Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya.
BACKGROUND
Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. However, to date few modern CHMI studies have been performed in malaria-endemic countries.


METHODS
An open-label, randomized pilot CHMI study was conducted using aseptic, purified, cryopreserved, infectious P. falciparum sporozoites (SPZ) (Sanaria® PfSPZ Challenge) administered intramuscularly (IM) to healthy Kenyan adults (n = 28) with varying degrees of prior exposure to P. falciparum. The purpose of the study was to establish the PfSPZ Challenge CHMI model in a Kenyan setting with the aim of increasing the international capacity for efficacy testing of malaria vaccines and drugs, and allowing earlier assessment of efficacy in a population for which interventions are being developed. This was part of the EDCTP-funded capacity development of the CHMI platform in Africa.


CONCLUSIONS
This paper discusses in detail lessons learnt from conducting the first CHMI study in Kenya. Issues pertinent to the African setting, including community sensitization, consent and recruitment are considered. Detailed reasoning regarding the study design (for example, dose and route of administration of PfSPZ Challenge, criteria for grouping volunteers according to prior exposure to malaria and duration of follow-up post CHMI) are given and changes other centres may want to consider for future studies are suggested.


CONCLUSIONS
Performing CHMI studies in an African setting presents unique but surmountable challenges and offers great opportunity for acceleration of malaria vaccine and drug development. The reflections in this paper aim to aid other centres and partners intending to use the CHMI model in Africa.
The Jenner Institute, University of Oxford, Oxford, UK. Susanne.hodgson@ndm.ox.ac.uk.
Susanne H
SH
Hodgson
Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. eajuma@kemri.org.|Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya. eajuma@kemri.org.
Elizabeth
E
Juma
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. asalim@kemri-wellcome.org.
Amina
A
Salim
Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. charles.magiri@usamru-k.org.
Charles
C
Magiri
Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. danielnjengah@yahoo.com.
Daniel
D
Njenga
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. smolyneux@kemri-wellcome.org.
Sassy
S
Molyneux
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. patwnju@yahoo.co.uk.
Patricia
P
Njuguna
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. kawuondo@kemri-wellcome.org.
Ken
K
Awuondo
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. blowe@kemri-wellcome.org.
Brett
B
Lowe
Sanaria Inc, Rockville, MD, USA. pbillingsley@sanaria.com.
Peter F
PF
Billingsley
Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. omandi.cole@gmail.com.|Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya. omandi.cole@gmail.com.
Andrew O
AO
Cole
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. COgwang@kemri-wellcome.org.
Caroline
C
Ogwang
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. fosier@kemri-wellcome.org.
Faith
F
Osier
Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Roma.Chilengi@cidrz.org.
Roma
R
Chilengi
Sanaria Inc, Rockville, MD, USA. shoffman@sanaria.com.
Stephen L
SL
Hoffman
The Jenner Institute, University of Oxford, Oxford, UK. simon.draper@ndm.ox.ac.uk.
Simon J
SJ
Draper
Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. bernhards.ogutu@indepth-network.org.|Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya. bernhards.ogutu@indepth-network.org.
Bernhards
B
Ogutu
Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. kevin.marsh@ndm.ox.ac.uk.
Kevin
K
Marsh
D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007630:Kenya; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D010865:Pilot Projects; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D034101:Sporozoites / Q000254:growth & development / Q000276:immunology*; D055815:Young Adult