title: Evaluating controlled human malaria infection in Kenyan adults with varying degrees of prior exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection.
abstract: BACKGROUND
  Controlled human malaria infection (CHMI) studies are a vital tool to accelerate vaccine and drug development. As CHMI trials are performed in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics (PGD) and immunological responses. However, CHMI studies have not been routinely performed in malaria-endemic countries or used to investigate mechanisms of naturally-acquired immunity (NAI) to Plasmodium falciparum.
  
  
  METHODS
  We conducted an open-label, randomized CHMI pilot-study using aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) to evaluate safety, infectivity and PGD in Kenyan adults with low to moderate prior exposure to P. falciparum (Pan African Clinical Trial Registry: PACTR20121100033272).
  
  
  RESULTS
  All participants developed blood-stage infection confirmed by quantitative polymerase chain reaction (qPCR). However one volunteer (110) remained asymptomatic and blood-film negative until day 21 post-injection of PfSPZ Challenge. This volunteer had a reduced parasite multiplication rate (PMR) (1.3) in comparison to the other 27 volunteers (median 11.1). A significant correlation was seen between PMR and screening anti-schizont Enzyme Linked Immunosorbent Assays (ELISA) OD (p = 0.044, R = -0.384) but not when volunteer 110 was excluded from the analysis (p = 0.112, R = -0.313).
  
  
  CONCLUSIONS
  PfSPZ Challenge is safe and infectious in malaria-endemic populations and could be used to assess the efficacy of malaria vaccines and drugs in African populations. Whilst our findings are limited by sample size, our pilot study has demonstrated for the first time that NAI may impact on PMR post-CHMI in a detectable fashion, an important finding that should be evaluated in further CHMI studies.
authors.affiliation: The Jenner Institute, University of Oxford Oxford, UK.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Hodgson
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute Nairobi, Kenya ; Centre for Research in Therapeutic Sciences, Strathmore University Nairobi, Kenya.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Juma
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Amina
authors.initials: A
authors.lastname: Salim
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute Nairobi, Kenya.
authors.forename: Charles
authors.initials: C
authors.lastname: Magiri
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Domtila
authors.initials: D
authors.lastname: Kimani
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute Nairobi, Kenya.
authors.forename: Daniel
authors.initials: D
authors.lastname: Njenga
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute Nairobi, Kenya.
authors.forename: Alfred
authors.initials: A
authors.lastname: Muia
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute Nairobi, Kenya ; Centre for Research in Therapeutic Sciences, Strathmore University Nairobi, Kenya.
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Cole
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ogwang
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Ken
authors.initials: K
authors.lastname: Awuondo
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Brett
authors.initials: B
authors.lastname: Lowe
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Marianne
authors.initials: M
authors.lastname: Munene
authors.affiliation: Sanaria Inc. Rockville, MD, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Billingsley
authors.affiliation: Sanaria Inc. Rockville, MD, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: James
authors.affiliation: Sanaria Inc. Rockville, MD, USA.
authors.forename: Anusha
authors.initials: A
authors.lastname: Gunasekera
authors.affiliation: Sanaria Inc. Rockville, MD, USA.
authors.forename: B Kim L
authors.initials: BK
authors.lastname: Sim
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Patricia
authors.initials: P
authors.lastname: Njuguna
authors.affiliation: The Jenner Institute, University of Oxford Oxford, UK.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Rampling
authors.affiliation: Sanaria Inc. Rockville, MD, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Richman
authors.affiliation: Sanaria Inc. Rockville, MD, USA.
authors.forename: Yonas
authors.initials: Y
authors.lastname: Abebe
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Gathoni
authors.initials: G
authors.lastname: Kamuyu
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Michelle
authors.initials: M
authors.lastname: Muthui
authors.affiliation: The Jenner Institute, University of Oxford Oxford, UK.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Elias
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Sassy
authors.initials: S
authors.lastname: Molyneux
authors.affiliation: Centre for Statistics in Medicine, University of Oxford Oxford, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gerry
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Alex
authors.initials: A
authors.lastname: Macharia
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya ; Department of Medicine, Imperial College London London, UK.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Bull
authors.affiliation: The Jenner Institute, University of Oxford Oxford, UK.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Faith H
authors.initials: FH
authors.lastname: Osier
authors.affiliation: The Jenner Institute, University of Oxford Oxford, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.affiliation: Sanaria Inc. Rockville, MD, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute Nairobi, Kenya ; Centre for Research in Therapeutic Sciences, Strathmore University Nairobi, Kenya.
authors.forename: Bernhards
authors.initials: B
authors.lastname: Ogutu
authors.affiliation: Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute - Wellcome Trust Kilifi, Kenya.
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
keywords: CHMI; challenge; falciparum; immunity; malaria