2012
DOI: 10.4269/ajtmh.2012.11-0504
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Controlled Human Blood Stage Malaria Infection: Current Status and Potential Applications

Abstract: Abstract. Controlled human malaria infection by blood stage parasite (BSP) inoculation is an alternative to the wellestablished model of infection with Plasmodium falciparum sporozoites delivered by mosquito bites. The BSP model has been utilized less frequently, but its use is increasing. Advantages of BSP challenge include greater ease of administration, better standardization of the infecting dose per volunteer, and good inter-study reproducibility of in vivo parasite dynamics. Recently, a surprising reduct… Show more

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Cited by 47 publications
(44 citation statements)
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“…This is an important measure of the reproducibility of the model. The use of the highly sensitive qPCR to monitor parasitemia pretreatment as well as the clearance post antimalarial treatment, not only ensures subject safety, but also allows accurate calculation of the parasite growth rate and PMR [33]. Interestingly, there was not a substantial difference in the parasite growth rate and PMR between cohorts, including cohorts conducted in the P .…”
Section: Discussionmentioning
confidence: 99%
“…This is an important measure of the reproducibility of the model. The use of the highly sensitive qPCR to monitor parasitemia pretreatment as well as the clearance post antimalarial treatment, not only ensures subject safety, but also allows accurate calculation of the parasite growth rate and PMR [33]. Interestingly, there was not a substantial difference in the parasite growth rate and PMR between cohorts, including cohorts conducted in the P .…”
Section: Discussionmentioning
confidence: 99%
“…In diseases such as malaria, human challenge is permitted and can be conducted at a defined time point following immunization (1). For some infectious diseases such as HIV, live human challenge is unethical, so protection is determined through reduced incidence of disease in a susceptible population (2).…”
mentioning
confidence: 99%
“…Another Phase I/IIa study with recombinant AMA1 delivered in the adjuvants AS01 B and AS02 A also did not show sterilising protection after sporozoite CHMI, but parasite densities seemed to be reduced as estimated from qPCR data (Spring et al, 2009), again suggestive of a possible effect of anti-AMA1 responses at the preerythrocytic stage. A more recent Phase IIa trial of the same vaccine in AS01 B also failed to show any impact on blood-stage PMR of vaccine homologous parasites, following use of the more sensitive blood-stage CHMI model (NCT02044198) (Duncan and Draper, 2012;Sheehy et al, 2013a). Intriguingly, however, this AMA1/AS02 A vaccine was reported to exhibit strain-specific protection in a Phase IIb field trial in Malian children, suggesting efficacy may only be apparent in the context of other naturally acquired responses (Thera et al, 2011).…”
Section: Blood-stage Subunit Vaccinesmentioning
confidence: 87%