Experimental Challenge of Volunteers with Malaria

Editorials1 August 1997Experimental Challenge of Volunteers with MalariaStephen L. Hoffman, MD, DTMHStephen L. Hoffman, MD, DTMHNaval Medical Research Institute; Bethesda, MD 20889-5607Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-3-199708010-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail As physicians sworn to "do no harm" and clinical investigators working to develop malaria vaccines and drugs, my colleagues and I have had to repeatedly ask ourselves whether it is ethical to conduct experimental studies of malaria challenge in volunteers. We have discussed that question with members of human trial committees, volunteers, colleagues, and friends and family, many of whom have initially been incredulous to hear that persons volunteer to be infected with the parasites that cause malaria.Because malaria is a major threat to U.S. troops 1 and persons who travel abroad, the Department of Defense provides funding for ...References1. Beadle C, Hoffman SL. History of malaria in the United States Naval Forces at war: World War I through the Vietnam conflict. Clin Infect Dis. 1993; 16:320-9. Google Scholar2. World Health Organization. 1996 World Health Organization Fact Sheet N94 (revised). Malaria. Geneva: World Health Organization; 1996. Google Scholar3. Grassi B, Bignami A, Bastianelli G. Ulteriori ricerche sul ciclo dei parassiti malarici umani nel corpo del zanzarone. Atti Reale Accademia dei Lincei. 1899; 5:8-21. Google Scholar4. Fairley NH. Sidelights on malaria in man obtained by subinoculation experiments. Trans Royal Soc Trop Med Hyg. 1947; 40:621-76. Google Scholar5. Wagner-Juaregg. The treatment of general paresis by inoculation of malaria. J Nerv Ment Dis. 1922; 55:369-75. Google Scholar6. Hoffman SL, Miller LH. Perspectives on malaria vaccine development. In: Hoffmann SL, ed. Malaria Vaccine Development: A Multi-immune Response Approach. Washington, DC: The American Society for Microbiology; 1996:1-13. Google Scholar7. Chulay JD, Schneider I, Cosgriff TM, Hoffman SL, Ballou WR, Quakyi IA, et al. Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum. Am J Trop Med Hyg. 1986; 35:66-8. Google Scholar8. Herrington DA, Clyde DF, Murphy JR, Baqar S, Levine MM, do Rosario V, et al. A model for Plasmodium falciparum sporozoite challenge and very early therapy of parasitemia for efficacy studies of sporozoite vaccines Trop Geogr Med. 1988; 40:124-7. Google Scholar9. Church LW, Le TP, Bryan JP, Gordon DM, Edelman R, Fries *Illegible Text*. Clinical manifestations of Plasmodium falciparum malaria *Illegible Text* duced by mosquito challenge. J Infect Dis. 1997; 175:915-20. Google Scholar10. Ballou WR, Hoffman SL, Sherwood JA, Hollingdale MR, Neva FA, Hockmeyer WT, et al. Safety and immunogenicity of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet. 1987; 1:1277-81. Google Scholar11. Herrington D, Clyde DF, Losonsky G, Cortesia M, Murphy JR, Davis J, et al. Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature. 1987; 328:257-9. Google Scholar12. Malik A, Egan JE, Houghten RA, Sadoff JC, Hoffman SL. Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 1991; 88:3300-4. Google Scholar13. Egan JE, Hoffman SL, Haynes JD, Sadoff JL, Schneider I, Grau GE, et al. Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 1993; 49:166-73. Google Scholar14. Hoffman SL, Edelman R, Bryan JP, Davis J, Sedgah M, Gordon D, et al. Safety, immunogenicity and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant. Am J Trop Med Hyg. 1994; 51:603-12. Google Scholar15. Gordon DM, McGovern TW, Kryzch U, Cohen JC, Schneider I, LaChance R, et al. Safety, immunogenicity and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine. J Infect Dis. 1995; 171:1576-85. Google Scholar16. Stoute JA, Slaoui M, Heppner DG, Momin P, Kester KE, Desmons P, et al. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. N Engl J Med. 1997; 336:86-91. Google Scholar17. Shmuklarsky MJ, Boudreau EF, Pang LW, Smith JI, Schneider I, Fleckenstein L, et al. Failure of doxycycline as a causal prophylactic agent against Plasmodium falciparum malaria in healthy nonimmune volunteers. Ann *Illegible Text* Med. 1994; 120:294-9. Google Scholar18. Anderson SL, Berman J, Kuschner R, Wesche D, Magill A, Wellde B, et al. Prophylaxis of Plasmodium falciparum malaria with azithromycin adminstered to volunteers. Ann Intern Med. 1995; 123:771-3. Google Scholar19. Chen Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, Creasey A, et al. Measurement of Plasmodium falciparum growth rate in vivo: a test of malaria vaccines. Am J Trop Med Hyg. 1997; In press. Google Scholar20. Patarroyo ME, Amador R, Clavijo P, Moreno A, Guzman F, Romero P, et al. A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria. Nature. 1988; 332:158-61. Google Scholar Author, Article, and Disclosure InformationAffiliations: Naval Medical Research Institute; Bethesda, MD 20889-5607Grant Support: By Naval Medical Research and Development Command Work Units Nos. 61102A00101.BFX-1431 and 62787A00101.EFX-1432.Corresponding Author: Stephen L. Hoffman, MD, DTMH, Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607. 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