Dow GS, Magill AJ, Ohrt C, 2008. Clinical development of new prophylactic antimalarial drugs after the 5th Amendment to the Declaration of Helsinki. Ther Clin Risk Manag 4: 803–819.
Lyon JA, Angov E, Fay MP, Sullivan JS, Girourd AS, Robinson SJ, Bermann-Leitner ES, Duncan EH, Darko CA, Collins WE, Long CA, Barnwell JW, 2008. Protection induced by Plasmodium falciparum MSP142 is strain-specific, antigen and adjuvant dependent, and correlates with antibody responses. PLoS One 3: e2830.
Hui G, Hashimoto C, 2006. Plasmodium falciparum anti-MSP1-19 antibodies induced by MSP1-42 and MSP1-19 based vaccines differed in specificity and parasite growth inhibition in terms of recognition of conserved versus variant epitopes. Vaccine 25: 948–956.
Drakeley CJ, Corran PH, Coleman PG, Tongren JE, McDonald SLR, Carneiro I, Malima R, Lusingu J, Manjurano A, Nkya WMMM, Lemnge MM, Cox J, Reyburn H, Riley EM, 2005. Estimating medium- and long-term trends in malaria transmission by using serological markers of malaria exposure. Proc Natl Acad Sci USA 102: 5108–5113.
Roche USA, 2009. Lariam (Mefloquine Hydrochloride) Tablets Product Information. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed November 23, 2010.
Clyde DF, McCarthy VC, Miller RM, Hornick RB, 1976. Suppressive activity of mefloquine in sporozoite-induced human malaria. Antimicrob Agents Chemother 9: 384–386.
Bwire R, Slootman EJH, Verhave JP, Bruins J, Docters van Leeuwen WM, 1998. Malaria anticircumsporozoite antibodies in Dutch soldiers returning from sub-Saharan Africa. Trop Med Int Health 3: 66–69.
Boudreau E, Schuster B, Sanchez J, Novakowski W, Johnson R, Redmond D, Hanson R, Dausel L, 1993. Tolerability of prophylactic Lariam regimens. Trop Med Parasitol 44: 257–265.
Hopperus Buma APCC, van Thiel PPAM, Lobel HO, Ohrt C, van Ameijden EJC, Veltnik RL, Tendeloo DCH, van Gool T, Green MD, Todd GD, Kyle DE, Kager PA, 1996. Long-term malaria chemoprophylaxis with mefloquine in Dutch marines in Cambodia. J Infect Dis 173: 1506–1509.
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: 66–68.
Federal Regulations, 2010. 21 CFR 312.32: IND Safety Reports. Text from Code of Federal Regulations. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. Accessed November 23, 2010.
Yoon I, Angov E, Larson D, Heppner DG, Cummings JF, Stewart VA, 2005. Characterization of a human reference standard for antibody to Plasmodium falciparum merozoite surface protein 142. Am J Trop Med Hyg 72: 714–718.
Green MD, Yngve B, Mount DL, Corbett S, D'Souza MJ, 1999. Improved validated assay for the determination of mefloquine and its carboxy metabolite in plasma, serum and whole blood using solid-phase extraction and high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 727: 159–165.
Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC, 1993. Long-term malaria prophylaxis with weekly mefloquine. Lancet 34: 848–851.
|Past two years||Past Year||Past 30 Days|
|Full Text Views||291||86||2|
A sensitive biomarker of malaria infection would obviate the need for placebo control arms in clinical trials of malaria prophylactic drugs. Antibodies to the 42-kDa fragment of merozoite surface protein-1 (MSP142) have been identified as a potential marker of malaria exposure in individuals receiving prophylaxis with mefloquine. We conducted an open-label trial to determine the sensitivity of seroconversion to MSP142, defined as a fourfold rise in enzyme-linked immunosorbant assay (ELISA) titer, among 23 malaria naïve volunteers receiving mefloquine prophylaxis and 6 controls after Plasmodium falciparum sporozoite challenge. All members of the control cohort but none of the mefloquine cohort developed patent parasitemia. Four of six controls but zero of the mefloquine cohort seroconverted to MSP142. We conclude that malaria infection during suppressive prophylaxis does not induce antibody response to the blood-stage antigen MSP142 in a malaria-naïve study population.
Financial support: This project was supported by the United States Army Medical Materiel Development Activity.
Authors' addresses: James E. Moon, Gregory A. Deye, Lori Miller, Susan Fracisco, R. Scott Miller, Donna Tosh, James F. Cummings, Colin Ohrt, and Alan J. Magill, Walter Reed Army Institute of Research, Silver Spring, MD, E-mails: firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, and firstname.lastname@example.org.