Chowell G, Diaz-Duenas P, Miller JC, Alcazar-Velazco A, Hyman JM, Fenimore PW, Castillo-Chavez C, , 2007. Estimation of the reproduction number of dengue fever from spatial epidemic data. Math Biosci 208: 571589.[Crossref] [Google Scholar]
  27. Nagao Y, Koelle K, , 2008. Decreases in dengue transmission may act to increase the incidence of dengue hemorrhagic fever. Proc Natl Acad Sci USA 105: 22382243.[Crossref] [Google Scholar]
  28. Rogers DJ, Wilson AJ, Hay SI, Graham AJ, , 2006. The global distribution of yellow fever and dengue. Adv Parasitol 62: 181220.[Crossref] [Google Scholar]
  29. Monath TP, Nasidi A, , 1993. Should yellow fever vaccine be included in the expanded program of immunization in Africa? A cost-effectiveness analysis for Nigeria. Am J Trop Med Hyg 48: 274299. [Google Scholar]
  30. Massad E, Coutinho FA, Burattini MN, Lopez LF, , 2001. The risk of yellow fever in a dengue-infested area. Trans R Soc Trop Med Hyg 95: 370374.[Crossref] [Google Scholar]
  31. Tabachnick WJ, Wallis GP, Aitken TH, Miller BR, Amato GD, Lorenz L, Powell JR, Beaty BJ, , 1985. Oral infection of Aedes aegypti with yellow fever virus: geographic variation and genetic considerations. Am J Trop Med Hyg 34: 12191224. [Google Scholar]
  32. Mitchell CJ, Miller BR, Gubler DJ, , 1987. Vector competence of Aedes albopictus from Houston, Texas, for dengue serotypes 1 to 4, yellow fever and Ross River viruses. J Am Mosq Control Assoc 3: 460465. [Google Scholar]
  33. Lourenco de Oliveira R, Vazeille M, de Filippis AMB, Failloux AB, , 2002. Oral susceptibility to yellow fever virus of Aedes aegypti from Brazil. Mem Inst Oswaldo Cruz 97: 437439.[Crossref] [Google Scholar]
  34. Johnson BW, Chambers TV, Crabtree MB, Filippis AM, Vilarinhos PT, Resende MC, Macoris Mde L, Miller BR, , 2002. Vector competence of Brazilian Aedes aegypti and Ae. albopictus for a Brazilian yellow fever virus isolate. Trans R Soc Trop Med Hyg 96: 611613.[Crossref] [Google Scholar]
  35. Massad E, Coutinho FA, Burattini MN, Lopez LF, Struchiner CJ, , 2005. Yellow fever vaccination: how much is enough? Vaccine 23: 39083914.[Crossref] [Google Scholar]
  36. Codeco CT, Luz PM, Coelho F, Galvani AP, Struchiner C, , 2007. Vaccinating in disease-free regions: a vaccine model with application to yellow fever. J R Soc Interface 4: 11191125.[Crossref] [Google Scholar]
  37. Benedict MQ, Levine RS, Hawley WA, Lounibos LP, , 2007. Spread of the tiger: global risk of invasion by the mosquito Aedes albopictus . Vector Borne Zoonotic Dis 7: 7685.[Crossref] [Google Scholar]
  38. Miller BR, Monath TP, Tabachnick WJ, Ezike VI, , 1989. Epidemic yellow fever caused by an incompetent mosquito vector. Trop Med Parasitol 40: 396399. [Google Scholar]
  39. Lourenco de Oliveira R, Vazeille M, de Filippis AM, Failloux AB, , 2003. Large genetic differentiation and low variation in vector competence for dengue and yellow fever viruses of Aedes albopictus from Brazil, the United States, and the Cayman Islands. Am J Trop Med Hyg 69: 105114. [Google Scholar]
  40. Morrison AC, Gray K, Getis A, Astete H, Sihuincha M, Focks D, Watts D, Stancil JD, Olson JG, Blair P, Scott TW, , 2004. Temporal and geographic patterns of Aedes aegypti (Diptera: Culicidae) production in Iquitos, Peru. J Med Entomol 41: 11231142.[Crossref] [Google Scholar]
  41. Mammen MP, Pimgate C, Koenraadt CJ, Rothman AL, Aldstadt J, Nisalak A, Jarman RG, Jones JW, Srikiatkhachorn A, Ypil-Butac CA, Getis A, Thammapalo S, Morrison AC, Libraty DH, Green S, Scott TW, , 2008. Spatial and temporal clustering of dengue virus transmission in Thai villages. PLoS Med 5: e205.[Crossref] [Google Scholar]
  42. Honorio NA, Nogueira RMR, Codeco CT, Carvalho MS, Cruz OG, Magalhaes MDFM, de Araujo JMG, de Araujo ESM, Gomes MQ, Pinheiro LS, Pinel CD, Lourenco-de-Oliveira R, , 2009. Spatial evaluation and modeling of dengue seroprevalence and vector density in Rio de Janeiro, Brazil. PLoS Negl Trop Dis 3: e545.[Crossref] [Google Scholar]
  43. Vazquez-Prokopec GM, Kitron U, Montgomery B, Horne P, Ritchie SA, , 2010. Quantifying the spatial dimension of dengue virus epidemic spread within a tropical urban environment. PLoS Negl Trop Dis 4: e920.[Crossref] [Google Scholar]
  44. Ackers ML, Puhr ND, Tauxe RV, Mintz ED, , 2000. Laboratory-based surveillance of Salmonella serotype Typhi infections in the United States: antimicrobial resistance on the rise. JAMA 283: 26682673.[Crossref] [Google Scholar]
  45. Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra RM, Nelson JM, Ackers M, Calugar A, Mintz ED, , 2004. Typhoid fever in travelers: who should be targeted for prevention? Clin Infect Dis 39: 186191.[Crossref] [Google Scholar]
  46. Leder K, Tong S, Weld L, Kain KC, Wilder-Smith A, von Sonnenburg F, Black J, Brown GV, Torresi J, , 2006. Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network. Clin Infect Dis 43: 11851193.[Crossref] [Google Scholar]
  47. Skarbinski J, James EM, Causer LM, Barber AM, Mali S, Nguyen-Dinh P, Roberts JM, Parise ME, Slutsker L, Newman RD, , 2006. Malaria surveillance—United States, 2004. MMWR Morb Mortal Wkly Rep 55: 2337. [Google Scholar]
  48. Fenner L, Weber R, Steffen R, Schlagenhauf P, , 2007. Imported infectious disease and purpose of travel, Switzerland. Emerg Infect Dis 13: 217222.[Crossref] [Google Scholar]
  49. US Department of Commerce International Trade Administration, 2009. Profile of US Resident Travelers Visiting Overseas Destinations: 2008 Outbound. Washington, DC: Manufacturing and Services, Office of Travel and Tourism Industries. [Google Scholar]
  50. Theiler M, Anderson CR, , 1975. The relative resistance of dengue-immune monkeys to yellow fever virus. Am J Trop Med Hyg 24: 115117. [Google Scholar]
  51. Monath TP, , 1989. The absence of yellow fever in Asia: hypotheses. A cause for concern? Virus Inf Exch Newsl South East Asia West Pac 6: 106107. [Google Scholar]
  52. Focks DA, Brenner RJ, Hayes J, Daniels E, , 2000. Transmission thresholds for dengue in terms of Aedes aegypti pupae per person with discussion of their utility in source reduction efforts. Am J Trop Med Hyg 62: 1118. [Google Scholar]
  53. Pant CP, Yasuno M, , 1973. Field studies on the gonotrophic cycle of Aedes aegypti in Bangkok, Thailand. J Med Entomol 10: 219223.[Crossref] [Google Scholar]
  54. Scott TW, Amerasinghe PH, Morrison AC, Lorenz LH, Clark GG, Strickman D, Kittayapong P, Edman JD, , 2000. Longitudinal studies of Aedes aegypti (Diptera: Culicidae) in Thailand and Puerto Rico: blood feeding frequency. J Med Entomol 37: 89101.[Crossref] [Google Scholar]
  55. Hindle E, , 1930. The transmission of yellow fever. Lancet 219: 835842.[Crossref] [Google Scholar]

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  • Received : 05 Jul 2011
  • Accepted : 09 Oct 2011
  • Published online : 01 Feb 2012

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