Volume 84, Issue 2_Suppl
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Vaccine development for malaria is underway. A model to assess the protective efficacy of vaccine candidates in humans is urgently needed. Given the lack of continuous cultures, we developed a system to infect mosquitoes using blood from infected patients and determined parameters for challenge of malaria-naive volunteers by mosquito bite. Absence of co-infections in parasitized blood was confirmed by tests consistent with blood bank screening. A total of 119 experiments were conducted using batches of 900–4,500 mosquitoes fed by an artificial membrane feeding method. Optimal conditions for mosquito probing and infection were determined. Presence of oocyst and sporozoites were assessed on Days 7–8 and 14–15, respectively, and conditions to choose batches of infected mosquitoes for sporozoite challenge were established. Procedures to infect volunteers took a 2-hour period including verification of inoculum dose. mosquitoes represent a valuable resource for sporozoite challenge of volunteers.


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  1. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitie MA, Dubovsky F, Menendez C, Tornieporth N, Ballou WR, Thompson R, Cohen J, , 2004. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364: 14111420.[Crossref] [Google Scholar]
  2. Moreno CA, Rodriguez R, Oliveira GA, Ferreira V, Nussenzweig RS, Moya Castro ZR, Calvo-Calle JM, Nardin E, , 1999. Preclinical evaluation of a synthetic Plasmodium falciparum MAP malaria vaccine in Aotus monkeys and mice. Vaccine 18: 8999.[Crossref] [Google Scholar]
  3. Roggero MA, Weilenmann C, Bonelo A, Audran R, Renggli J, Spertini F, Corradin G, Lopez JA, , 1999. Plasmodium falciparum CS C-terminal fragment: preclinical evaluation and phase I clinical studies. Parassitologia 41: 421424. [Google Scholar]
  4. Mullen GE, Giersing BK, Ajose-Popoola O, Davis HL, Kothe C, Zhou H, Aebig J, Dobrescu G, Saul A, Long CA, , 2006. Enhancement of functional antibody responses to AMA1-C1/Alhydrogel, a Plasmodium falciparum malaria vaccine, with CpG oligodeoxynucleotide. Vaccine 24: 24972505.[Crossref] [Google Scholar]
  5. Ballou WR, Arévalo-Herrera M, Carucci D, Richie TL, Corradin G, Diggs C, Druilhe P, Giersing BK, Saul A, Heppner DG, Kester KE, Lanar DE, Lyon J, Hill AV, Pan W, Cohen JD, , 2004. Update on the clinical development of candidate malaria vaccines. Am J Trop Med Hyg 71: 239247. [Google Scholar]
  6. Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, Sacci J, de la Vega P, Dowler M, Paul C, Gordon DM, Stoute JA, Church LW, Sedegah M, Heppner DG, Ballou WR, Richie TL, , 2002. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis 185: 11551164.[Crossref] [Google Scholar]
  7. Epstein JE, Rao S, Williams F, Freilich D, Luke T, Sedegah M, de la Vega P, Sacci J, Richie TL, Hoffman SL, , 2007. Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. J Infect Dis 196: 145154.[Crossref] [Google Scholar]
  8. Silvie O, Semblat JP, Franetich JF, Hannoun L, Eling W, Mazier D, , 2002. Effects of irradiation on Plasmodium falciparum sporozoite hepatic development: implications for the design of pre-erythrocytic malaria vaccines. Parasite Immunol 24: 221223.[Crossref] [Google Scholar]
  9. Hurtado S, Salas ML, Romero JF, Zapata JC, Ortiz H, Arévalo-Herrera M, Herrera S, , 1997. Regular production of infective sporozoites of Plasmodium falciparum and P. vivax in laboratory-bred Anopheles albimanus . Ann Trop Med Parasitol 91: 4960.[Crossref] [Google Scholar]
  10. Salas ML, Romero JF, Solarte Y, Olano V, Herrera MA, Herrera S, , 1994. Development of sporogonic cycle of Plasmodium vivax in experimentally infected Anopheles albimanus mosquitoes. Mem Inst Oswaldo Cruz 89 (Suppl 2): 115119.[Crossref] [Google Scholar]
  11. Arévalo-Herrera M, Solarte Y, Zamora F, Mendez F, Yasnot MF, Rocha L, Long C, Miller LH, Herrera S, , 2005. Plasmodium vivax: transmission-blocking immunity in a malaria-endemic area of Colombia. Am J Trop Med Hyg 73: 3843. [Google Scholar]
  12. Frederickson EC, , 1993. Bionomics and Control of Anopheles albimanus. Washington, DC: Pan-American Health Organization, 76. [Google Scholar]
  13. Rubio-Palis Y, , 2000. Anopheles (Nyssorhynchus) de Venezuela: Taxonomiìa, bionomiìa, ecologiìa e importancia meìdica. Maracay, Venezuela: Escuela Malariología y Saneamiento Ambiental. [Google Scholar]
  14. Rubio-Palis Y, Zimmerman RH, , 1997. Ecoregional classification of malaria vectors in the neotropics. J Med Entomol 34: 499510.[Crossref] [Google Scholar]
  15. Quiñones ML, , 1987. Estado de la susceptibilidad al DDT de los principales vectores de malaria en Colombia y su aplicación epidemiológica. Colombia Med 18: 1924. [Google Scholar]
  16. Vaughan JA, Noden BH, Beier JC, , 1994. Sporogonic development of cultured Plasmodium falciparum in six species of laboratory-reared Anopheles mosquitoes. Am J Trop Med Hyg 51: 233243. [Google Scholar]
  17. Collins WE, Warren M, Skinner JC, Richardson BB, Kearse TS, , 1977. Infectivity of the Santa Lucia (El Salvador) strain of Plasmodium falciparum to different anophelines. J Parasitol 63: 5761.[Crossref] [Google Scholar]
  18. Grieco JP, Achee NL, Roberts DR, Andre RG, , 2005. Comparative susceptibility of three species of Anopheles from Belize, Central America, to Plasmodium falciparum (NF-54). J Am Mosq Control Assoc 21: 279290.[Crossref] [Google Scholar]
  19. Collins WE, Warren M, Contacos PG, Skinner JC, Richardson BB, Kearse TS, , 1980. The Chesson strain of Plasmodium vivax in Aotus monkeys and anopheline mosquitoes. J Parasitol 66: 488497.[Crossref] [Google Scholar]
  20. Kiszewski A, Mellinger A, Spielman A, Malaney P, Sachs SE, Sachs J, , 2004. A global index representing the stability of malaria transmission. Am J Trop Med Hyg 70: 486498. [Google Scholar]
  21. Ramsey JM, Salinas E, Rodriguez MH, , 1996. Acquired transmission-blocking immunity to Plasmodium vivax in a population of southern coastal Mexico. Am J Trop Med Hyg 54: 458463. [Google Scholar]
  22. Herrera S, Fernandez O, Manzano MR, Murrain B, Vergara J, Blanco P, Palacios R, Velez JD, Epstein JE, Chen-Mok M, Reed ZH, Arévalo-Herrera M, , 2009. Successful sporozoite challenge model in human volunteers with Plasmodium vivax strain derived from human donors. Am J Trop Med Hyg 81: 740746.[Crossref] [Google Scholar]
  23. Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN, , 1993. 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. Mol Biochem Parasitol 58: 283292.[Crossref] [Google Scholar]
  24. Olano V, Carillo MP, Espinal CA, , 1985. Estudios de infectividad de la especie Anopheles albimanus Wiedemann, 1820 (Diptera: Culicidae) cepa Cartagena, con plasmodios humanos. Biomedica 5: 510.[Crossref] [Google Scholar]
  25. Graves PM, , 1980. Studies on the use of a membrane feeding technique for infecting Anopheles gambiae with Plasmodium falciparum . Trans R Soc Trop Med Hyg 74: 738742.[Crossref] [Google Scholar]
  26. Peters W, Ramkaran AE, , 1980. The chemotherapy of rodent malaria, XXXII. The influence of p-aminobenzoic acid on the transmission of Plasmodium yoelii and P. berghei by Anopheles stephensi . Ann Trop Med Parasitol 74: 275282.[Crossref] [Google Scholar]
  27. Eyles DE, , 1950. A stain for malarial oocysts in temporary preparations. J Parasitol 36: 501.[Crossref] [Google Scholar]
  28. Chulay JD, Schneider I, Cosgriff TM, Hoffman SL, Ballou WR, Quakyi IA, Carter R, Trosper JH, Hockmeyer WT, , 1986. Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum . Am J Trop Med Hyg 35: 6668. [Google Scholar]
  29. Kish L, , 1965. Survey Sampling. New York: John Wiley & Sons Inc. [Google Scholar]
  30. Herrera S, Solarte Y, Jordan A, Echavarria J, Rocha L, Palacios R, Ramirez O, Velez J, Epstein J, Richie T, Arévalo-Herrera M, , 2011. Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers. Am J Trop Med Hyg 84 (Suppl 2): 411.[Crossref] [Google Scholar]
  31. Sattabongkot J, Maneechai N, Rosenberg R, , 1991. Plasmodium vivax: gametocyte infectivity of naturally infected Thai adults. Parasitol 102: 2731.[Crossref] [Google Scholar]
  32. Rickman LS, Jones TR, Long GW, Paparello S, Schneider I, Paul CF, Beaudoin RL, Hoffman SL, , 1990. Plasmodium falciparum-infected Anopheles stephensi inconsistently transmit malaria to humans. Am J Trop Med Hyg 43: 441445. [Google Scholar]
  33. Gamage-Mendis AC, Rajakaruna J, Weerasinghe S, Mendis C, Carter R, Mendis KN, , 1993. Infectivity of Plasmodium vivax and P. falciparum to Anopheles tessellatus; relationship between oocyst and sporozoite development. Trans R Soc Trop Med Hyg 87: 36.[Crossref] [Google Scholar]
  34. Ponnudurai T, Lensen AH, van Gemert GJ, Bolmer MG, Meuwissen JH, , 1991. Feeding behaviour and sporozoite ejection by infected Anopheles stephensi . Trans R Soc Trop Med Hyg 85: 175180.[Crossref] [Google Scholar]
  35. Li X, Sina B, Rossignol PA, , 1992. Probing behaviour and sporozoite delivery by Anopheles stephensi infected with Plasmodium berghei . Med Vet Entomol 6: 5761.[Crossref] [Google Scholar]

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  • Received : 26 Aug 2009
  • Accepted : 24 Mar 2010
  • Published online : 04 Feb 2011

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