Experimentally induced blood-stage Plasmodium vivax infection in healthy volunteers.

BACKGROUND Major impediments to development of vaccines and drugs for Plasmodium vivax malaria are the inability to culture this species and the extreme difficulty in undertaking clinical research by experimental infection. METHODS A parasite bank was collected from a 49-year-old woman with P. vivax infection, characterized, and used in an experimental infection study. RESULTS The donor made a full recovery from malaria after collection of a parasite bank, which tested negative for agents screened for in blood donations. DNA sequence analysis of the isolate indicated that it was clonal. Two subjects inoculated with the isolate became polymerase chain reaction positive on days 8 and 9, with onset of symptoms and positive blood smears on day 14, when they were treated with artemether-lumefantrine, with rapid clinical and parasitologic response. Transcripts of the parasite gene pvs25 that is expressed in gametocytes, the life cycle stage infectious to mosquitoes, were first detected on days 11 and 12. CONCLUSIONS This experimental system results in in vivo parasite growth, probably infectious to mosquitoes. It offers the opportunity to undertake studies previously impossible in P. vivax that will facilitate a better understanding of the pathology of vivax malaria and development of antimalarial drugs and vaccines. Trial Registration. ANZCTR: 12612001096842.

[1]  S. Hoffman,et al.  Controlled Human Malaria Infections by Intradermal Injection of Cryopreserved Plasmodium falciparum Sporozoites , 2013, The American journal of tropical medicine and hygiene.

[2]  J. McCarthy,et al.  Experimentally induced blood stage malaria infection as a tool for clinical research. , 2012, Trends in parasitology.

[3]  D. Serre,et al.  Whole Genome Sequencing of Field Isolates Provides Robust Characterization of Genetic Diversity in Plasmodium vivax , 2012, PLoS neglected tropical diseases.

[4]  A. Dash,et al.  The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum , 2012, Nature Genetics.

[5]  John C. Tan,et al.  Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing , 2012, Nature.

[6]  R. Sauerwein,et al.  Comparison of Clinical and Parasitological Data from Controlled Human Malaria Infection Trials , 2012, PloS one.

[7]  S. Draper,et al.  Controlled human blood stage malaria infection: current status and potential applications. , 2012, The American journal of tropical medicine and hygiene.

[8]  Taane G. Clark,et al.  Characterization of Within-Host Plasmodium falciparum Diversity Using Next-Generation Sequence Data , 2012, PloS one.

[9]  L. Rénia,et al.  Cryopreserved Plasmodium vivax and cord blood reticulocytes can be used for invasion and short term culture. , 2012, International journal for parasitology.

[10]  E. R. James,et al.  Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity , 2011, Science.

[11]  Fellow,et al.  Therapeutic Guidelines: Antibiotic , 2011 .

[12]  D. Whiley,et al.  A real-time, quantitative PCR method using hydrolysis probes for the monitoring of Plasmodium falciparum load in experimentally infected human volunteers , 2011, Malaria Journal.

[13]  T. Richie,et al.  Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers. , 2011, The American journal of tropical medicine and hygiene.

[14]  R. Snow,et al.  Shrinking the malaria map: progress and prospects , 2010, Lancet.

[15]  Alejandro Llanos-Cuentas,et al.  Whole-genome sequencing and microarray analysis of ex vivo Plasmodium vivax reveal selective pressure on putative drug resistance genes , 2010, Proceedings of the National Academy of Sciences.

[16]  Adrian J F Luty,et al.  Protection against a malaria challenge by sporozoite inoculation. , 2009, The New England journal of medicine.

[17]  R. Sauerwein,et al.  Cardiac complication after experimental human malaria infection: a case report , 2009, Malaria Journal.

[18]  M. Chen-Mok,et al.  Successful sporozoite challenge model in human volunteers with Plasmodium vivax strain derived from human donors. , 2009, The American journal of tropical medicine and hygiene.

[19]  X. Su,et al.  Disruption of a Plasmodium falciparum Multidrug Resistance-associated Protein (PfMRP) Alters Its Fitness and Transport of Antimalarial Drugs and Glutathione , 2009, Journal of Biological Chemistry.

[20]  H. Fleury,et al.  Evaluation of FRET real-time PCR assay for rapid detection and differentiation of Plasmodium species in returning travellers and migrants , 2008, Malaria Journal.

[21]  Nicholas J White,et al.  Vivax malaria: neglected and not benign. , 2007, The American journal of tropical medicine and hygiene.

[22]  S. Hoffman,et al.  Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. , 2007, The Journal of infectious diseases.

[23]  C. Severini,et al.  Genetic variations of the Plasmodium vivax dihydropteroate synthase gene. , 2006, Acta tropica.

[24]  Q. Cheng,et al.  Limited Polymorphism in the Dihydropteroate Synthetase Gene (dhps) of Plasmodium vivax Isolates from Thailand , 2005, Antimicrobial Agents and Chemotherapy.

[25]  J. Baird,et al.  Novel Plasmodium vivax dhfr Alleles from the Indonesian Archipelago and Papua New Guinea: Association with Pyrimethamine Resistance Determined by a Saccharomyces cerevisiae Expression System , 2005, Antimicrobial Agents and Chemotherapy.

[26]  J. Baker,et al.  Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site , 2004, Antimicrobial Agents and Chemotherapy.

[27]  J. Roberts,et al.  A retrospective examination of the effect of fever and microgametocyte count on mosquito infection on humans infected with Plasmodium vivax. , 2004, The American journal of tropical medicine and hygiene.

[28]  M. Bangs,et al.  Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine. , 2004, The Journal of infectious diseases.

[29]  Momiao Xiong,et al.  Multiple transporters associated with malaria parasite responses to chloroquine and quinine , 2003, Molecular microbiology.

[30]  K. Kotloff.  Human challenge studies with infectious agents. , 2003, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[31]  J. Kublin,et al.  Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. , 2002, The Journal of infectious diseases.

[32]  F G Miller,et al.  The ethical challenge of infection-inducing challenge experiments. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[33]  K. Kirk,et al.  Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum , 2000, Nature.

[34]  D. Kaslow,et al.  Sequence Polymorphism in Two Novel Plasmodium vivax Ookinete Surface Proteins, Pvs25 and Pvs28, That Are Malaria Transmission-blocking Vaccine Candidates , 1998, Molecular medicine.

[35]  Q. Cheng,et al.  Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines. , 1997, The American journal of tropical medicine and hygiene.

[36]  Richard G Kimber,et al.  The Australian Red Cross Blood Service , 1997, The Medical journal of Australia.

[37]  S L Hoffman,et al.  Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. , 1997, The Journal of infectious diseases.

[38]  W. Trager,et al.  Human malaria parasites in continuous culture. , 1976, Science.

[39]  K. Rieckmann,et al.  Mefloquine (WR 142,490) in the treatment of human malaria , 1975, Science.

[40]  C. B. Evans,et al.  Fluorescent antibody studies on the immune response in sporozoite-induced and blood-induced vivax malaria and the relationship of antibody production to parasitemia. , 1966, The American journal of tropical medicine and hygiene.

[41]  S. Kitchen,et al.  On Attempts to hyperimmunize Convalescents from Vivax Malaria. , 1943 .

[42]  G. Snounou,et al.  Malariotherapy--insanity at the service of malariology. , 2013, Advances in parasitology.

[43]  R. Sauerwein,et al.  Experimental human challenge infections can accelerate clinical malaria vaccine development , 2010, Nature Reviews Immunology.

[44]  S. Hoffman,et al.  Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum. , 1986, The American journal of tropical medicine and hygiene.

[45]  Additional standards for human blood and blood products, source plasma (human); amendment of storage temperature requirements: Food and Drug Administration, Final rule. , 1980, Federal register.