Volume 13 Supplement 1

Challenges in malaria research: Core science and innovation

Open Access

Controlled human malaria infection in Kenyan adults: A safe model that could accelerate assessment of novel drugs and vaccines in malaria endemic populations

  • Susanne Hodgson1,
  • Elizabeth Juma2,
  • Amina Salim3,
  • Charles Magiri2,
  • Domtila Kimani3,
  • Daniel Njenga2,
  • Alfred Muia2,
  • Andrew Cole2,
  • Caroline Ogwang3,
  • Peter Billingsley4,
  • Eric James4,
  • Kim Lee Sim4,
  • Thomas Rampling1,
  • Adrian Hill1,
  • Faith Osier3,
  • Simon Draper1,
  • Philip Bejon3,
  • Stephen Hoffman4,
  • Bernhards Ogutu2 and
  • Kevin Marsh3
Malaria Journal201413(Suppl 1):O33

https://doi.org/10.1186/1475-2875-13-S1-O33

Published: 22 September 2014

Background

Controlled human malaria infection (CHMI) studies, where healthy volunteers are infected with Plasmodium falciparum have become a vital tool to accelerate vaccine and drug development. As CHMI trials are carried out in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics and immunological responses to infection. Though commonly performed in malaria-naïve populations, CHMI trials have rarely been performed in malaria endemic regions, despite the advantages of early testing of candidate anti-malaria vaccines and drugs in populations where malaria is endemic. To date, modern CHMI studies have not been used to investigate mechanisms of naturally acquired immunity (NAI) to P. falciparum infection.

Materials and methods

We conducted an open label, randomized CHMI pilot study using aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) administered intramuscularly to evaluate safety, infectivity and parasite growth dynamics in healthy Kenyan adults (n = 28). We included adults with varying degrees of prior exposure to malaria in order to allow an evaluation of the effect of NAI on parasite growth dynamics post CHMI.

Results

All participants developed blood-stage infection, with a similar safety profile to that observed in northern CHMI centres. One volunteer remained asymptomatic and blood-film negative until day 21 post injection of PfSPZ Challenge, despite developing confirmed blood-stage infection by quantitative polymerase chain reaction (qPCR). This volunteer had a notably reduced parasite multiplication rate (1.3) in comparison to the other 27 volunteers (median 11.1). A significant correlation was seen between parasite multiplication rate (PMR) and anti-schizont ELISA OD at screening (P = 0.044).

Conclusions

Our study has shown that the PfSPZ Challenge is safe and infectious in malaria endemic populations and could be used to aid early assessment of the efficacy of candidate malaria vaccines and drugs in African populations. Whilst our findings are limited by sample size, our pilot study proves that NAI can impact on PMR post-CHMI in a detectable fashion. Our findings suggest the CHMI sporozoite model could allow identification of a heterogeneous group of participants with varying degrees of NAI for whom the relationship between PMR and candidate assays of blood-stage immunity can be examined to try to gain greater understanding of the mechanisms of NAI to P. falciparum malaria.

Declarations

Acknowledgements

This work was supported by the European and Developing Countries Clinical Trial Partnership, The National Institute of Allergy and Infectious Disease, The Wellcome Trust and the UK Medical Research Council.

Authors’ Affiliations

(1)
The Jenner Institute, University of Oxford
(2)
Kenyan Medical Research Institute
(3)
Kenyan Medical Research Insitute
(4)
Sanaria

Copyright

© Hodgson et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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