Lack of Molecular Correlates of Plasmodium vivax Ookinete Development

Viengngeun Bounkeua Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Viengngeun Bounkeua in
Current site
Google Scholar
PubMed
Close
,
Fengwu Li Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Fengwu Li in
Current site
Google Scholar
PubMed
Close
,
Raul Chuquiyauri Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Raul Chuquiyauri in
Current site
Google Scholar
PubMed
Close
,
Shira R. Abeles Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Shira R. Abeles in
Current site
Google Scholar
PubMed
Close
,
Colleen M. McClean Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Colleen M. McClean in
Current site
Google Scholar
PubMed
Close
,
Victor Neyra Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Victor Neyra in
Current site
Google Scholar
PubMed
Close
,
Alejandro Llanos-Cuentas Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Alejandro Llanos-Cuentas in
Current site
Google Scholar
PubMed
Close
,
Pablo P. Yori Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Pablo P. Yori in
Current site
Google Scholar
PubMed
Close
, and
Joseph M. Vinetz Department of Medicine, University of California San Diego, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Search for other papers by Joseph M. Vinetz in
Current site
Google Scholar
PubMed
Close
Restricted access

Previous studies of Plasmodium vivax transmission to Anopheles spp. mosquitoes have not been able to predict mosquito infectivity on the basis of microscopic or molecular quantification of parasites (total parasites in the sample or total number of gametocytes) in infected blood. Two methods for production of P. vivax ookinete cultures in vitro, with yields of 106 macrogametocytes, 104 zygotes, and 103 ookinetes, respectively, per 10 mL of P. vivax-infected patient blood with approximately 0.01% parasitemia, were used to study P. vivax sexual stage development. The quantity of gametocytes, determined by counting Giemsa-stained blood smears, and quantity and type of gametocyte as determined by quantitative reverse transcriptase–polymerase chain reaction for Pvalpha tubulin II and macrogametocyte-specific pvg377 did not predict ookinete yield. Factors that affect the efficiency of in vitro P. vivax ookinete transformation remain poorly understood.

Author Notes

*Address correspondence to Joseph M. Vinetz, Division of Infectious Diseases, Department of Medicine, University of California San Diego, 9500 Gilman Drive 0741, George Palade Laboratories Room 125, La Jolla, CA 92093. E-mail: jvinetz@ucsd.edu
†These authors contributed equally to this article.

Financial support: This study was supported by U.S. Public Health Service grants T32GM007198, K24AI068903, R01AI45999, U19AI089681, R01AI067727, and D43TW007120, and the Medicines for Malaria Venture, Geneva, Switzerland.

Disclosure: None of the authors have any conflicts of interest.

Authors' addresses: Viengngeun Bounkeua, Fengwu Li, Shira R. Abeles, and Colleen M. McClean, Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, E-mails: vbounkeua@ucsd.edu, f1li@ucsd.edu, sabeles@ucsd.edu, and mmcclean@gmail.com. Raul Chuquiyauri and Joseph M. Vinetz, Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA and Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mails: jvinetz@ucsd.edu and rachuqui@ucsd.edu. Victor Neyra and Alejandro Llanos-Cuentas, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mails: victorneyra2002@yahoo.es and elmer.llanos@upch.pe. Pablo P. Yori, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: pyori@jhsph.edu.

  • 1.

    Mendis KN, 2001. The neglected burden of P. vivax malaria. Am J Trop Med Hyg 164: 97106.

  • 2.

    Guerra CA, Snow RW, Hay SI, 2006. Mapping the global extent of malaria in 2005. Trends Parasitol 22: 353358.

  • 3.

    Hay SI, Guerra CA, Tatem AJ, Noor AM, Snow RW, 2004. The global distribution and population at risk of malaria: past, present, and future. Lancet Infect Dis 4: 327336.

    • Search Google Scholar
    • Export Citation
  • 4.

    Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM, 2007. Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77: 7987.

  • 5.

    Branch O, Casapia WM, Gamboa DV, Hernandez JN, Alava FF, Roncal N, Alvarez E, Perez EJ, Gotuzzo E, 2005. Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community. Malar J 4: 27.

    • Search Google Scholar
    • Export Citation
  • 6.

    Roshanravan B, Kari E, Gilman RH, Cabrera L, Lee E, Metcalfe J, Calderon M, Lescano AG, Montenegro-James S, Calampa C, Vinetz JM, 2003. Endemic malaria in the Peruvian Amazon region of Iquitos. Am J Trop Med Hyg 69: 4552.

    • Search Google Scholar
    • Export Citation
  • 7.

    Zollner GE, Ponsa N, Garman GW, Poudel S, Bell JA, Sattabongkot J, Coleman RE, Vaughan JA, 2006. Population dynamics of sporogony for Plasmodium vivax parasites from western Thailand developing within three species of colonized Anopheles mosquitoes. Malar J 5: 68.

    • Search Google Scholar
    • Export Citation
  • 8.

    Saul A, 1992. Towards a malaria vaccine: riding the rollercoaster between unrealistic optimism and lethal pessimism. Southeast Asian J Trop Med Public Health 23: 656671.

    • Search Google Scholar
    • Export Citation
  • 9.

    Saul A, 2007. Mosquito stage, transmission blocking vaccines for malaria. Curr Opin Infect Dis 20: 476481.

  • 10.

    Gwadz RW, 1976. Successful immunization against the sexual stages of Plasmodium gallinaceum. Science 193: 11501151.

  • 11.

    Lavazec C, Bourgouin C, 2008. Mosquito-based transmission blocking vaccines for interrupting Plasmodium development. Microbes Infect 10: 845849.

    • Search Google Scholar
    • Export Citation
  • 12.

    Suwanabun N, Sattabongkot J, Tsuboi T, Torii M, Maneechai N, Rachapaew N, Yim-amnuaychok N, Punkitchar V, Coleman RE, 2001. Development of a method for the in vitro production of Plasmodium vivax ookinetes. J Parasitol 87: 928930.

    • Search Google Scholar
    • Export Citation
  • 13.

    McClean CM, Alvarado HG, Neyra V, Llanos-Cuentas A, Vinetz JM, 2010. Optimized in vitro production of Plasmodium vivax ookinetes. Am J Trop Med Hyg 83: 11831186.

    • Search Google Scholar
    • Export Citation
  • 14.

    Eyles DE, Young MD, Burgess RW, 1948. Studies on imported malarias; infectivity to Anopheles quadrimaculatus of asymptomatic Plasmodium vivax parasitemias. J Natl Malar Soc 7: 125133.

    • Search Google Scholar
    • Export Citation
  • 15.

    Bharti AR, Chuquiyauri R, Brouwer KC, Stancil J, Lin J, Llanos-Cuentas A, Vinetz JM, 2006. Experimental infection of the neotropical malaria vector Anopheles darlingi by human patient-derived Plasmodium vivax in the Peruvian Amazon. Am J Trop Med Hyg 75: 610616.

    • Search Google Scholar
    • Export Citation
  • 16.

    Al-Olayan EM BA, Butcher GA, Sinden RE, Hurd H, 2002. Complete development of mosquito phases of the malaria parasite in vitro. Science 295: 677679.

    • Search Google Scholar
    • Export Citation
  • 17.

    Westenberger SJ, McClean CM, Chattopadhya R, Dharia NV, Carlton JM, Barnwell JW, Collins WE, Hoffman SL, Zhou Y, Vinetz JM, Winzeler EA, 2010. A systems-based analysis of Plasmodium vivax lifecycle transcription from human to mosquito. PLoS Negl Trop Dis 4: e653. doi:10.1371/journal.pntd.0000653.

    • Search Google Scholar
    • Export Citation
  • 18.

    Rawlings DJ, Fujioka H, Fried M, Keister DB, Aikawa M, Kaslow DC, 1992. Alpha-tubulin II is a male-specific protein in Plasmodium falciparum. Mol Biochem Parasitol 56: 239250.

    • Search Google Scholar
    • Export Citation
  • 19.

    Babiker HA, Abdel-Wahab A, Ahmed S, Suleiman S, Ranford-Cartwright L, Carter R, Walliker D, 1999. Detection of low level Plasmodium falciparum gametocytes using reverse transcriptase polymerase chain reaction. Mol Biochem Parasitol 99: 143148.

    • Search Google Scholar
    • Export Citation
  • 20.

    Hisaeda H, Stowers AW, Tsuboi T, Collins WE, Sattabongkot JS, Suwanabun N, Torii M, Kaslow DC, 2000. Antibodies to malaria vaccine candidates Pvs25 and Pvs28 completely block the ability of Plasmodium vivax to infect mosquitoes. Infect Immun 68: 66186623.

    • Search Google Scholar
    • Export Citation
  • 21.

    Billker O, Lindo V, Panico M, Etienne AE, Paxton T, Dell A, Rogers M, Sinden RE, Morris HR, 1998. Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature 392: 289292.

    • Search Google Scholar
    • Export Citation
  • 22.

    Billker O, Miller AJ, Sinden RE, 2000. Determination of mosquito bloodmeal pH in situ by ion-selective microelectrode measurement: implications for the regulation of malarial gametogenesis. Parasitology 120 (Pt 6): 547551.

    • Search Google Scholar
    • Export Citation
  • 23.

    Garcia GE, Wirtz RA, Barr JR et al., 1998. Xanthurenic acid induces gametogenesis in Plasmodium, the malaria parasite. The Journal of Biological Chemistry 273: 20.

    • Search Google Scholar
    • Export Citation
  • 24.

    Muhia DK, Swales CA, Deng W, Kelly JM, Baker DA, 2001. The gametocyte-activating factor xanthurenic acid stimulates an increase in membrane-associated guanylyl cyclase activity in the human malaria parasite Plasmodium falciparum. Mol Microbiol 42: 553560.

    • Search Google Scholar
    • Export Citation
  • 25.

    McRobert L, Taylor CJ, Deng W, Fivelman QL, Cummings RM, Polley SD, Billker O, Baker DA, 2008. Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase. PLoS Biol 6: e139.

    • Search Google Scholar
    • Export Citation
  • 26.

    Eyles DE, 1948. Anopheles mosquito production of the plant communities of Reelfoot Lake. J Tenn Acad Sci 23: 139147.

  • 27.

    Nicastri E, Bevilacqua N, Sane Schepisi M, Paglia MG, Meschi S, Ame SM, Mohamed JA, Mangi S, Fumakule R, Di Caro A, Capobianchi MR, Kitua A, Molteni F, Racalbuto V, Ippolito G, 2009. Accuracy of malaria diagnosis by microscopy, rapid diagnostic test, and PCR methods and evidence of antimalarial overprescription in non-severe febrile patients in two Tanzanian hospitals. Am J Trop Med Hyg 80: 712717.

    • Search Google Scholar
    • Export Citation
  • 28.

    Guinet F, Dvorak J, Fujioka H, Keister D, Muratova O, Kaslow D, Aikawa M, Vaidya A, Wellems T, 1996. A development defect in Plasmodium falciparum male gametogenesis. Journal of Cell Biology 135: 269278.

    • Search Google Scholar
    • Export Citation
  • 29.

    Carter R, Ranford-Cartwright L, Alano P, 1993. The culture and preparation of gametocytes of Plasmodium falciparum for immunochemical, molecular, and mosquito infectivity studies. Methods Mol Biol 21: 6788.

    • Search Google Scholar
    • Export Citation
  • 30.

    Arai M, Billker O, Morris HR, Panico M, Delcroix M, Dixon D, Ley SV, Sinden RE, 2001. Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate gametogenesis of Plasmodium in the midgut of the mosquito. Mol Biochem Parasitol 116: 1724.

    • Search Google Scholar
    • Export Citation
  • 31.

    Naotunne TDS, Karunaweera ND, Giudice GD, Kularatne MU, Grau GE, Carter R, Mendis KN, 1991. Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential. J Exp Med 173: 523529.

    • Search Google Scholar
    • Export Citation
  • 32.

    Karunaweera ND, Carter R, Grau GE, Kwiatkowski D, Del Giudice G, Mendis KN, 1992. Tumour necrosis factor-dependent parasite-killing effects during paroxysms in non-immune Plasmodium vivax malaria patients. Clin Exp Immunol 88: 499505.

    • Search Google Scholar
    • Export Citation
  • 33.

    Karunaweera ND, Grau GE, Gamage P, Carter R, Mendis KN, 1992. Dynamics of fever and serum levels of tumor necrosis factor are closely associated during clinical paraxysms in Plasmodium vivax malaria. Proc Natl Acad Sci USA 89: 32003203.

    • Search Google Scholar
    • Export Citation
  • 34.

    Huh AJ, Kwak YG, Kim ES, Lee KS, Yeom JS, Cho YK, Kim CS, Park JW, 2011. Parasitemia characteristics of Plasmodium vivax malaria patients in the Republic of Korea. J Korean Med Sci 26: 4246.

    • Search Google Scholar
    • Export Citation
  • 35.

    Reece SE, Duncan AB, West SA, Read AF, 2003. Sex ratios in the rodent malaria parasite, Plasmodium chabaudi. Parasitology 127: 419425.

  • 36.

    Drew DR, Reece SE, 2007. Development of reverse-transcription PCR techniques to analyse the density and sex ratio of gametocytes in genetically diverse Plasmodium chabaudi infections. Mol Biochem Parasitol 156: 199209.

    • Search Google Scholar
    • Export Citation
  • 37.

    Babiker HA, Schneider P, Reece SE, 2008. Gametocytes: insights gained during a decade of molecular monitoring. Trends Parasitol 24: 525530.

  • 38.

    Schwank S, Sutherland CJ, Drakeley CJ, 2010. Promiscuous expression of alpha-tubulin II in maturing male and female Plasmodium falciparum gametocytes. PLoS One 5: e14470.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 26 26 7
Full Text Views 349 100 0
PDF Downloads 89 30 0
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save